Hematopoietic Theroy Flashcards
Development, production and specialization of blood cells
Hematopoiesis
Where does hematopoiesis occur in adults and during fetal development?
-bone marrow
-Different areas of the body during fetal development
Hematopoiesis is divided into what three embryonic phases?
- Metablastic phase
- Hepatic phase
- Medullary phase
(EZ,AG,AB)
Mesoblastic period: Derived from….
Mesodermal tissue from fertilized embryo
19 days after fertilization
What is the site of the mesoblastic phase? 
Begins in blood islands cells of yolk sac (intravascular Hematopoiesis)
How long is the mesoblastic phase active for?
8 -12 weeks, duration of embryonic stage i.e. first trimester
The mesoblastic phase generates _________ cell lines.
And produces mainly what globin chains? 
Primitive
Epsilon and Zeta (EZ)
What are 3 embryonic hemoglobins made from the mesoblastic phase?
Gower 1, Gower 2, and Portland
- Only embryonic
What are the proportions of fetal (F) hemoglobin in newborns and adults?
Newborns —— 80%
Adults ————<1%
What is the primary site of cell production during fetal development (Extracellular hematopoiesis)?
The liver
-Other active sites in this period are spleen, Kidneys, thymus , and lymph nodes
The hepatic phase produces _____________ globin chains 
Alpha and gamma
“Fetal hemoglobin” (Hgb F) 
What phase continue last cell production until 1 to 2 weeks following birth but mostly in the second trimester?
Hepatic phase
What is M:E ratio?
Myeloid to euthyroid ratio (looked at in the marrow) 
Bone marrow cavities begin to form during ______ month of gestation (medullary hematopoiesis)
5th
At what phase does the bone marrow start to become the major active site (Through third trimester and beyond)?
Medullary (Myeloid) phase 
What globin chains are produced in the medullary phase?
Lots of alpha
Decreasing gamma
And a tiny bit of Beta 
Hemoglobin A1 is Made of? 
Alpha and beta globin chains
(Newborns- 20% and Adults-97%)
hemoglobin A2 is made of?
Alpha and Delta
(Newborns-<0.5% and adults 2.5%)
M:E ratio reaches adult level of __:__ By 20 weeks gestation
3:1
timed “on and off” working of certain genes is regulation of…
Gene expression
During which embryonic phase is the majority of cellular production occurring in the bone marrow?
Myeloid 
During which embryonic phase is the majority of hemoglobin produced, alpha and gamma? 
Hepatic
(But myeloid also) 
Where is marrow is active and which one is inactive?
Yellow is inactive
Red is active 
What is the number one and two site for marrow extraction in adults? In children?
- Iliac crest
- Sternum
- iliac crest and long bone of leg
Hematopoietic sites are __________ Compared to Children
Limited
The fat is found in bone marrow but not in ….
The blood 
When does fat cell conversion (yellow marrow) start and end?
Starts at age 4 and ends at 18 years of age
The process of replacing the active marrow by fat tissue during development, results in restrictive active marrow sites 
Retrogression
What is the structure of bone marrow? 
Spoke-like pattern of Venus sinuses and cords of hematopuretic tissue (red marrow) 
Red bone marrow Contains _______ the developing blood cell lines
All
What is the minor and major function of bone marrow?
Minor: antigen processing of cellular and humoral immunity
Major: production and proliferation of blood cells
What do megakaryocytes produce?
Platelets
- Most won’t be used but may just in case the body needs it (injury) 
The marrow micronenvironment includes supportive _________ matrix That is responsible for differentiation and proliferation of stem cell development. This includes stomal cells
Semi-fluid
Why are the stromal cells?
-endothelial cells
-macrophages
-Osteoblasts
-osteoclasts
-Reticular cells (Fibroblasts) 
Broad, flat cells that line the inner surface of the marrow, regulate the flow of particles
Endothelial cells
Large cells with flat vacuole, they secrete steroids and maintain bone integrity
Adipocyte 
Phagocytic cells that regulate Hematopoiesis by secretion of cytokines
Macrophages
Bone forming cells
Osteoblast
Bone-reabsorbing cells
Osteoclasts (Counteracts osteoblasts)
Associated with the formation of structural fibers, which support hematopoietic environment
Reticular cells (Fibroblast)
Lymphatic tissue is divided into what two areas?
- primary lymphatic tissue
- Secondary lymphatic tissue
What includes The primary lymphatic tissue?
Bone marrow for B-lymphocytes
The thymus for T-lymphocytes
And sites of active hematopoiesis in the fetus
What is included as secondary lymphatic tissue? 
lymph nodes
Spleen
GALT
These sites serves as reservoirs for already differentiated lymphocytes
Secondary lymphatic tissue
What is the primary tissue for T-lymphocytes development?
Thymus (Contains a cortex and medulla)
Cells enter the thymus with no ___________ Surface markers, but mature to T cells with specific immune differentiation
Identifiable
T-lymphocytes maturation progresses from cortex to the medulla and this is regulated by what two hormones?
Thymopoietin and thymosin
When does the thymus reach its largest size?
At puberty
Portion of the spleen that contains concentrations of WBCs (Lymphocytes and macrophages)
White pulp
Portion of the spleen that contains venous sinuses and cords of Billroth
Red pulp
This area contains the marginal zone and germinal center
Lymphatic nodules in the white pulp
This area of the spleen is rich in specialized B-lymph, macrophages, and blood vessels
 marginal zone
(Located in the lymphatic nodules of white pulp) 
Area in the spleen that houses the cell division and maturation of B-lymph and macrophages
Geminal center
(Located in lymphatic nodules of white pulp)
-Contain specialized macrophasis that create a filter system for RBC’s
- Old, damaged cells are removed, and/or inclusions on cells are removed
Red pulp of the spleen
What is the MAIN function of the spleen?
RBC Filtration
The spleen receives ______mL/min of blood.
Required to squeeze through narrow cords.
350
The spleen is a reservoir for ____% of circulating platelets.
30
Also a reservoir for lymphocytes
10-15% of peripheral B-lymph’s Found in nodules of spleen. The spleen is a place for ______ Production by B-lymph’s 
IgM
What are immature red blood cells?
Reticulocytes
What are the four functions of the spleen?
- RBC filtration
- Cell grooming or restructuring
- Reservoir for platelets and lymphocytes
- Immunity involvement
What are some symptoms of asplenia?
-increase platelets
-Increase lymphocytes
-Increase inclusions, or abnormal forms of RBCs
-Increase susceptibility to infection
Reduction of all three blood cell types
Pancytopenia
What are symptoms of splenomegaly and hypersplenism? 
-vascular congestion and portal hypertension
-Trapping of RBC’s, WBCs, and platelets (as many as 95%) 
-hyperactive bone marrow in response to pancytopenia
The liver begins a significant role in the _____ trimester 
2nd
a fixed phagocytic cell which forms the lining of the sinusoids of the liver and is involved in the breakdown of red blood cells
Kupffer cells
What are two cells that are found between the sinusoids of the 2 lobes of the liver?
Kupffer cells and epithelial cells
Remove debris from the blood, and are responsible for protein synthesis
Kupffer cells (macrophages) 
These cells are arranged carefully with spaces contained with interstitial fluid (Involved in the transfer of nutrients and waste products) 
Epithelial cells 
What are the functions of the liver?
-synthesize transport proteins
-Store essential minerals and vitamins that are used in DNA and RNA synthesis
-conjugated bilirubin from Hgb degradation
-Transports bilirubin to the small intestine for Excretion
Lymph nodes occurr in ______ and _______
Groups, chains
What are the two regions of lymph nodes?
• cortex
• Medela
This is between the medulla and cortex. Contains T cells and macrophages
Paracortex
Area on lymph nodes that…
focus of B cell proliferation (Germinal centers) 
Cortical nodules (Arranged in circles in outer cortex)
Area in lymph node…
B lymphs and plasma cells
Medullary cords (of the medulla) 
Lymph includes everything but…?
Red blood cells
What are three functions of the lymph nodes?
• role in the formation of new B lymphocytes from germinal centers
• Involved in the processing of specific immunoglobulins
• Involved in the filtration of matter, debris, and bacteria
Name two primary lymphatic tissues
Thymus and bone marrow
Clear fluid derive from blood, comprised of WBCs
Lymph
Patients with splenectomy, can have ________ RBCs
Flawed 
Hematopoiesis is generated from _______ cells
Stem
What are three characteristics of stem cells?
• capable of self renewal
• Give rise to differentiated prodigy
• Able to reconstitute The hematopoietic system
What are the two major types of stem cells?
• Non-committed or undifferentiated stem cells (monophyletic theory)
• Multi potential and committed cells (polyphyletic theory)
Undifferentiated “grandparents cell” that divides to give rise to prodigy cells committed to either my myeloid or lymphoid stem cell lineage
Undifferentiated stem cells, (HSCs) hematopoietic stem cells at the top
Multi potential stem cells that are the prodigy of myeloid stem cells; they are partially committed, but still retain some multipotancy, and will give rise to more differentiated prodigy
Colony-forming unit (CFU)
Any soluble proteins whose function is as yet unclear 
Factor
A factor that stimulates mitosis
Growth factor (GF) 
-AKA a mitogen
Regulatory proteins produced by cells that acts as intracellular messenger for many functions; Some are GFs (includes CSFs, Lymphokines, interleukins, interference, etc.) 
Cytokine
Growth factor responsible for maintenance and continued Proliferation of granulocytes & monocyte/macrophage
GM-CSF- granulocyte macrophage colony stimulating factor
Glycoprotein GF endocrine hormone; Produce by kidneys in response to degree of blood oxygenation; Major erythropoietic regulator targeting CFU-E
Erythropoietin (EPO)
Growth factor that regulates Megakaryopoiesis (Production of megakaryocytes) 
Thrombopoietin (TPO, aka mpl ligand) 
GFs that simulate proliferation and differentiation on specific cell lines;  they work in conjunction with CSFs; At least 18 identified so far
Interleukins (IL) 
What are the major hematopoetic cytokines? 
GM-CSF
EPO
TPO
IL
How is bone marrow examination done?
Aspirate, which is most common or biopsy
The weight of adult marrow is? 
1300 to 1500 grams
Marrow can undergo complete transformation within…
Hours to days
The aspirate of marrow Is added to EDTA, mix in centrifuge in a __________ Hematocrit tube. 
Wintrobe
What are the four layers of marrow aspirate? 
•fat layer (1-3%)
• plasma layer (% varies with hematocrit)
• myeloid /erythroid cellular layer (5-8%)
• RBC layer (Varies patient to patient)
For what use is marrow Preparation Staind?  what stain is used?
For cell morphology (Wright stain)
For iron content (Prussian blue stain)
When Prussian blue stain is used to determine iron content of marrow,  it is graded from ____- ____. What is the normal range? 
1+ to 4+
2+ to 4+ is normal
What does Prussian blue stain in marrow? 
Hemosiderin or ferritin
marrow preparation:
Examination of cellularity is expressed as the ratio of the Volume of ______________ to Volume of ___________ space for the patient’s age. 
Hematopoetic cells, marrow
What color is a positive Prussian blue stain? Negative? 
Blue
Yellow
What should be included with a marrow examination for comparison?
-peripheral blood cell count
-Platelet count
-reticulocyte count
Cellularity is estimated from gross ____________ Study and histological section of marrow biopsy
Quantitative
Examination of cellularity:
Irregularities of cellular distribution are first made with a low power scan of the slides and then estimated at _____ or _____X For cellular characteristics.
500, 1000
Marrow Examination of cellularity:
Differential count of how many cells completed? 
300-1000 (A higher number because it is marrow)
What is the normal M:E Ratio in adults?
1.5:1 to 3.3:1
(Old range- 2:1 to 4:1)
As normal cell matures for both RBCs and WBCs what trends are generally observed? 
-cell size decreases
-Nuclear chromatin pattern becomes denser
-Nucleoli disappear
-Amount and color of cytoplasm changes
-ratio of nucleus to cytoplasm changes (N:C ratio) 
Three signs of cytoplasmic maturation..
-deep blue color (high RNA content)
-Granules may appear
-Amount increases
Four signs of nuclear materation?
-nucleus decreases in size (Exits entirely in RBCs!)
-Chromatin becomes more condensed or clumped
-Color changes from reddish to bluish-purple
-nucleoli may decrease in number or become absent
Which globin chains are present in Hgb F?
Alpha and gamma
Where is globin chains make up adult hemoglobin? 
Alpha and beta
______________ is an endocrine hormone produced by kidneys in response to blood oxygen hypoxia
Erythropoietin 
Are macrophages or monocyte seen in blood?
Only monocytes, macrophages are never in blood! 
Colony forming factors are produced by _______ cells. 
Many
Where are developing red cells located in the bone marrow?
Adjacent to the outer surface of the vascular sinuses
Complete outer surface is the mature ones
