CHAPTER 2 - HEMATOPOIESIS Flashcards
Formation and development of all blood cells
HEMATOPOIESIS
Encompasses the overall interactions of cellular proliferation, differentiation, morphogenesis, functional maturation, and death
HEMATOPOIESIS
Occurs predominantly in the bone marrow (3rd trimester)
HEMATOPOIESIS
TERMINOLOGIES IN BLOOD CELL MATURATION
Dyspoiesis
Erythropoiesis
Granulopoiesis (Lymphopoiesis)
– abnormal production of red blood cells
Dyspoiesis
MODES OF TRANSMISSION
Synchronous
Asynchronous
Concomitant, coordinated, and parallel development of nucleus and cytoplasm (remains constant)
Synchronous
Rate of maturation of nucleus and cytoplasm are the same
Synchronous
Abnormal development of blood cell
Asynchronous
Rate of maturation of nucleus and cytoplasm differs
Asynchronous
Eg. Mature nucleus within an agranular cytoplasm
Asynchronous
STAGES OF HEMATOPOIESIS
Intrauterine formation
Mesoblastic/megaloblastic Period
Hepatic Stage
Medullary or Myeloid Stage
Chief site: YOLK SAC
Mesoblastic/megaloblastic Period
Formation of “blood islands” – progenitor cell (mesodermal cells)
Mesoblastic/megaloblastic Period
Detected 19th to 20th day of gestation (8th to 12th week) – 1st month of fetal development
Mesoblastic/megaloblastic Period
Hemohistioblast → Primitive RBC (nucleated RBC)/”megaloblast of Ehrlich” → Mature RBC
Mesoblastic/megaloblastic Period
Embryonal Hb: Portland, Gower I, Gower II – for fetus
Mesoblastic/megaloblastic Period
Areas of leucopoiesis and megakaryopoiesis
Mesoblastic/megaloblastic Period
Formation of primitive endothelial cells and vascular system
Mesoblastic/megaloblastic Period
Carrier protein: Albumin
Mesoblastic/megaloblastic Period
Chief site: LIVER
Peak of activity: 3rd or 4th month (liver and spleen)
Hepatic stage
Spleen (?)
Thymus and Lymph nodes (?)
4th to 7th month
4th month
HbF (fetal hemoglobin) production
Hepatic Stage
Yolk sac decreases
Hepatic Stage
ADULT contains fetal hemoglobin
Hepatic Stage
Chief site: BONE MARROW (chief site at birth)
Medullary or Myeloid Stage
Peak of activity: 5th month (monocytes) – increases during the last trimester; 9th month (lymphocytes)
Medullary or Myeloid Stage
HbA (adult)
Medullary or Myeloid Stage
Chief site: yolk sac
Mesoblastic or Megaloblastic Phase
This phase starts on the 1st month of fetal life
Mesoblastic or Megaloblastic Phase
first develop within the blood island followed by leukopoiesis & megakaryopoiesis.
Primitive RBC (“megaloblast of Ehrlich”)
Embryonal hemoglobins are synthesized during this phase.
Mesoblastic or Megaloblastic Phase
Chief site: Liver
Hepatic Phase
This phase starts on the 3rd month of fetal life
Hepatic Phase
Fetal hemoglobin (HbF) is synthesized during this phase
Hepatic Phase
This starts on the 5th month of fetal life. It increases during the last trimester and remains the chief site at birth.
Myeloid / Medullary Phase
Production of adult hemoglobins (HbA) starts during this phase
Myeloid / Medullary Phase
Control center of the cell
Nucleus
Contains chromatin composed DNA and proteins
Nucleus
Contains nucleoli rich RNA
Nucleus
Contains the organelles
Cytoplasm
organelles
Golgi complex
Lysosomes
Ribosomes
Mitochondria
Endoplasmic reticulum
: contains hydrolytic enzymes that participate in phagocytosis
Lysosomes
: site of protein synthesis
Ribosomes
: generation of ATP
Mitochondria
: network of tubes for lipid and protein transport
Endoplasmic reticulum
Size: Large
IMMATURE/BLAST CELL
Size: Small
MATURE CELL
Nucleoli: Present
IMMATURE/BLAST CELL
Nucleoli: Absent
MATURE CELL
Chromatin: Fine and delicate
IMMATURE/BLAST CELL
Chromatin: Coarse and clumped
MATURE CELL
Nucleus: Round
IMMATURE/BLAST CELL
Nucleus: Round, lobulated, and segmented
MATURE CELL
Cytoplasm:
Basophilic
Rich in RNA
Acidic
IMMATURE/BLAST CELL
Cytoplasm:
Less basophilic
Less RNA
Basic
MATURE CELL
N:C Ratio: Low
MATURE CELL
CONTAINS NO GRANULES
BLAST CELLS
There are four types of granules seen using Wright’s stain:
Neutrophilic granules
Eosinophilic granules
Basophilic granules
Azurophilic granules
Neutrophilic granules =
pink to rose violet
Eosinophilic granules =
reddish orange
Basophilic granules =
dark purple to blue-black
Azurophilic granules =
sky blue
As cells become granular, non-specific granules become [?] except the [?] where there are no differential cytoplasmic granules.
less prominent and smaller
megakaryocytic series
Present in small numbers (constant) in the BM
Pluripotent Stem cell (PPSC)
Not morphologically identifiable
Pluripotent Stem cell (PPSC)
Has the ability to reproduce and differentiate
Pluripotent Stem cell (PPSC)
– forms the cell line for: lymphocytes (B/T cells) in response to cytokines/lymphokines/CSFs/growth factors
Lymphoid stem cell
– found in the BM
– leaves the BM (thymus)
CFU-BL
CFU-TL
Myeloid stem cell/CFU-GEMM – forms the cell line for: (?) in response to cytokines/lymphokines/CSFs/growth factors
granulocyte, erythrocyte, monocyte, megakaryocyte
– most on granulocyte, macrophage, erythrocyte
CFU-GM
– eosinophil
CFU-Eo
– basophil
CFU-Baso
– erythrocyte
BFU-E
– megakaryocyte
CFU-Meg
– regulate proliferation and differentiation
Growth Factors
GM-CSF
Erythrocyte, Neutrophil, Monocyte, Megakaryocyte, Eosinophil
G-CSF
Neutrophils
M-CSF/CSF-1
Monocyte, Macrophage
Erythropoietin (EPO)
Erythrocyte
Thrombopoietin (TPO)
Thrombocyte
Leukopoietin (LPO)
Leukocyte
IL-2
T cells, B cells, NK cells
IL-3
Multilineage stimulating factor
IL-4
T cells, B cells, Mast cells
IL-6
B cells, Stem cells
IL-7
T cells, Pre-B cells, early granulocytes
IL-11
Megakaryocytes
GM-CSF (cytokine)
Granulocytes, Macrophages, Fibroblasts, Endothelial cells
EPO
Red cell progenitors
- stem cell factor or steel factor
Kit Ligand (KL)
- stimulates myeloid, erythroid, and lymphoid progenitors
Kit Ligand (KL)
- primitive progenitor cells
Fit-3 Ligand (FL)
are surface proteins expressed by specific cell lines at different maturation stages
CD markers
As a cell matures, some [?] vanish and new ones appear
markers
More then [?] CD markers
200
: earliest BM cell
CD 34
: erythroid
CD 71
: myeloid
CD 33
: B-cell
CD 10
: T-cell
CD 7 / CD 5
RBC
EPO
Hypoxia
Pressure exerted by intramarrow growth of cells
WBC
Chemotaxis
(occurs in the presence of bacteria or allergy)
Chemotaxis
(decreased oxygen)
Hypoxia
PLATELET
Cytoplasmic shedding (fragmentation)
ERYTHROPOIETIN
↓ hemoglobin level in RBCs
↓ O2 in blood
↓ O2 in tissues (hypoxia)
↑ production of erythropoietin ny kidneys
Increases erythroid precursors
↓ hemoglobin level in RBCs
Accelerates rate of proliferation and maturation
↓ O2 in blood
Accelerates release from the BM to the PB
↓ O2 in tissues (hypoxia)
Ratio of granulocytes and their precursors to nucleated erythroid precursors
MYELOID : ERYTHROID RATIO
MYELOID : ERYTHROID RATIO
Normal =
4 – 3:1
are more numerous because of their short survival (1-2 days) as compared to RBCs with a 120 day life span
Granulocytes
ERYTHROID : MYELOID RATIO
1 :4 – 3
– bacterial
– viral infection
↑ neutrophil
↑ lymphocyte
Production and development of red blood cells
ERYTHROPOIESIS
Rate of RBC production directly relates to
packed red cell volume
RBCs exist and develop in the BM as
erythroblastic islands
Macrophages surrounded by
concentric rings of maturing normoblasts
Provides the developing RBCs the iron for
hemoglobin synthesis
Involved with phagocytosis of
extruded nuclei and senescent red cells
– RBCs that have lived their 120-day life span; removed by the spleen (“culling”)
Senescent cells
– removal of inclusions in RBCs by macrophages
Pitting
FACTORS AFFECTING RBC PRODUCTION
Growth factor
Estrogen
Prostaglandin
Vitamins and minerals
Proteins
stimulation
Growth factor
stops erythropoietin prod
Estrogen
help regulate EPO production and also enhances its effect on the erythroid progenitor cells
Prostaglandin
– regulation, stimulation, and stops erythropoietin prod
Prostaglandin
Vitamins and minerals
Folic acid, Vitamin b12
Co, Mn, Zn, Vit C, E, B6, Thiamine, Riboflavin, Pantothenic acid
Iron, Copper
CONSEQUENCES OF INCREASED ERYTHROPOIETIN
Reticulocytes are prematurely released
In more sever conditions, larger macroreticulocytes are seen
(stress reticulocytes)
SUBSTANCES REQUIRED:
Iron
Folic acid and Vitamin b12
– hemoglobin synthesis (helps binding to certain protein)
Iron
– normal DNA replication and division
Folic acid and Vitamin b12
: provides maximum membrane surface area
“Biconcave disc”
Facilitates movement of gases
ERYTHROCYTE MEMBRANE
The RBC is deformable as it moves through the
microvasculature
ERYTHROCYTE MEMBRANE
Composed of:
Protein – 50%
Lipid – 40%
CHO – 10%
ERYTHROCYTE MEMBRANE
External surface:
Lecithin
Glycolipid
Sphingomyelin
ERYTHROCYTE MEMBRANE
Internal surface:
Cephalin
Phosphatidyl
Inositol
P. serine
The cholesterol content depends upon:
Plasma cholesterol level (↑ RBC membrane rigidity)
Bile acids
LCAT activity (lecithin cholesterol aycl transferase)
TWO CLASSES OF PROTEINS
Integral
Peripheral
primarily glycophorin A (responsible for the negative charge of the RBC surface)
Integral
Inner and outer surface
Integral
Carry various antigens
Integral
attached to the inner ends of integral protein
Peripheral
Spectrin and Actin (create the framework)
Peripheral
Maintains biconcave shape
Peripheral
– deformability of RBC
Actin
(create the framework)
Spectrin and Actin
90% of glycolysis is anaerobic
Embden Meyerhoff Pathway
10% of glucose molecules undergo the
Aerobic Hexose Monophosphate Shunt
Allows production of reduced glutathione
Aerobic Hexose Monophosphate Shunt
Prevents oxidative denaturation of hemoglobin
Aerobic Hexose Monophosphate Shunt
Maintains iron present in hemoglobin in the reduced state (Fe++) for oxygen transport
Methemoglobin Reductase Pathway
Mainly used by the body
Methemoglobin Reductase Pathway
Chocolate brown color
Methemoglobin Reductase Pathway
Allows the production of 2,3-DPG
Rapoport Leubering Pathway
Regulates affinity of hemoglobin with oxygen
Rapoport Leubering Pathway
– progenitor cell (mesodermal cells)
“blood islands”
(chief site at birth)
BONE MARROW
(responsible for the negative charge of the RBC surface)
glycophorin A
