The Blood

Chapter 11

The three types of cellular elements in the blood are: erythrocytes, leukocytes, and platelets. The plasma is the liquid part of

the blood. The plasma is 90% water.

The hematocrit is the percentage of total blood occupied by formed elements. ~42% in women & ~45% in men. About 99% of

the hematocrit is erythrocytes.

About 1% of cells are leukocytes

Packed cellvolume, orhematocrit

Plasma = 55% of whole blood

Buffy coat <1%Platelets &White blood cellsRed blood cells = 45% of whole blood

Plasma is a transport medium. It transports inorganic substances such as Na+ & Cl-. Plasma proteins compose 6 to 8 percent of the plasma’s total

weight & have numerous functions.Albumins establish an osmotic gradient between the blood

and interstitial fluid. Other proteins buffer pH changes.The globulins (alpha & beta,) have roles ranging from blood

clotting to transport. The gamma globulins function in immunity as antibodies.Fibrinogen is a key factor in blood clotting.

Other substances carried in the plasma include nutrients, waste products, dissolved gases, and hormones.

Erythrocytes transport oxygen. Erythrocytes are also called red blood cells

(RBCs).They transport O2, to a lesser extent, CO2 and H+ Their concentration is about 5 x 109 per ml

Also read as 5 x 106 / mm3.

8 m

2 m

Its flat, biconcave, disc shape It has a large surface area

& is thin. RBCs lack a nucleus, organelles,

& ribosomes. It is mainly a bag of hemoglobin.Has a lifespan of ~120 days

The plasma membrane of the erythrocyte is flexible allowing it to slide through a capillary.

Hemoglobin is a molecule consisting of two parts.The globin is four, folded polypeptide chains.The heme part is inorganic. Each of its four iron atoms can combine

with one molecule of O2 gas. Hemoglobin can also combine with CO2,

H+, CO, NOHemoglobin can buffer pH by

binding with hydrogen ions.The erythrocyte contains glycolytic enzymes. Its contains carbonic anhydrase: converts CO2 HC03-.

The bone marrow produces erythrocytes in children and adults. An erythrocyte in the circulation cannot reproduce,

as it lacks a nucleus. Erythropoiesis (erythrocyte production) is the

production of new red cells, replacing the worn-out cells in the circulation.

Pluripotent stem cells in the red marrow differentiate into the different types of blood cells.

Regulatory factors act on hemopoietic (blood-producing) red marrow to govern the type and number of cells produced and discharged into the circulation.

Erythropoiesis is controlled by erythropoietinThe average life span of an erythrocyte is 120 days. The final demise of old erythrocytes is in the spleen. The number of erythrocytes normally remains steady.

Cell production equals cell death. However, a low level of oxygen delivery to the tissues stimulates an

increased rate of erythrocyte production. If O2 delivery to the tissues is decreased, the kidneys detect this and

increase the output of erythropoietin. Erythropoietin induces new RBC production Erythropoietin can be produced synthetically Reticulocytes are released from the bone marrow into the when

circulation erythropoiesis is rapid. Reticulocytes are immature erythrocytes.

Erythropoietin (EPO) MechanismImbalance

Reduces O2 levels in blood

Erythropoietin stimulates red bone marrowEnhanced

erythropoiesis increases RBC count

Normal blood oxygen levels Stimulus:, decreased availability of O2 to tissue, or increased tissue demands for O2

Imbalance

Start

Kidney (and liver to a smaller extent) releases erythropoietin

Increases O2-carrying ability of blood

Anemia is a reduction below the normal capacity in the blood to carry oxygen. Types of anemia. Nutritional anemia is caused by a dietary deficiency of a factor

needed for erythropoiesis (iron).Pernicious anemia is due to the inability to absorb sufficient vitamin

B 12 from the digestive tract. This deficiency is due to the lack of the intrinsic factor

Aplastic anemia is due to the failure of the bone marrow to make adequate numbers of RBCs.

Renal anemia is due to kidney disease. Hemorrhagic anemia is due to the loss of significant amounts of

blood.Hemolytic anemia is due to the rupture of many RBCs.

Sickle cell cells are fragile

Polycythemia is an excess in circulating erythrocytes. Primary polycythemia is caused by an tumorlike condition in the bone marrow.

Secondary polycythemia is an erythropoietin-induced adaptive mechanism to improve the oxygen-carrying capacity in the blood.

Dehydration plasma decrease relative to hematocrit.

Anemia PolycythemiaDehydration

( =

Normal

Hem

ato

crit

30%45%

70%

70%Plasma

Erythrocytes

Leukocytes are the mobile units of the body’s immune system.

Leukocytes are also called white blood cells (WBCs)

They function mainly as defense & housekeeping agents They defend against the invasion of pathogens. They identify cancer cells. They remove the body’s litter by phagocytosis.

They can leave the circulation and go to the sites of invasion and tissue damage.

Leukocytes (WBCs) Leukocytes the only blood components that

are complete cells: Includes:

GranulocytesNeutrophils, Esinophils & Basophils

AgranulocytesLymphocytes

T & B cells as well as NK cellsMonocytes

Can leave capillaries via diapedesis and move through tissue spaces

Make up 1% of the total blood volume (5-10 X 103 cells per mm3)

They are produced from pluripotent stem cells in the bone marrow. These cells can differentiate and proliferate into different cell lines, producing the different kinds of white blood cells.

Granulocytes Granulocytes – neutrophils, eosinophils, and

basophils Contain cytoplasmic granules that stain

specifically (acidic, basic, or both) with Wright’s stain

Are larger and usually shorter-lived than RBCs Have lobed nuclei Are all phagocytic cells

Normally about two-thirds of the leukocytes in the blood are granulocytes. Their rates change depending on the changing

defense needs of the body.

Neutrophils have two types of granules that: Take up both acidic and

basic dyes Give the cytoplasm a lilac

color Contain peroxidases,

hydrolytic enzymes, and defensins (antibiotic-like proteins)

Neutrophils are our body’s bacteria slayers

Neutrophils

Eosinophils account for 1–4% of WBCs Have red-staining, bilobed

nuclei connected via a broad band of nuclear material

Have red to crimson (acidophilic) large, coarse, lysosome-like granules

Lead the body’s counterattack against parasitic worms & protozoans

Can induce allergeric response via release of leukotrienes in response to to bound IgE

Eosinophils

Account for 0.5% of WBCs and:Have U- or S-shaped nuclei

with two or three conspicuous constrictions

Are functionally similar to mast cells—promote inflammation

Have large, purplish-black (basophilic) granules that contain histamineHistamine – inflammatory chemical that

acts as a vasodilator and attracts other WBCs (antihistamines counter this effect)

Basophils

Agranulocytes – lymphocytes and monocytes: Lack visible cytoplasmic granules Have spherical (lymphocytes) or

kidney-shaped (monocytes) nuclei

Agranulocytes

Account for 25% or more of WBCs and:Have large, dark-purple,

circular nuclei with a thin rim of blue cytoplasm

Most are found mostly enmeshed in lymphoid tissue (some circulate in the blood)

There are two types of lymphocytes: T cells and B cellsT cells direct cell to cell killing and cytokine

production B cells give rise to plasma cells, which

produce antibodies

Lymphocytes

Monocytes account for 4–8% of leukocytes They are the largest

leukocytesThey have abundant

pale-blue cytoplasmsThey have purple-staining, U- or kidney-

shaped nucleiThey leave the circulation, enter tissue,

and differentiate into macrophagesMacrophages:

Are highly mobile and actively phagocyticActivate lymphocytes to mount an immune

response

Monocytes

The leukocytes production. The bone marrow

can greatly alter relative percentage of WBC produced.

Platelets (thrombocytes) function in hemostasis. They are cell fragments derived from

megakaryocytes. They average 2.5 x 108 per ml. Their range is

also reported as 1.5 – 3.5 x 105 per cubic mm. They remain functional for about 10 days. The hormone thrombopoietin increases the

number of megakaryocytes. Their overall production is not well understood.

In bonemarrow

Incirculation

Undifferentiatedpluripotentstem cell

Myeloid stem cell Lymphoid stem cell

Megakary-ocytes

Erythrocyteprecursors

Granulocyteprecursors

Monocyteprecursors

Lymphocytes inlymphoid tissues

LymphocytesMonocytesGranulocytesErythrocytesPlatelets

Hemostasis prevents blood loss from damaged blood vessels.The first two steps to stop escaping blood from a vessel

are:1) vascular spasm - This reduces blood flow through a

damaged vessel. 2) platelet plugging - An aggregation of platelets forms a

plug. Platelets aggregate on contact with exposed collagen in

the damaged wall of a vessel. The platelet plug seals a break in a vessel.

ADP stimulates platelets to become sticky. Other substances from the endothelium of a blood vessel

inhibit platelet aggregation, keeping it open.

Platelets

Vessellumen

Vesselwall

ADP

Prostacyclin& nitric acid

Normal endothelium

Inhibits plateletaggregation

Normal endothelium

Prostacyclin& nitric acid

CollagenExposed collagenat site of

vessel injury

Aggregatingplatelet plug

The third step to block escaping blood from an injured blood vessel is clot formation. This reinforces the platelet plug and converts

the blood to a gel in the area of the vessel damage.

The ultimate step in clot formation is the conversion of fibrinogen (large and soluble plasma protein) into fibrin (thread-like protein). This conversion is catalyzed by thrombin.

Fibrin threads trap RBCs, forming a clot. This clot is a meshwork strengthened by

cross-linkage from factor XIII.

Plateletfactor 3 (PF3)

Plateletaggregation

Secretes

EnhancesOther steps in cascade

Prothrombin ThrombinActivates

Stimulatesconversion

Fibrinogen(soluble)

Fibrin:loosemesh

Factor XIII

Activates

Fibrin:tightmesh

The clotting cascade is a series of steps involving twelve clotting factors.

Pathway for clot formation in vessels

Pathway for clot formation in tissuesAmplification occurs in the clotting

process. One molecule can activate one

hundred molecules in the next step

Vessel damage

Exposed collagen

Plateletaggregation

Activation of

factorXII

Activationof thrombin

Activation of factors

Formation of fibrin mesh

Seal damaged vessel

PF3

Clottingcascade

Hageman factor

Exposed collagen activates both the clotting cascade as well as platelet aggregation

FastActivation of

factor XII(Hageman factor)

Fast

Clotformation

Plasminactivation

Dissolutionof clot

Slow

(Cascade of reactions)

(Cascade of reactions)

Plasmin eventually breaks down the clot making it a temporary structure

Other facts on blood clotting include: Clot retraction occurs after the clot is formed. The clot is not a permanent solution for injury to a vessel.

Fibroblasts form scar tissue for vessel repair. The clot is slowly dissolved by the enzyme plasmin.

It is made in the liver from plasminogen. Macrophages remove the products of clot dissolution. tPA prevents inappropriate clot formation. Inappropriate clotting can produce a thromboembolism. Causes of this include roughened surfaces on a vessel. Hemophilia is a condition responsible for excessive bleeding. It is due to a deficiency of factor VIII