CHAPTER 2 - HEMATOPOIESIS Flashcards by Arriane Cyrel (MTI)

Q

Formation and development of all blood cells

A

HEMATOPOIESIS

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Encompasses the overall interactions of cellular proliferation, differentiation, morphogenesis, functional maturation, and death

A

HEMATOPOIESIS

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Occurs predominantly in the bone marrow (3rd trimester)

A

HEMATOPOIESIS

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

TERMINOLOGIES IN BLOOD CELL MATURATION

A

Dyspoiesis
Erythropoiesis
Granulopoiesis (Lymphopoiesis)

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

– abnormal production of red blood cells

A

Dyspoiesis

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

MODES OF TRANSMISSION

A

Synchronous
Asynchronous

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Concomitant, coordinated, and parallel development of nucleus and cytoplasm (remains constant)

A

Synchronous

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Rate of maturation of nucleus and cytoplasm are the same

A

Synchronous

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Abnormal development of blood cell

A

Asynchronous

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Rate of maturation of nucleus and cytoplasm differs

A

Asynchronous

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Eg. Mature nucleus within an agranular cytoplasm

A

Asynchronous

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

STAGES OF HEMATOPOIESIS
Intrauterine formation

A

Mesoblastic/megaloblastic Period
Hepatic Stage
Medullary or Myeloid Stage

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Chief site: YOLK SAC

A

Mesoblastic/megaloblastic Period

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Formation of “blood islands” – progenitor cell (mesodermal cells)

A

Mesoblastic/megaloblastic Period

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Detected 19th to 20th day of gestation (8th to 12th week) – 1st month of fetal development

A

Mesoblastic/megaloblastic Period

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Hemohistioblast → Primitive RBC (nucleated RBC)/”megaloblast of Ehrlich” → Mature RBC

A

Mesoblastic/megaloblastic Period

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Embryonal Hb: Portland, Gower I, Gower II – for fetus

A

Mesoblastic/megaloblastic Period

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Areas of leucopoiesis and megakaryopoiesis

A

Mesoblastic/megaloblastic Period

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Formation of primitive endothelial cells and vascular system

A

Mesoblastic/megaloblastic Period

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Carrier protein: Albumin

A

Mesoblastic/megaloblastic Period

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Chief site: LIVER

A

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Peak of activity: 3rd or 4th month (liver and spleen)

A

Hepatic stage

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Spleen (?)
Thymus and Lymph nodes (?)

A

4th to 7th month
4th month

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

HbF (fetal hemoglobin) production

A

Hepatic Stage

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

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