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Flashcards in L1: Hematopoiesis Deck (63)

In blood w/ and w/o anti-coagulation after centrifugation, where do clotting factors reside?

W/o anticoagulant: In the clot, which contains cells and coagulation factors

W/ anticoagulant: In plasma


In the adult peripheral blood, what are the WBCs? Which are most and least numerous?

Neutrophils > Lymphocytes > Monocytes > Eosinophiols > Basophils

"Never Let Monkeys Eat Bananas"


Do RBCs have a nucleus?



Do WBCs have a nucleus?



Do platelets have a nucleus?



What is the average blood volume in adult men and women?

Adult men: 5 to 6 liters
Adult women: 4 to 5 liters


Myeloid development

Bone marrow
Includes production of neutrophils, eosinophils, basophils, monocytes, erythrocytes, platelets


Lymphoid development

Primary sites: Bone marrow (B lymphs) and thymus (T lymphs)
Secondary sites: Spleen, lymph nodes, gut-associated tissue (where B and T cells become competent and proliferate in response to antigen)


Describe site of hematopoiesis by age

In fetus, liver produces hematopoetic cells. Bone marrow begins to produce blood cells in second trimester and is the major organ producing blood at birth. The liver stops producing hematopoietic cells shortly after birth.


Why do newborns have a "pot belly" appearance?

They have a slightly enlarged liver due to residual hematopoiesis


What are the functions of bone marrow?

Constitutive hematopoiesis: provides a continuous and adequate supply of blood and immune cells throughout life ("steady state")

Induced hematopoiesis: Response abnormal conditions (e.g. increased production of neutrophils in response to bacterial infections)

Apoptosis: programmed cell death of old, damaged cells, or cells no longer needed


What are the components of bone marrow?

Hematopoietic cells

Support (stromal) cells and extracellular matrix: adipocytes endothelial cells, macrophages and lymphocytes, reticular adventitial cells (fibroblasts), collagen, proteoglycans, fibronectin, etc.

Bone-producing cells: ostebolasts and osteoclasts

Blood vessels: arteries, veins, and a network of sinuses


Where do blood cells develop in the bone marrow?

They develop in cords, suspended b/w trabeculae ("scaffold" of bone)


What separates the network of blood sinuses from the blood cells?

A lining of endothelial cells, which forms a "barrier" b/w them


What cells make platelets?



What is a hematopoietic microenvironment?

Environment that is specific for every type of cell that develops in the bone marrow

Each niche has specialized support cells to nurture and protect a particular type of cell


What are cell location, trafficking and growth in hematopoietic microenvironments regulated by?

Cytokine and chemokine secretion (produced by stromal cells)

Receptors and adhesion molecules on cells


How are mature blood cells released?

As blood cells mature, they change their receptors and adhesion molecules and move closer to the edge.

They migrate through the endothelial cells into the vascular sinus, then into the peripheral blood.


How are platelets released?

Megakaryocytes (located next to the sinus) protrude proplatelet processes through endothelial cells and release platelets directly into the sinus


When are blood cells normally released into the sinus?

When they are almost fully mature


What is blood cell release controlled by?

Adhesion molecules and cytokines


What does red marrow consist of?

90% hematopoietic cells


What does yellow marrow consist of?

Adipocytes and some blood cells


In infants, what do bones consist of?

90 - 100% red marrow in all bones


What is involution?

Process by which with age (beginning at 5 - 7 years), fat begins to replace some of the red marrow


At about 20 years of age, where is red marrow located?

Only located in axial skeleton, a little bit in skull, pelvis (flat bones), and proximal ends of long bones


Why is bone marrow collected from the iliac crest?

Bc the pelvic area still contains red marrow, which is hematopoietic tissue


What is medullary hematopoiesis?

Blood cell growth in bone marrow cavity


What is extramedullary hematopoiesis?

Blood cell growth outside the bone marrow cavity, commonly in the spleen and liver

Occurs in abnormal conditions in adults


How is the body's response to increase in demand for cells regulated?

Regulated by growth factors


How does the body respond to increase in demand for cells?

Increase in proportion of hematopoietic cells to fat in bone marrow (increased cellularity)

Early release of cells from bone marrow (will see immature cells in peripheral blood smears)

Extramedullary hematopoiesis - blood cells will develop in spleen and liver (see hepatosplenomegaly on physical exam)


Why do bone deformities sometimes occur in children when the proportion of hemtatpoietic cells to fat in bone marrow is increased?

Fat can be totally replaced by hematopoietic tissue to the point that bones can actually expand and cause bone deformities

Such as in untreated thalassemia major


What are the hematopoietic cell compartments in bone marrow?

<0.1% hematopoietic stem cells (HSCs): a low, fixed # of HSCs remain in the bone marrow throughout life; are capable of self-renewal

About 3% progenitor cells (PCs): committed to certain blood cell types (lineages); not capable of self-renewal

>95% maturing cells: morphologically identifiable cells that are committed to be a certain lineage


Describe basic blood differentiation from HSC

HSC → common myeloid progenitor (CMP) and common lymphoid progenitor (CLP)

CMP →megakaryocyte (→ platelet), erythrocyte, neutrophil, eosinophil, basophil, monocyte (→macrophage)

CLP → T lymph, B lymph (→plasma cell), NK cell


How does a limited # number of HSCs provide blood and immune cells over a lifetime?

HSCs are capable of self-renewal through asymmetric division

When it divides, it produces one cell that differentiates and one cell that retains stem cell properties


What does the pluripotency of HSCs mean?

It can differentiate into all blood cell types

One HSC can repopulate all the blood and immune cells in the body


Describe myelopoiesis

Bone marrow:
Myeloblast → promyelocyte → myelocytes → metamyelocyte

Peripheral blood:
→ band → segmented neutrophil


In myelopoiesis, what distinguishes a band from a metamyelocyte?

The nucleus shape (semi-circle shape in a band)


Describe lymphopoiesis

Bone marrow:
Lymphoblast → prolymphocyte

Peripheral blood:
→ Lymphocyte


Describe monopoiesis

Bone marrow: Monoblast → promonocyte

Peripheral blood:
→ Monocyte


Describe megakaryopoiesis

Bone marrow: Megakaryoblast → promegakaryocyte → megakaryocyte

Peripheral blood:
→ platelets


Describe erythropoesis

Bone marrow: Immature RBC precursor cells → nucleated RBCs or NRBCs

Peripheral blood:
→ reticulocyte → erythrocyte

The nucleus is extruded as cell is being released through the endothelial cells into the peripheral blood


What are the neutrophil pools?

50% MNP (storage) and 50% CNP (functional)

MNP = marginal neutrophil pool; neturophils localized to capillary walls mainly in lung, spleen, liver

CNP = circulating neutrophil pool


What is the life span of neutrophils in peripheral blood?

They circulate for about 10 - 14 hours before they go into tissues


What are the first responders microorganisms?



How can the body rapidly increase circulating neutrophils?

Mobilize them from MNP to CNP

Provides rapid increase in WBCs to fight off infection

Steroids can also increase neutrophils due to MNP → CNP


Why are neutrophils the first blood cells to decrease w/ chemotherapy?

Bc they have the shortest lifespan in circulation


What is the life span of red blood cells in peripheral blood?

120 days

100% of RBCs are circulating


Why is HbA1c level used to monitor diabetes mellitus?

It reflects the glycation of hemoglobin (addition of glucose) as the RBC ages


What is the life span of platelets in peripheral blood?

7 - 10 days

30% of platelets are stored in spleen and 70% are circulating/functional


What does aspirin do to platelets?

Irreversibly binds to cyclooxygenase in the plateley and inhibits its activation for the remainder of its life span

After aspirin is discontinued, it takes about a week for new platelets to replace the inhibited platelets to restore platelet activity


What does deficiency of vitamin B12 or folate result in?

Impaired DNA synthesis in the nucleus → ineffective hematopoiesis (apoptosis of hematopoietic cells) → megaloblastic anemia

Bone marrow:
Nuclear-cytoplasmic asynchrony (nucleus matures slower than the cytoplasm) and large, abnormal RBC precursors

Peripheral blood:
Pancytopenia (decreased WBCs, RBCs, and PLTs), oval macrocytes, hypersegmented neutrophils


Where are growth factors/cytokines produced?

Most produced in the bone marrow microenvironment

Exception is erythropoietin (EPO) which is secreted by the kidney via endocrine signaling


What do growth factors/cytokines do?

Bind to growth factor receptors on hematopoietic cells


What is erythropoietin (EPO) released by and in response to what?

By kidney (peritubular cells) in response to hypoxia caused by anemia, repiratory disorders, high altitude


What does release of EPO cause?

It binds to receptor on RBC progenitors in bone marrow and triggers them to increase or speed up production of RBCs

It causes increased RBCs in circulation and some immature RBCs are released (reticulocytes, NRBCs)


What prevents more erythropoietin production by peritubular cells of kidney?

Negative feedback by increased RBCs in circulation and release of immature RBCs


What is used to treat anemia in pts with chronic kidney disease?

Exogenous EPO


What are the colony stimulating factors? What are their functions?

G-CSF (granulocyte colony-stimulating factor): stimulates differentiation and maturation of neutrophils; mobilizes HSCs into the peripheral blood

GM-CSF (granulocyte-macrophage colony-stimulating factor): stimulates differentiatoin and maturation of neutrophils and monocytes; mobilizes HSCs into the peripheral blood


What is exogenous G-CSF used for?

To increase the WBC count in cancer pt w/ leukopenia (low WBC count) by mobilizing WBCs from the BM to PB

Also given to donors to mobilize their HSCs and progenitor cells into the PB. After mobilization, these cells are collected by venous access and leukapheresis, and are used for treatment in patients w/ various hematologic conditions. This eliminates the need for bone marrow aspiration.


What is the preferred site of bone marrow collection?

Posterior iliac crest (location w/ hematopoietic marrow)


Describe aspirate method for bone marrow collection. What is it used for?

Suctioned w/ syringe; contains marrow particles and sinusoidal blood

Used to identify abnormal morphology of hematopoietic cells


Describe biopsy method for bone marrow collection. What is it used for?

"Core" of bone marrow obtained using a biopsy needle

Important to observe bone marrow architecture and cells in fixed location; helpful for diagnosis of benign and malignant conditions