18.3 Formed Elements in the Blood

Eryhtrocytes

Size(Diameter): 7.5 um

Function: Transport oxygen and carbon dioxide

Life Span: 120 days

Density(Average number per mm3 of blood= uL): In genetic females, 4.8 million, in genetic males, 5.4 millions

Leukocytes(neutrophils, esoinophils, basophils, monocytes, and lymphocytes)

Size(Diameter): 1.5 to 3 times larger than an erythrocyte; 11.25-22.5 um

Function: Intimate immune response; defend against potentially harmful substances

Life Span: varies from 12 hours (neutrophils) to years (lymphocytes)

Density(Average number per mm3 of blood= uL): 4500-11000

Platelets

Size(Diameter): ¼ the size of an erythrocyte; 2 um

Function: participate in hemostatsis

Life Span: 8-10 days

Density(Average number per mm3 of blood= uL):150000-400000

Hematopoiesis

the production of blood’s formed elements

Hematopoiesis begins in the

embryonic period of development, when the yolk sac forms blood stem cells and primitive formed elements.

By the 5th week of development, the

liver becomes the primary site for hematopoiesis, and continues this process until the 5th month of development, when hematopoiesis begins in red bone marrow.

Once the child is born, ___ is the main site of hematopoiesis

red bone marrow

The process of hematopoiesis starts with

hematopoietic stem cells called hemocytoblasts

Hemocytoblasts are considered

multipotient cells, meaning they can differentiate and develop into many different kinds of cells.

Hemocytoblasts product 2 different cell lines

• myeloid line

• lymphoid line

myeloid line

• forms erythrocytes

• all leukocytes except lymphocytes

• megakaryocytic(cells that produce platelets)

• mast cells

• dendritic cells(and mast cells are immune cells that migrate out of the blood and into body tissues)

Lymphoid line

forms only lymphocytes

The maturation and division of hematopoietic stem cells are influenced by

regulatory molecules that stimulate these processes called

colony-stimulating factors (CSFs) or colony-forming units (CFUs)

Colony-stimulating factors (CSFs)

are all growth factors (substances that promote cellular growth and differentiation) execept erythropoietin, which is a hormone

Substances that influence hematopoiesis (aka CSFs)

• Multi-colony-stimulating factor (multi CSF)

• Granulocyte macrophage colony stimulating factor (GM-CSF)

• Granulocyte colony stimulating factor (G-CSF)

• Macrophage colony-stimulating factor (M-CSF)

• Thrombopoietin

• Erythropoietin

Multi-colony-stimulating factor (multi CSF)

Growth Factor or Hormone?: Growth factor

Function?: Increases the formation of erythrocytes, granulocytes, monocytes, and platelets from myeloid stem cells.

Granulocyte-macrophage colony stimulating factor (GM-CSF)

Growth Factor or Hormone?: Growth factor

Function?: Accelerates the formation of all granulocytes and monocytes (which become macrophages) from their progenitor cells.

Granulocyte colony stimulating factor (G-CSF)

Growth Factor or Hormone?: Growth factor

Function?:Stimulates the formation of granulocytes from myeloblast cells.

Macrophage colony-stimulating factor (M-CSF)

Growth Factor or Hormone?: Growth factor

Function?: stimulates the production of monocytes from monoblasts

Thrombopoietin

Growth Factor or Hormone?: Growth factor

Function?: stimulates both the production of megakaryocytes in the red bone marrow and the subsequent formation of platelets

Erythropoietin (EPO)

Growth Factor or Hormone?: Hormone(produced primarily by the kidneys)

Function?: Increases the rate of production and maturation of erythrocyte progenitor and erythroblast cells.

Erythrocytes make up more than__ of formed elements, with a concentration between and _ million per cubic milimeters.

99%

4.2

6.2

Erythropoiesis

process of erythrocytes production.

Erythocytes are produced at the rate of ___ per second

3 million

Erythropoietin controls the rate of erythropoiesis by

increasing the rate of erythrocyte formation.

Nutritional requirements for erythropoiesis

• iron

• B vitamins (folic acid, riboflavin, cobalamin)

• amino acids (to build proteins, including hemoglobin)

The process of erythropoiesis begins with a

myeloid stem cell

The myeloid stem cell that begins erythropoiesis is then under the influence of

multi-CSF to form a progenitor cell.

The progenitor cell in the process of erythropoiesis then

forms a proerythroblast, which is a large, nucleated cell.

The proerythroblast in the process of erythropoiesis then

becomes an erythroblast, which is a slightly smaller cell that has ribosomes producing hemoglobin protein in its cytosol,

The next stage after proerythroblast in the process of erythropoiesis

Normoblast, a still smaller cell with more hemoglobin in the cytosol; its nucleus has been ejected.

The next stage after normoblast in the process of erythropoiesis

A cell called a reticulocyte eventually is formed.

has lost all cellular organelles except some ribosomes, so it can continue for a short time to produce hemoglobin through protein synthesis.

Transformation from myeloid still cell to reticulocytes takes

about 5 days.

Most reticulocytes in erythropoiesis complete their maturation within

the red bone marrow or while circulating in blood vessels.

The percentage of reticulocytes that mature in the circulating blood in blood vessels

about 0.5-2.0% of the circulating blood.

1 to 2 days after entering the circulation,

the ribosomes in the reticulocyte degenerate, and the reticulocyte becomes a mature erythrocyte.

Without a nucleus and cellular organelles, the mature erythrocyte is essentially a plasma membrane “bag” containing hemoglobin.

Leukocytes make up then ___ of formed elements, with a concentration between __ and -__ per cubic millimeter.

0.01%

4500 & 11000

Leukopoiesis

Production of leukocytes

3 different types of maturation processes:

• granulocyte maturation

• monocyte maturation

• lymphocyte maturation

All 3 types of granulocytes (neutrophils, basophils, and eosinophils) are derived from

a myeloid stem cell, which is stimulated by multi-CSF & GM-CSF to from a progenitor cell.

The granulocyte line develops when the ___ forms a myeloblast under the influence of G-CSF.

progenitor cell.

The myeloblast ultimately differentiates into one of 3 types of granulocytes.

Monocytes are also derived from a ___ stem cell.

myeloid.

it then differentiates into a progenitor cell, and under the influence of M-CSF this cell forms a monoblast. This is the monocyte line.

The monoblast forms a promonocyte that differntiates and matures into a

monocyte.

Lymphocytes are derived from a ___ through the lymphoid line.

lymphoid stem cell.

The lymphoid stem cells differentiates into

• B-lymphoblasts

• T-lymphoblasts.

B-lymphoblasts mature into

B-lymphocytes

T-lymphoblasts mature into

T-lymphocytes.

Some lymphoid stem cells differentiates directly into

NK (Natural killer) cells.

Platelets or thrombocytes make up less than ___ of formed elements with a concentration between ___ and ___ per cubic millimeter.

1%

150,000 & 400,000

Thrombopoiesis

The production of platelets

From the myeloid stem cell, a committed cell called ___ is produced.

Megakaryoblast

Megakaryoblast matures under the influence of thrombopoietin to form a

megakaryocyte.

Megakaryocytes are easily distinguished both by

• their large size, 100 micrometers in diameter

• their dense, multi lobed nucleus.

Thousands of platelets are formed from each

megakaryocycte.

Long extensions from the megakaryocytes will form

proplatelets.

Proplatelets will then extend through the blood vessel wall (between the endothelial cells) in the

red bone marrow.

The force from the blood flow slices these pro platelets into the fragments we know as platelets.

Megakaryocytes remain within the red bone marrow, whereas the cellular fragments that become platelets

enter the blood.

Erythrocytes

• very small flexible cells

• diameter of approximately 7.5 microns.

• referred as a formed element.

• has a unique biconcave disc structure (narrowest point is about 0.75 microns, widest point is 2.6 microns.)

• composed of a plasma membrane, it encloses about 280 million hemoglobin molecules..

Erythrocytes transport

oxygen and carbon dioxide between the tissues and lungs.

the fact that erythrocytes lack a nucleus and organelles enables them to transport respiratory gases more efficiently.

A latticework of spectrin protein supports the

• plasma membrane of the erythrocyte on its internal surface

• provides flexibility to the erythrocyte as it moves through the capillaries.

Hemoglobin

• red-pigmented protein

• transports oxygen and carbon dioxide

• each consists of 4 protein molecules called globins

• 2 of these globins are alpha chains

• 2 of these globals are beta chains

• all globin chains contain heme group

• heme group, composed of a porphyrin (organic compound) ring, with an iron ion (FE2+) in its center

• oxygen binds to the Fe2+ in heme groups for transport in the blood.

• has 4 fe2+ and is capable of binding 4 molecules of oxygen.

The oxygen binding in hemoglobin is fairly weak allowing

rapid attachment of oxygen with hemoglobin when erythrocytes pass through the blood capillaries of the lungs, and rapid detachment when erythrocytes pass through the systemic capillaries of body tissues.

Carbon dioxide and the globin molecules have a weak attachment relationship allowing

carbon dioxide to bind to the globin protein molecules as blood moves through systemic capillaries and released as blood moves through the capillaries of the lungs.

Steps in the Regulation of Erythropoiesis by EPO

1. Stimulus. The initial stimulus for EPO release is a decrease in blood oxygen levels. This decrease may be caused by the continuous removal of aged erythrocytes, blood loss, or exposure to high altitudes (where atmospheric oxygen levels are lower).

2. Receptors. Chemoreceptors within the kidneys detect low blood oxygen levels as the blood is transported through blood vessels within the kidneys.

3. Control Center. Certain cells in the kidneys release the hormone EPO into the blood. EPO is transported through the blood and reaches the red bone
   marrow.

4. Effector. Erythropoietin stimulates myeloid cells in the red bone marrow to increase the rate of erythrocyte production.

5. Net Effect. Additional erythrocytes are released into circulation (a process that takes a few days), so more oxygen can be transported from the lungs and delivered to the cells. Blood oxygen levels increase as a result.

6. Negative Feedback. Increased blood oxygen levels inhibit release of EPO from kidney cells through negative feedback. Thus, less EPO is released into the blood.

The absence of both a nucleus and cellular organelles comes at a cost to the erythrocyte and affects its

longevity.

A mature erythrocyte cannot synthesize proteins either to repair itself or to replace damaged membrane regions.

Every day about __ of the oldest circulating erythrocytes are removed from the blood

1%

These aging or damaged erythrocytes are phagocytized in both the spleen and liver by

macrophages.

3 molecular components that must be accounted for in the destruction of hemoglobin

• globin protein

• iron ion

• heme group.

Both the globin protein and iron ion are processed for recycling and reused by the body.

Heme is metabolically altered and then excreted from the body.

Steps for the breakdown of hemoglobin

• Liver and Spleen: Following phagocytosis of an erythrocyte by macrophages within the liver and spleen, hemoglobin molecules are removed from the erythrocyte and each hemoglobin is processed as follows within the macrophage: Heme with iron still attached is removed from the globin protein. The globin protein is broken down into free amino acids, which are released and the body can use to form new proteins. The iron (Fe2t) is removed from the heme and released into the blood. Its transport and storage is described shortly. The heme group (minus the Fe2t) released from hemoglobin is converted first into a green pigment called biliverdin (bil-i-ver'din; bilis = bile, verd = green). Biliverdin is eventually converted into ayellowish pigment called bilirubin (bil-i-ru'bin; rubin = reddish). Bilurubin isreleased from the macrophage. (The bilirubin at this stage is more specifically unconjugated bilirubin, which is not water-soluble and is toxic to the body, especially to brain.)

• Blood: Unconjugated bilirubin is then released into the blood, where it binds with albumin (a plasma protein) and is transported by albumin to the liver.(Albumin is required for blood transport of unconjugated bilirubin because this form of bilirubin is not water-soluble;

• Liver: Unconjugated bilirubin is removed from the blood by the liver, where it is then converted to conjugated bilirubin (the nontoxic, water-soluble form of bilirubin). This is a significant step in the processing of heme.

• Liver: Bilirubin is then eliminated from the liver into the small intestine as a component of bile, a secretion that facilitates digestion (see L section 26.3).

• Small intestine: Bilirubin is converted within the small intestine to urobilinogen (yur-ö-bi-lin'Õ-jen, ouron = urine) within the small intestine.
  Urobilinogen has two possible fates.ба

• *6a)Small and Large Intestine: Urobilinogen can continue through the small intestine and into the large intestine (primarily; about 80%) and eventually intestinal bacteria (the gut microbiome) convert urobilinogen to stercobilin, a brown pigment that is expelled from the body as a component of feces.

• 6b) Blood and Kidneys: Urobilinogen can be absorbed back into the blood (smaller quantity; about 20%) and converted to urobilin, a yellow pigment that is excreted by the kidneys.

The iron ion is transported by a globulin plasma protein called

transferrin

transported by transferrin to the liver or spleen, where the Fe2+ then is bound to storage proteins called ferritin and hemosiderin.

Ferritin

• large water-soluble protein

• serves as the primary sttorage mechanism for ion.

Iron is stored mainly in the

• liver and spleen and it is

• transported by transferrin to the red bone marrow as needed for erythrocyte production.

Small amounts of iron, approximately ___ are lost daily in,

• 0.9 mg

• sweat

• urine

• feces

• those who are menstruating

The plasma membrane of an errthocyte has numerous molecules called

surface antigens

which project from the cell surface.

These antigens have significant implications for blood transfusion and some cases, pregnancy.

2 groups of surface antigens(that determine a persons’s blood type)

• ABO blood group

• Rh protein.

ABO blood group

is glycoproteins that are embedded in the plasma membrane of erythrocytes.

2 molecular varieties in the ABO blood group (differ in the arrangement of carbohydrates attached to the protein)

• A antigen

• B antigen

ABO blood types

• Type A: blood contains erythrocytes with surface antigen A only

• Type B: Blood contains erythrocytes with surface antigen B only

• Types AB: blood contains erythrocytes with both surface antigens A and B.

• Type O: blood contains erythrocytes with neither surface antigen A nor B.

The ABO surface antigens on erythrocytes are accompanied by specific ___ within the blood plasma.

antibodies.

An antibody is a Y-shaped protein that binds to a specific antigen that perceived as foreign to the body.

The Above blood group has both Anti A and Anti B antibodies that react with the surface antigen

A and B respectively.

• Type A blood contains anti B antibodies within its plasma

• Type B blood contains anti A antibodies within its plasma

• Type AB contains neither

• Type O blood contains both

Rh blood type

• determines by the presence or absence of the Rh surface antigen, often called either surface antigen D or Rh factor.

• When surface antigen D is present, the individual is said to be Rh positive

• when surface antigen D is not present, the individual is said to be Rh negative.

Anti-D antibodies appear in the blood only when

an Rh negative individual is exposed to Rh positive blood.

may occur in certain pregnancies where the mother is Rh negative.

Agglutination

If a person is transfused with blood of an incompatible type, antibodies in the plasma bind to surface antigens of the transfused erythrocytes, and clumps of erythrocytes bind together in a process termed agglutination.

Clumped erythrocytes can block blood vessels and prevent the proper circulation of blood

Hemolysis

a process where some or all the clumped erythrocytes may rupture.

The release of erythrocyte contents and fragments into the blood often causes

further hemolytic reactions and ultimately may damage organs. Therefore, compatibility between donor and recipient must be determined prior to blood donations and transfusions using an agglutination test.

Leukocytes

• help defend the body against pathogens

• differ from erythrocytes in that they are about 1.5 to 3 times larger in diameter

• contains a nucleus and cellular organelles

• do not contain hemoglobin

• concentration in the blood typically ranges between 4500 and 11,000 per cubic millimeter of blood.

• are motile(capable of movement within interstitial fluid) and remarkably flexible.

• most are found within body tissues

• enters the tissues from blood vessels by diapedesis

diapedesis

where leukocytes squeeze between the endothelial cells of the blood vessel walls.

Chemotaxis

a process in which leukocyte are attracted to a site of infection by the presence of molecules released by damaged cells, dead cells, or invading pathogens.

5 types of leukocytes are divided into 2 distinguishable classes

• granulocytes

• granulocytes

based upon the visible presence or absence of secretory vesicles(specific granules) in the cytosol.

Granulocytes

• neutrophils

• esoinophils

• basophils

Neutrophils

Characteristics: Nucleus is mutilobed as many as 5 lobes, systole contains natural or pale, specific granules (when stained)

Functions: phagocytize pathogens, especially bacteria, release enzymes that target pathogens

Approximate %: 50 to 70% (1800-7800 cells per microliter)

• usually remain in circulation for about 10 to 12 hours before they exit the blood vessels and enter the tissue spaces, where they phagocytize infectious pathogens, especially bacteria.

Eosinophils

Characteristics: Nucleus is bilobed, cytosol contains reddish or pink orange specific granules when stained

Functions: phagocytize antigen-antibody complexes and allergens, release chemical mediators to destroy parasitic worms

Approximate %: 1-4 (100-400 cells per microliter)

Basophils

Characteristics: Nucleus is bilobed, systole contains deep blue violet specific granules when stained

Functions: Releases histamine(vasodilator and increases capillary permeability) and heparin(anticoagulant) during inflammatory reactions

Approximate %: 0.5 to 1 (20-50 cells per microliter)

Monocytes

Characteristics: Kidney-shaped or C shaped nucleus, Nucleus is generally pale staining, abundant cytosol around nucleus

Functions: exit blood vessels and become macrophages, phagocytize pathogens (bacteria, viruses) cellular fragments dead cells and debris.

Approximate %: 2-8 (100-700 cells per microliter)

can be up to 3 times the diameter of an erythrocyte

approximately 3 days in circulation

Lymphocytes

Characteristics: Round or slightly indented nucleus (fills the cell in smaller lymphocytes), nucleus is usually dark stained, thin rim of systole surrounds nucleus

Functions: coordinate immune cell activity, attack pathogens as well as abnormal and infected cels, produce antibodies.

Approximate %: 20-40% (1000-4800)

• same size of slightly larger than an erythrocyte

• 2 categories: T-lymphocytes & B-lymphocytes

• T: mange and direct an immune response; some directly attack foreign cells and virus-infected cells

• B: stimulated to become plasma cells and produce antibodies. NK cells attack abnormal and infected cells.

Differential count/ white blood cell differential count

measure the amount of each type of leukocyte in your blood and determines whether any of the circulating leukocytes are immature.

Infection, tissue necrosis, bone marrow failure, cancers, and some other stresses to the body can affect the total ranges or percentages of specific type of leukocytes.

Leukopenia

a reduced number of leukocytes, may increase the risk of a person developing or decrease the ability to fight infection effectively.

Leukocytosis

slightly elevated leukocyte count, may be caused by a variety of factors such as a recent infection or stress.

Neutrophilia

an increase in neutrophils, associated with acute bacterial infections, acute stress, and tissue necrosis.

number will be up in the tens of thousands, up to 50,000.

Left-shifted differential

as the body tries to produce more and more neutrophils, some immature neutrophils (called band neutrophils, or band cells) enter the circulation and are detected by the differential count. Increased presence of these immature neutrophils is referred to as a left-shifted differential.

neutropenia

a decrease in neutrophils, may occur with certain anemias, drug or radiation therapy, and other causes.