UNIT 2

Hematopoiesis

Lifelong process by which all blood cells are produced and destroyed by the different organs in the body

Erythropoiesis

Formation of new red blood cells by the body

Blast-forming unit - erythroid (BFU-E) and Colony-forming unit - erythroid (CFU-E)

Erythroid progenitors

Pronormoblast, Basophilic normoblast, Polychromatic normoblast, Orthochromic normoblast

Erythroid precursors

Bone marrow; red marrow

Both erythroid progenitor and precursor cells are found in the \____________, specifically in the \__________?

Reticulocytes and Erythrocytes

Which RBC stages are found in the peripheral blood?

True

T/F: BFU - E cells are differentiated from CFU - E cells by observing the size and number of colonies produced by each when cultured on a semisolid media catered for those type of cells for studies.

Blast-forming unit - erythroid (BFU-E)

Earliest committed erythroid progenitor

Blast-forming unit - erythroid (BFU-E)

Each of these cells give rise to thousands of nucleated erythroid precursor cells

1 week

How long does it take for a BFU-E cell to mature into a CFU-E cell?

Colony-forming unit - erythroid (CFU-E)

A well-differentiated erythroid progenitor cell that can form up to 64 nucleated erythroid precursors

Erythropoietin

CFU - E cells are regulated by what hormone?

Kidneys

EPO is produced by what organ in the body?

Increased

An increase in EPO secretion with have what effect on CFU - E production and differentiation?

1 week

How long does it take for a CFU-E cell to mature into a pronormoblast?

6-7 days

How long does it take for a pronormoblast to mature into a mature RBC?

18 - 21 days

On average, how long does it take for a BFU - E cell to mature into a mature RBC?

peripheral blood film; bone marrow smear

Morphologic identification of blood cells depends on a well-stained \___________ or \_______________

Modified Romanowski stain (Wright or Wright-Giemsa)

Stain used for erythrocyte staining and identification

Decreases

As an RBC matures, its cell size \_________

Bluish; reddish

As an RBC matures, its cytoplasm changes color from \_________ to \________

Pronormoblast

earliest morphologically recognizable erythrocyte precursor

Normoblastic nomenclature

Nomenclature used by the United States

Rubiblastic nomenclature

Preferred because it parallels the nomenclature used for granulocyte development

Erythroblastic nomenclature

Nomenclature used in the Europe

Pronormoblast

12-20 microns in diameter

Pronormoblast

Cytoplasm is stained dark blue, with an 8:1 N:C ratio

Pronormoblast

Currently has no hemoglobin, but is starting to accumulate materials for heme and globin synthesis.

Pronormoblast

Nucleus has fine stippled reticulum and 1-2 nucleoli.

Basophilic normoblast

10-15 microns in diameter.

Basophilic normoblast

Cytoplasm is stained deeper blue, with a 6:1 N:C ratio.

Basophilic normoblast

Chromatin starts to condense and makes a fine network with some clumping.

Basophilic normoblast

There are 0-1 nucleoli present and hemoglobin starts to form.

Polychromatic normoblast

10-12 microns in diameter.

Polychromatic normoblast

Cytoplasm is a mixture of pink and blue, with increased hemoglobin content.

Polychromatic normoblast

N:C ratio is 4:1 and has no nucleolus.

Polychromatic normoblast

Last erythrocyte stage capable of mitosis

Orthochromatic normoblast

8-10 microns in diameter.

Orthochromatic normoblast

Nucleus is pyknotic and condensed with chromatin.

Orthochromatic normoblast

Cytoplasm is salmon pink and has a 1:2 N:C ratio.

Orthochromatic normoblast

Last erythrocyte stage with a nucleus

Pyrenocyte

The enveloped extruded nucleus of an orthochromatic normoblast is called a\_________

Macrophages

They remove the extruded nucleus of an orthochromatic normoblast

Howell-Jolly bodies

Fragments of nucleus found in peripheral RBCs if an extruded nucleus if pinched off before complete envelopment

Reticulocyte

Also called a polychromatic erythrocyte

Reticulocyte

Last erythrocyte stage with a mitochondria

Supravital stain

Remnant RNA of a reticulocyte can be seen with a \___________?

Biconcave

A mature normal RBC has a \_________ shape

7-8 microns

A mature normal RBC are \_________ in size

Erythrokinetics

term describing the dynamics of RBC production and destruction

Erythron

name given to the collection of all stages of erythrocytes throughout the body

Tissue oxygenation

Single most important regulator of erythropoiesis

Hypoxia

State of having low oxygenation levels in tissue

Hypoxemia

State of having low blood oxygen levels

Negative feedback mechanism

Erythropoiesis runs on what kind of feedback mechanism?

Vitamin B12 and B9 (cyanocobalamin and folic acid)

Vitamins necessary for erythropoiesis

Iron

Main component of hemoglobin

Microcytic, hypochromic anemia

Iron deficiency can cause what kind of anemia?

Vitamin B12 (cyanocobalamin)

Vitamin essential in the making of DNA and nuclear maturation

Vitamin B9 (folic acid)

Vitamin used for the absorption of vitamin B12

Extrinsic Factor of Castle

Vitamin B12 is also called as \____________?

Intrinsic Factor

In order to absorb Vitamin B12 in the small intestine, \____________ from the gastric juices is needed

Megaloblastic anemia

Anemia caused by Vitamin B12 deficiency

Pernicious anemia

Anemia caused by the lack of Intrinsic Factor for Vitamin B12

Apoptosis

Programmed cell death

Necrosis

Death of cell due to environmental perturbations

120 days

Average RBC lifespan

Reticuloendothelial system

Old RBCs removed by macrophages located in the \_______________

Spleen

Most important organ in the removal of old RBCs

90%

Percentage of RBC destruction that occurs as extravascular hemolysis

Transferrin

Transport protein that returns free iron from the blood to the bone marrow

Amino acid pool

In extravascular hemolysis, globin is broken down and returned to the \_______________

Carbon monoxide

In extravascular hemolysis, the protoporphyrin ring is disassembled into \_____________ for expulsion

Bilirubin

In extravascular hemolysis, biliverdin is converted into \____________

Albumin

Transfer protein that carried bilirubin to the liver

bilirubin glucuronide

In extravascular hemolysis, bilirubin is conjugated to \_____________ and is excreted with bile in the intestine.

Stercobilinogen

Majority of the bilirubin glucuronide is expelled in the stool as \______________

Urobilinogen

A small amount of bilirubin glucuronide is reabsorbed into the blood circulation and is expelled in the urine as \________________

Prehepatic

An increase in unconjugated bilirubin indicates a problem in what stage of extravascular hemolysis?

Posthepatic

An increase in unconjugated bilirubin indicates a problem in what stage of extravascular hemolysis?

5-10%

Percentage of RBC destruction that occurs as intravascular hemolysis

Mechanical / fragmentation hemolysis

Intravascular hemolysis is also termed as \_______________

True

T/F: In intravascular hemolysis, RBCs break down within lumen of blood vessel, releasing hemoglobin directly into bloodstream

Haptoglobin

Transport protein responsible for picking up globin dimers caused by intravascular hemolysis

Liver

Haptoglobin carries hemoglobin components to what organ in the body?

Decrease

An increase in intravascular hemolysis occurrence has what effect on haptoglobin levels in circulation?

Hemosiderin

As haptoglobin levels diminish, free hemoglobin dimers are filtered and reabsorbed by the kidneys, and is converted to \___________?

Hemoglobinuria

Appearance of hemoglobin in the urine

5 g/day

Filtered hemoglobin reuptake by the renal tubular cells occur at what rate?

Methemoglobin

Free hemoglobin not taken by haptoglobin nor filtered by the kidney cells are converted into \___________?

Hemopexin

Transport protein responsible for taking methemoglobin

Hematopoiesis

continuous, regulated process of renewal, proliferation, differentiation, and maturation of all blood cell lines

Erythropoiesis

production of new red blood cells

Leukopoiesis

production of new white blood cells

Myelopoiesis

production of new granulocytes, such as neutrophils, basophils, and eosinophils'

Lymphopoiesis

production of new lymphocytes, such as T cells, B cells, and some dendritic cells

Megakaryopoiesis

production of megakaryocytes, which ultimately lead to production of platelets

Mesoblastic, hepatic, and medullary periods

Three stages of prenatal hematopoiesis

Mesoblastic period

This period begins as early as the 19th day after fertilization in the yolk sac of the embryo

Mesoblastic period

In this period, only erythrocytes are made (primitive erythroblasts)