1What processes are involved in hematopoiesis?
renewal, proliferation, differentiation, and maturation of all blood cell lines
2What is the outcome of hematopoiesis?
formation, development, and specialization of all functional blood cells that are released from bone marrow into circulation
3What are the 3 phases of hematopoiesis?
"1. mesoblastic
2. hepatic
3. medullary"
4Where does mesoblastic hematopoiesis take place?
yolk sac and AGM
5What does AGM stand for?
aorta-gonad-mesonephros
6Where does hepatic hematopoiesis take place?
liver and spleen
7Where does medullary hematopoiesis take place?
bone marrow
8What is the age of development for mesoblastic phase?
9th day after fertilization
9What is the site of hematopoiesis during the mesoblastic phase?
cells from mesoderm migrate to yolk sac to make primitive erythroblasts
10Is mesoblastic phase erythropoiesis intravascular or extravascular?
intravascular
11What are the types of hemoglobin present in mesoblastic phase?
"embryonic hemoglobins:
Gower I, Gower II, Portland"
12What is the age of development for hepatic phase?
begins at 5-7 gestational weeks
13Is hepatic phase erythropoiesis extra- or intravascular?
extravascular
14What is the major hematopoietic organ during the second trimester of the hepatic phase?
liver
15What are the types of cells present in the hepatic phase?
recognizable clusters of developing erythroblasts, granulocytes, and monocytes
16What are the types of hemoglobin present in hepatic phase?
"mainly HbF, small amt of HbA development
(HbF = fetal hemoglobin)"
17What age is peak hematopoiesis for hepatic phase?
3rd month of fetal development
18What organs contribute to the hepatic phase?
thymus (t cells), spleen and kidney (b cells)
19What is the age of development for medullary phase?
begins between the 4th and 5th month of fetal development
20What is the site of hematopoiesis during the medullar phase? (what happens during medullar phase)
"HSC and mesenchymal cells migrate to core of bone,
mesenchymal produce stromal cells
myeloid development is apparent
by wk 24, BM is primary hematopoietic site"
21What do mesenchymal cells do when they migrate to core of bone during medullar phase?
mesenchymal cells produce stromal cells that support developing hematopoietic cells
22What happens to the myeloid-to-erythroid (M:E) ratio during medullary stage?
(M:E) of 3:1 to 4:1 (normal adult levels)
23What are the types of hemoglobin present in medullary phase?
HbF and HbA
24What are important growth factors and cytokines in medullary phase?
"Erythropoietin (EPO)
granulocyte colony-stimulating factor (G-CSF)
granulocyte-mq colony stimulating factor (GM-CSF)"
25What are and tissues and involved in adult hematopoietic tissue?
"bone marrow
lymph nodes
spleen, liver
thymus"
26What is the myeloid development in adult hematopoietic tissue?
erythroid, myeloid, megakaryocytic, and lymphoid cells develop in the BM
27What are the 2 categories of organs involved in lymphoid development of adult hematopoietic tissue?
"primary lymphoid organ
secondary lymphoid organ"
28What organs are in the primary lymphoid organ?
"BM for T cells and B cells,
thymus for T cell development"
29What organs are in the secondary lymphoid organ?
"spleen
lymph nodes,
mucosa-associated lymphoid tissue (MALT)"
30What is the bone marrow structure?
trabecular radiate out from the cortex into central cavity forming honeycomb structure
31What is the red marrow of BM?
haematopoietically active marrow
32What kind of bones are red marrow in infancy and childhood?
all bones
33What happens to bone marrow by age 4?
"adipocytes increase in number
(adding yellow marrow to what was previously all red)"
34What is yellow marrow?
"haematopoietically Inactive marrow
mostly fat cells or adipocytes"
35What is marrow cellularity in BM?
ratio of red to yellow marrow will decrease with age
36What is the estimate BM cellularity if a patient is <50 years old?
hypOcellular
37What is the estimate BM cellularity if a pt is >60 years old?
hypErcellular
38What are the main cell development in the BM?
"erythrocytes
megakaryocytes
granulocytes"
39What is the function of megakaryocytes?
produce platelets
40What is the function of granulocytes?
help body fight bacterial infections
41What kind of environment is in the bone marrow?
hematopoietic microenvironment
42What are the largest cell in the BM?
megakaryocytes
43Where is the erythroblastic area found?
erythroblastic island surrounding the mq
44Why do erythroblasts congregate around mq?
mq produces iron to make Hb
45Where are megakaryocytes found?
close to sinusoid bc it's a parent cell that produces platelets rupture and releases platelet to sinuses
46What happens to cells as they get far from mq in BM?
"farther away → more mature
close → less mature"
47What is the BM per body weight?
"3.4-5.9% body weight
1600-3700 g
30-50mL/KBW"
48What are the sites of hematopoiesis at birth in BM?
all bones
49What are the sites of hematopoiesis by age 7 in BM?
fat replaces red in long bones
50What are the sites of hematopoiesis by adolescence in BM?
only flat bones (skull, vertebrae, pelvic, sternum) will be haematopoietically active
51Where are the bone marrow specimen collection sites?
"Posterior iliac crest (spine of pelvis)
Anterior superior iliac crest (spine of the pelvis)
sternum"
52What kind of tests does BM aspiration use?
cytologic typing / flow cytometry
53What does aspiration of BM test for?
hematopoietic cell proportions (M:E)
54What does biopsy of BM look for?
"Cellularity (hypo / hypercellular)
certain disease state"
55What kind of examination is done on the BM?
"low power examination
high power examination (ID cells)"
56What stain is used to examine BM?
Prussian blue iron stain examination
57What does BM examination look for?
cellularity and cell density
58What is a reliable diagnostic tool for evaluating BM pathologies?
BM aspirate or imprint examination (?)
59What are the components of a BM examination report?
"pt history, CBC
cellularity, megakaryocytes, maturation, addt'l hematologic cells
stromal cells
differential count
M:E, iron stores, diagnosis"
60What cells do addt'l hematologic cells refer to In the BM exam?
eosinophils, basophils, mast cells, lymphocytes, monocytes, and histocytes
61How are stromal cells observed in the BM examination?
"# and morphology of osteoblasts, osteoclasts, trabeculae, fibroblasts, adipocytes, and endothelial cells
appearance of sinuses;
presence of amyloid, granulomas, fibrosis, necrosis"
62What is the application for iron stain in BM studies?
ID of iron deficiency, iron overload
63What is the application of cytochemical and cytogenetic studies in BM?
"diagnosis of leukemias / lymphomas
-genetic : acute leukemias via deletions, translations, polysomy; remission studies"
64What is the purpose of molecular BM studies?
PCR for diagnostic pt mutations, minimal residual disease studies
65What is the purpose of fluorescent in situ hybridization?
"staining for diagnostic mutations;
minimal residual disease studies"
66What is the purpose of flow cytometry in BM studies?
"immunophenotyping, usually of malignant hematopoietic cells, cinonality;
minimal residual disease study"
67What can the liver do, though not necessarily its main function?
major site of hematopoiesis during 2nd trimester of fetal development
68What is the structure of the liver?
"2 lobes beneath diaphragm of abdomen cavity;
optimal for gathering, xferring, and eliminating substances thru bile duct"
69What are the importance cells in the liver?
"Kupffer cells (mq)
endothelial cells"
70What do Kupffer cells do?
"remove senescent cells and foreign debris
(destroy cell debris and engulf sick RBCs)"
71What do endothelial cells do?
line the sinusoids of liver
72What are the pathophysiologic changes of the liver?
"porphyrias, hemolytic anemias,
extramedullary hematopoiesis, storage diseases
hepatitis, cirrhosis"
73What is the function of the spleen?
indiscriminate filter of circulating blood
74Where is the spleen found?
"largest lymphoid organ lies beneath diaphragm, behind the fundus of the stomach in upper L quadrant of abdomen;
surrounded by peritoneum "
75What are the main areas of the spleen?
"white pulp
red pulp
marginal zone"
76What can be found in the white pulp of spleen?
"follicles containing lymphocytes, mq, dendritic cells,
germinal centers (B cells), T cells in periarteriolar lymphatic sheath (PALS)"
77What can be found in the red pulp of spleen?
cords of Billroth, splenic mq, culling and pitting functions
78What do cords of Billroth contain?
loosely connected mq, creating a sponge-like matrix that acts as a filter; increase dmg and stress of RBCs to remove abnormal RBCs
79What is culling in red pulp of spleen?
cells are phagocytized with subsequent degradation of cell organelles
80What is pitting in red pulp of spleen?
splenic mq remove inclusions or damaged surface membrane from circulating RBCs
81What can be found in the marginal zone of spleen?
"surrounds the white pulp
memory B cells, mq, CD4+ T cells"
82What are some things that can lead to pathophysiologic changes in the spleen?
"microvascular
environment
splenomegaly"
83What happens to the spleen in splenomegaly?
spleen becomes enlarged
84What are the benefits of splenectomy?
"Hereditary spherocytosis (HS)
ITP (immune thrombocytopenic purpura)
AIHA (autoimmune hemolytic anemia)
autosplenectomy (?)"
85When would splenectomy be beneficial for HS and AIHA?
when there is excessive destruction of RBcs and corticosteroids cannot suppress hemolysis
86When would splenectomy be beneficial for ITP?
storage disorder resulting in cytopenias
87What results in autosplenectomy?
Repeated infarcts caused by sickled RBCs trapped in small-vessel circulation of spleen causing tissue dmg and necrosis
88What is the function of the lymph nodes?
Filters lymph, running in parallel with blood circulation
89What is the location and structure of lymph nodes?
bean shaped structure with outer cortex and inner medulla
90What are the pathophysiologic changes of the lymph nodes?
"adenitis
malignant tumors
lymphoma vs lymphocytic leukemia"
91What is adenitis?
infection of inflammation of lymph node
92What is the difference between lymphoma and lymphocytic leukemia?
"lymphoma - involve lymph node
lymphocytic leukemia - bone marrow / stem cell"
93What is the function of the thymus gland?
"primary lymphoid organ for cell development
produces T cells
pre T cells migrate to thymus to develop into CD4+ / CD8"
94What is the structure of the thymus?
"2 lobes further divided into lobules
located at the anterior mediastinum;
subdivided into cortex and medulla"
95What is the cellular distribution of the thymus?
"T lymphocytes
other cells"
96What are the pathophysiologic changes of the thymus?
"nondevelopment → lack of T cells
failure to thrive, infections, death in infants
adults not affected bc they developed T cells for life "
97What are the characteristic of stem cells?
"capable of self renewal
pluripotent
able to reconstitute hematopoietic system of a lethally irradiated host"
98What are the 2 kinds of stem cells?
"undifferentiated hematopoietic stem cell (HSC)
differentiated (committed) progenitor cell"
99What do HSCs differentiate into?
CMP (CFU-GEMM) or CLP
100What does CFU-GEMM stand for?
colony forming unit--granulocyte, erythrocyte, monocyte, megakaryocyte
101What are the progenitors of stem cells?
Unipotential and bipotential
102What are unipotential progenitors?
CFU-E, CFU-M, CFU-G, CFU-Eo, CFU-Baso, CFU-Meg, CFU-PreB, CFU-PreT
103What are bipotential progenitors?
CFU-GM
104Are the stem cells progenitor visibly different from one another?
not morphologically recognizable
105What are the theories of stem cell hematopoietic origin?
"monophyletic
polyphyletic"
106What is monophyletic origin theory?
one stem cell that can produce all blood cells
107What is polyphyletic origin theory?
each cell type has its own stem cell
108What is the start of monophyletic stem cell?
long term self renewing stem cell → short term → pluripotent hematopoietic stem cell
109What happens to the pluripotent hematopoietic stem cell in monophyletic theory?
"becomes common myeloid progenitor (CMP) or
common lymphoid progenitor (CLP)"
110What cells do the common myeloid progenitor make? (end goal)
neutrophils, monocytes, mq, eosinophil, basophil, mast cell, erythrocytes, platelets
111What cells do the common lymphoid progenitor make? (end goal)
B cell / T cell, plasma cell
112What are the 4 divisions of the CMP?
"granulocyte-monocyte progenitor
eosinophil basophil progenitor
megakaryocyte-erythrocyte progenitor
mast cell"
113What does the granulocyte-monocyte progenitor differentiate into?
myeloblast and monoblast
114What does the eosinophil-basophil progenitor differentiate into?
myeloblast (2)
115What does the megakaryocyte-erythrocyte progenitor differentiate into?
pronormoblast and megakaryoblast
116What can GM progenitor myeloblast diff into?
neutrophil
117What can GM progenitor monoblast diff into?
monocyte → mq
118what can EB progenitor myeloblast diff into?
eosinophil or basophil
119What does pronormoblast diff into?
erythrocyte
120What does megakaryoblast diff into?
megakaryocyte → platelets
121What are the 4 subdivisions of CMP?
"dendritic cell
Pre-B
Pre-T
natural killer cell"
122What does Pre-B diff into?
B lymphoblast → B cell → plasma cell
123What does Pre-T diff into?
T lymphoblast → T cell
124What are the functions of cytokines and growth factors?
positive and negative influence
125What cytokines are related to negative influence?
TGFB, TNF-a, interferons
126What cytokines are specific to the CMP line?
IL-3, IL-5
127What cytokines are specific to the CLP line?
IL-7
128Where can KITLG be seen?
in early stage progenitors
129What cytokines affect multiple stages?
KITLG, FTL3L, GM-CSF, Il-1, IL-3, IL6, IL-11