Hematopoiesis Flashcards
• Continuous, regulated process of renewal, proliferation, differentiation and maturation of ALL BLOOD CELLS LINES
HEMATOPOIESIS
HEMATOPOIESIS
Continuous, regulated process of renewal, proliferation, differentiation and maturation of ALL BLOOD CELLS LINES
• Capable of self-renewal and directed differentiation into all required cell lineages
HEMATOPOIETIC STEM CELL
HEMATOPOIETIC DEVELOPMENT
Yolk Sac & Mesoblastic Phase
Hepatic Phase
Medullary (Myeloid) Phase
Developing Human (FETAL DEVELOPMENT)
• Hematopoiesis can be characterized as a select distribution of embryonic cells in specific sites:
• Yolk sac
• Aorta-gonad-mesonephros region (AGM)
• Fetal liver
• Bone Marrow
RESTRICTED to the BONE MARROW
Healthy Adult
YOLK SAC & MESOBLASTIC PHASE
• Hematopoiesis begin around______ of embryonic development after fertilization
19th day
YOLK SAC & MESOBLASTIC PHASE
Cells from the MESODERM migrate to the______
cells form_______ = IMPORTANT IN EARLY EMBRYOGENESIS
• Produce HEMOGLOBIN…
YOLK SAC
PRIMITIVE ERYTHROBLAST
(Gower 1, Gower 2 & Portland)
contains either DEFINITIVE HSC or CELLS that can give rise to HSC
YOLK SAC
Cells from the______ origin migrate to the_____ and give rise to the HSCs for definitive or permanent adult hematopoiesis.
MESODERM
AGM region
• Cellular formation, proliferation, differentiation, maturation of BC
Hematopoiesis
___________
• Primary sites: blood islands of YOLK SAC of human embryo (______day of gestation)
MESOBLASTIC STAGE
19th day
Blood islands remain active:
8-12 weeks
In Mesoblastic stage,
• Blood cell formed:__________ (1st blood cell formed by 1st month of embryonic life)
ERYTHROBLAST
Mesoblastic stage
• EMBRYONIC HEMOGLOBIN
PoZeGa, GoZE, GAE
• Gower I: 2z Ze
• Portland: 2z 2g
• Gower Il: 2a 2e
HEPATIC STAGE
• Primary sites:
FETAL LIVER
Hepatic stage
• Blood cell formed:
•: still produced
•: 3rd month of gestation
•: 4th mon
•: 5th mon
ERYTHROCTES
GRANULOCYTE and MEGAKARYOCTE
LYMPHOCYTE
MONOCYTE
Hepatic Stage
• Mid-fetal life:______ and______ limited role as 2ndary lymphoid organs
• Remain active in producing lymphocytes throughout life
SPLEEN and Lymph Nodes
Hepatic Stage
•: 4th mon of gestation
•
FETAL HEMOGLOBIN
Hb F: 2a 2g
MYELOID STAGE
• Primary sites:
BONE MARROW
• Hematopoiesis in liver begins to dec. by the last trimester
MYELOID STAGE
MYELOID STAGE
• ADULT HEMOGLOBIN
• Hb A1: 2a 2b
• Hb A2: 2a 2d
EMBRYONIC HEMOGLOBIN
Mesoblastic stage
FETAL HEMOGLOBIN
Hepatic stage
ADULT HEMOGLOBIN
Myeloid stage
POST-NATAL HEMATOPOIESIS
• At BIRTH:_______ (only site for production of lymphocytes
BM
Post Natal
• At BIRTH: BM (only site for pro lymphocytes
• FLAT BONES:
• Sternum
• Ribs
• Vertebrae
• Skull
• Pelvis
Post natal
• In ADULT:
•________
• BMA: Iliac crest (PSIS), CSF (L3-L4 or L4-L5)
Sternum, flat bones
STEM CELLS
• PLURIpotent or MULTIpotent
• Retain ability to differentiate into ANY CELL LINE
• CFU-Spleen
• PLURIpotent or MULTIpotent
• Retain ability to differentiate into ANY CELL LINE
• CFU-Spleen
SC
• BFU-E, CFU-E, CFU-MEG, CFU-GM
PROGENITOR (COMMITED cells)
• Differentiate into ONE cell line
PROGENITOR (COMMITED cells)
• UNIpotential
PROGENITOR (COMMITED cells)
• BLAST form
• Myeloblast, Megakaryoblast, Erythroblast
• PRECURSOR CELLS
HEMATOPOIETIC DEVELOPMENT
Hematopoiesis can be characterized as a select distribution of embryonic cells in specific sites:
• Yolk sac
• Aorta-gonad-mesonephros region (AGM)
• Fetal liver
• Bone Marrow
Hematopoiesis in Healthy Adult
RESTRICTED to the_____
BONE MARROW
PHASES OF HEMATOPOIETIC DEVELOPMENT
• Yolk sac — YOLK SAC PHASE
• Aorta-gonad-mesonephros region (AGM) — MESOBLASTIC PHASE
• Fetal liver — HEPATIC PHASE
• Bone Marrow — MEDULLARY PHASE
YOLK SAC & MESOBLASTIC PHASE
• Hematopoiesis begin around______ of embryonic development after fertilization
19th day
YOLK SAC & MESOBLASTIC PHASE
Cells from the_____ migrate to the____
cells form ________= IMPORTANT IN EARLY EMBRYOGENESIS
MESODERM
YOLK SAC
PRIMITIVE ERYTHROBLAST
PRIMITIVE ERYTHROBLAST = IMPORTANT IN EARLY EMBRYOGENESIS
• Produce HEMOGLOBIN…
Gower 1, Gower 2 & Portland
Contains either DEFINITIVE HSC or CELLS that can give rise to HSC
YOLK SAC
YOLK SAC & MESOBLASTIC PHASE
Cells from the MESODERM origin migrate to the______ and give rise to the______ for definitive or permanent adult hematopoiesis.
AGM region
HSCs
HEPATIC PHASE
• Hematopoiesis begins at____
5 to 7 gestational weeks
HEPATIC PHASE
Extravascular or Intravascular
• EXTRAVASCULAR
Major site in hepatic phase
Liver
HEPATIC PHASE
• LIVER: major site
• Peak:
• Declines:
3rd month
after 6th month (why? Cuz sa bone marrow na major siye after 6 months)
•Characterized by recognizable clusters of DEVELOPING ERYTHROBLAST, GRANULOCYTES & MONOCYTES
HEPATIC PHASE
HEPATIC PHASE
•Characterized by recognizable clusters of (3)
DEVELOPING ERYTHROBLAST
GRANULOCYTES
MONOCYTES
Sites during Hepatic Phase
SITES:
fetal liver
thymus
spleen
placenta
bone
marrow
• LYMPHOID CELLS begin to appear during this stage
Hepatic phase
This phase signal the BEGINNING of definitive hematopoiesis
Hepatic phase
• DECLINE in primitive hematopoiesis of yolk sac
Hepatic phase
HEPATIC PHASE
•1ST fully developed organ in the fetus
THYMUS
• Major site of T cell production
Thymus
HEPATIC PHASE
Organ that produces B cells
KINDEY & SPLEEN
During the hepatic phase
•_______ gradually decreases granulocytic production
• Contributes solely to______
Spleen
lymphoiesis
In this phase
• Productions of Megakaryocytes begins
Hepatic phase
HEMOGLOBIN PRODUCED IN HEPATIC PHASE
• Fetal Hemoglobin (Hb F) : Predominant Hb
• Adult Hemoglobin (Hb A) : Detectable levels
• Hb B
Hepatic phase
• Fetal Hemoglobin (Hb F) :
• Adult Hemoglobin (Hb A) :
• (Hb B)
• Fetal Hemoglobin (Hb F) : a & g
• Adult Hemoglobin (Hb A) : a & B
• (Hb B) : a & d
MEDULLARY (MYELOID) PHASE
• Hematopoiesis in the
BONE MARROW
It occurs in the medulla or inner part of bone marrow cavity
BEGINS: ______fetal development
Medullary phase
4th and 5th month
•______ of gestation: BM is the PRIMARY SITE OF HEMATOPOIESIS
24 weeks
• 24 weeks of gestation:_____ is the PRIMARY SITE OF HEMATOPOIESIS
BM
HSC and Mesenchymal Cells migrate into the core of the bone
MEDULLARY (MYELOID) PHASE
Red bone
• Myeloid activity: apparent during this stage
Medullary phase
Medullary phase
Myeloid-to-erythroid ratio:
3:1 to 4:1
MEDULLARY PHASE
DETECTABLE DURING THIS PHASE:
Erythropoietin(EPO)
granulocyte colony-stimulating factor (G-CSF)
granulocyte-macrophage colony stimulating factor(GM-CSF)
HB F
ADULT HEMATOPOIETIC TISSUE
• Location:
BONE MARROW
LYMPH NODES
SPLEEN
LIVER
THYMUS
• Contains developing erythroid, myeloid, megakaryocytic, and lymphoid cells
BONE MARROW
Lymphoid development
• Primary lymphoid tissue:
• Secondary lymphoid tissue:
bone marrow & thymus
spleen, lymph nodes, and mucosa-associated lymphoid tissue
• One of the largest organs in the body
BONE MARROW
BONE MARROW
• 2 COMPONENTS:
RED MARROW & YELLOW MARROW
RED MARROW & YELLOW MARROW
• Infancy and early childhood: Abundant______
• 5 to 7 years of age:_____ more Abundant
Red Marrow
Adipocytes
T or F
MARROW CELLULARITY: decreases with age
True
Sites of Red Marrow:
• sternum, vertebrae, scapulae, pelvis, ribs, skull, and proximal portion of the long bones
BONE MARROW includes
Stromal cells
Endothelial cells
Adipocytes
• Stromal cells:
• Endothelial cells.adipocytes, macrophages and lymphocytes, osteoclasts and reticular adventitial cells.
• Regulate the flow of particles entering and leaving hematopoietic spaces in the vascular sinuses
• Endothelial cells
• Regulating the volume of the marrow in w/c active Hematopoiesis occurs
• Secrete cytokines or growth factors
Adipocytes
•2 lobes situated beneath the diaphragm in the abdominal cavity.
• Major site of blood production (2nd trimester)
LIVER
LIVER
Adults:
Functions:
Protein synthesis, degradation, coagulation factor synthesis, carbohydrate and lipid metabolism, drug and toxin clearance, iron recycling and storage, and hemoglobin deradation
LIVER
Gathering, transferring and eliminating substances through the…
bile duct
• Macrophage that remove senescent cells and foreign debris from the blood that circulates through the liver
• Secretes mediators
KUPFFER CELLS
• Largest lymphoid organ in the body
SPLEEN
Spleen
• Contains______ of blood
• Storage site for_____
350mL
platelets
FUNCTION: indiscriminate filter of the circulating blood
Spleen
3 TYPES OF SPLENIC TISSUE:
• White pulp
• Marginal zone
• Red pulp
- reticular meshwork
Marginal zone
- cords of reticular cell meshwork
(cords of billroth) = sponge-like matrix
Remove senescent or abnormal RBCs
• Red pulp
Spleen
Remove senescent or abnormal RBCs
• 2 methods:
CULLING
PITTING
• Organs of the lymphatic system located along the lymphatic capillaries that are prallel to, but not part of circulatory system
LYMPH NODES
• BEAN SHAPED structure (1-5 mm in dm)
Lymph nodes
• Present in groups or chains at various intervals along lymphatic vessels
Lymph node
• LIQUID PORTIONS of blood that escapes into the connective tissue
• Characterized by a low protein concentration and the absence of RBCs
• Filtered by lymph nodes
LYMPH
LYMPH NODES
• FUNCTIONS:
• Site of lymphocyte proliferation
• Initiation of the specific immune response to foreign antigen
• Filter particulate matter, debris and bacteria
• 1st - originates from endodermal and mesenchymal tissue
• 2nd - populated initially by primitive lymphoid cells from the yolk sac and the liver
THYMUS
• Consist 2 lobes (0.5 to 2 cm in dm) divided into lobules
Thymus
• Location: upper part of the anterior madiastinum, level of the great vessels of the heart
Thymus
AREAS: (peripheral zone)& (central zone)
Cortex
Medulla
• T cells progenitors migrate to the thymus from the bone marrow for further maturation
• T cell dependent area: spleen,lymph nodes other lyphoid organs
Lymphoid tissue
THYMUS
•: is an efficient, well-developed organ
• Size of the thymus is related to____
BIRTH
age
• weight at birth: 12-15g increases to 30-40g (puberty)
Decreases to _____ater ages
10-15g