5 leucocyte

LEUCOCYTE

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BLOOD AND INTERNAL BLOOD AND INTERNAL ENVIRONMENTAL ENVIRONMENTAL

HOMEOSTASISHOMEOSTASIS Blood is that part of extracellular fluid within the cardiovascular

system Blood forming

During animals’ evolution, extracellular fluid was gradually shaped from the age-old time with ocean which was mainly salty solution. At last, extracellular fluid was differentiated into plasma and interstitial fluid and blood came from plasma and cells.

The role of blood in internal environmental homeostasis

Blood, the most active component in extracellular fluid, display functions as follows:

(1) transportation;

(2) pH value buffer;

(3) temperature or thermal maintenance;

(4) immunity and defence

BLOOD COMPOSINGBLOOD COMPOSING Blood composing: plasma +

blood cells

Hematocrit:

blood cells occupies the percentage of total blood volume.

normal value

male: 40-50%

female: 37-48%

newborn: 55%

BLOOD COMPONENT (SUMMING-UP)BLOOD COMPONENT (SUMMING-UP)

TERMINOLOGY AND NORMAL TERMINOLOGY AND NORMAL VALUEVALUE

CHEMICAL COMPONENT OF CHEMICAL COMPONENT OF PLASMAPLASMA

Water: > 90%

Small molecule: 2%, it is electrolytes, nutriment, metabolic products, hormone, enzyme,etc.

Protein: 60-80 g/L, plasma protein include albumin (40-50 g/L), globulin (20-30 g/L,α1-, α2, β-, γ- ) and fibrinogen. Most of albumin and globulin made from liver. A/G and clinic.

Function of plasma protein: (1) transportation, (2) nutrition, (3) forming colloid osmotic

pressure, (4) coagulation and anticoagulation, (5) pH value buffer, (6) immunity (globulin)

CHEMICAL COMPONENT OF CHEMICAL COMPONENT OF PLASMAPLASMA

540.414蛋白质

292.32PO4-

1394.44.3K+

<0.0012.42.5Ca++

4117104Cl-

12145142Na+

细胞内液组织液血浆

540.414蛋白质

292.32PO4-

1394.44.3K+

<0.0012.42.5Ca++

4117104Cl-

12145142Na+

细胞内液组织液血浆

(Unit ： mmol/L)

H2O 90 - 91%

Plasma Interstitial fluid

Intracellular fluid

Protein

PHYSICAL AND CHEMICAL PHYSICAL AND CHEMICAL CHARACTERISTICS OF CHARACTERISTICS OF

BLOODBLOOD Specific gravity: total blood (1.050-1.060) more influenced by red blood cells;

plasma (1.025-1.030) more influenced by plasma protein; RBC (1.090-1.092) more influenced by Hb.

Viscosity: Blood relative viscosity (4~5) mainly depends on the numbers of red blood cells. Plasma relative viscosity (1.6~2.4) is mainly involved in plasma protein

Plasma osmotic pressure is 300 mmol/L or 770kPa (1) Crystal osmotic pressure results from NaCl and modulates water distribution

between inside and outside of cells. (2) Colloid osmotic pressure results from albumin and regulates water distribution

between inside and outside of capillary.

Plasma pH value is about 7.35~7.45, and usually buffer systems are NaHCO3/H2CO3 (20:1), protein salt/protein, Na2HPO4/ NaH2PO4, Hb salt/Hb, HbO salt/ HbO2, K2HPO4/ KH2PO4, KHCO3/H2CO3, etc [lungs and kidney mainly regulate Plasma pH value ].

BLOOD CELLSBLOOD CELLS

Blood cells are erythrocyte (red blood cell, RBC), leukocyte (white blood cell, WBC) and thrombocyte (platelet, P).

BLOOD CELLSBLOOD CELLS

The forming processes of erythrocyte (red blood cell, RBC), leukocyte (white blood cell, WBC) and thrombocyte (platelet, P) originating from hematopoietic stem cells are hemopoiesis.

Transfer of blood cells forming place:

yolk sac hemopoiesis (early embryo period) → liver and spleen (second embryo month) → marrow↑and liver, spleen↓ (after fourth embryo month) → marrow (fetus birth time) and liver, spleen as complementary role.

During adulthood (after 18), red marrow (flat bones, e.g. vertebra,ilium, sternum, rib, skull and long bone ending) rather than yellow marrow has hematopoietic functions.

HEMOPOIETIC PROCESSHEMOPOIETIC PROCESS

LEUKOCYTES (WBCS)

Leukocytes, the only blood components that are complete cells: Are less numerous than RBCs Make up 1% of the total blood volume Can leave capillaries via diapedesis Move through tissue spaces Normal response to bacterial or viral invasion

CLASSIFICATION AND NUMBERS OF CLASSIFICATION AND NUMBERS OF LEUKOCYTE LEUKOCYTE

Number of Leukocyte (white blood cells, WBC):

(4.0~10)×109/L

Classification: It is granulocyte (neutrophil,

eosinophil, basophil), monocyte and lymphocyte.

CLASSIFICATION AND NUMBERS OF LEUKOCYTE

TABLE. Classification and normal value of TABLE. Classification and normal value of LeukocyteLeukocyte

AbsoluteAbsolute Value (×10 Value (×1099/L) Percentage (%)/L) Percentage (%)

Total numbers of leukocytes 4.0~10.0 Total numbers of leukocytes 4.0~10.0 Neutrophil (bacilliform nucleus) 0.04~0.5 1~5 Neutrophil (bacilliform nucleus) 0.04~0.5 1~5 Neutrophil (foliiform nucleus) 2.0~7.0 50~70 Neutrophil (foliiform nucleus) 2.0~7.0 50~70 Eosinophil 0.02~0.5 0.5~5 Eosinophil 0.02~0.5 0.5~5 Basophil 0.0~0.1 0~1 Basophil 0.0~0.1 0~1 Monocyte 0.12~0.8 3~8 Monocyte 0.12~0.8 3~8 Lymphocyte 0.8~4.0 20~40 Lymphocyte 0.8~4.0 20~40

For Clinic Use

PHYSIOLOGICAL CHANGES IN PHYSIOLOGICAL CHANGES IN NUMBERS NUMBERS

OF LEUKOCYTEOF LEUKOCYTE Newborn: Number is higher, 15×109/L, after birth 3 or 4 days to 3

months, being about 10×109/L, mainly, neutrophil, 70%; secondarily, lymphocyte.

Circadian changes: Number of WBC is more in the afternoon than in the morning.

Food taking, ache and mood excitation: Number of WBC is remarkably higher.

Heavy exercise and laboring: Increasing numbers, about 35×109/L, return to original level after action stop.

Terminal pregnancy of female: Numbers changes in 12~17×109/L, and during parturition, 34×109/L, and after parturition 2~5 days, number return to original level.

CLASSIFICATION OF LEUKOCYTES: 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

NEUTROPHILS

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 bacterial slayers

PHYSIOLOGICAL PHYSIOLOGICAL CHARACTERISTICSCHARACTERISTICS AND FUNCTIONS OF WBC AND FUNCTIONS OF WBC

Another name, polymorphonuclear, PMN, 6~8 h in the vessels, diapedisis, chemotaxis and phagocytosis (using its hydrolyzed enzyme)

Function: It plays a very important role in nonspecific cellular immunity system which is against pathogenic microorganism, such as bacteria, virus, parasite, etc.

Clinic relation: Number of neutrophil greatly increase occurring in acute inflammation and earlier time of chronic inflammation. number decrease of neutrophil will result in poor resistibility and easily suffering from infection.

NEUTROPHILS

Table 18.2.1

NEUTROPHILS

Table 18.2.2

EOSINOPHILS

Eosinophils account for 1–4% of WBCs Have red-staining, bi or tri-

lobed 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

Lessen the severity of allergies by phagocytizing immune complexes

PHYSIOLOGICAL PHYSIOLOGICAL CHARACTERISTICSCHARACTERISTICS

AND FUNCTIONS OF WBC AND FUNCTIONS OF WBC Circadian changes: Its number is lower in the morning

and higher at night.

Function:

1. It limits and modulates the effects of basophil on fast

allergic reaction.

2. It is involved in immune reaction against worm with

opsonization.

Clinic relation: Its number increase when person suffers

from parasite infection or allergic reaction.

BASOPHILS

Account for 0.5% of WBCs and: Have U or Sshaped nuclei with

two or three conspicuous constrictions

Are functionally similar to mast cells

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

that acts as a vasodilator and attracts other WBCs


AND FUNCTIONS OF WBC AND FUNCTIONS OF WBC Circulatory time: 12 hours

Basogranules contain heparin, histamine, chemotactic factors and chronic reactive material for allergic reaction.

Function: It is also involved in allergic reaction. 1. Heparin serves as lipase cobase and speeds up fatty decomposition. 2. Histamine and chronic reactive material increase permeability of capillary and contract bronchia smooth muscle, and result in allergic reaction such as measles, asthma. 3. Eosinophil chemotactic factor A released by basophil can attract eosinophil collection and modify eosinophil function.

AGRANULOCYTES

Agranulocytes – lymphocytes and monocytes: Lack visible cytoplasmic granules Are similar structurally, but are functionally distinct and

unrelated cell types Have spherical (lymphocytes) or kidney-shaped

(monocytes) nuclei

LYMPHOCYTES

Have large, dark-purple, circular nuclei with a thin rim of blue cytoplasm

Found mostly enmeshed in lymphoid tissue (some circulate in the blood)

There are two types of lymphocytes: T cells and B cells T cells function in the immune

response B cells give rise to plasma cells,

which produce antibodies


AND FUNCTIONS OF WBCAND FUNCTIONS OF WBC Classification: It can be separated into T- Lymphocyte and

B- Lymphocyte.

Function:

1. Lymphocytes serve as a nuclear role in immune

responsive reaction.

2. T- Lymphocytes involved in cellular immunity.

3. B- Lymphocytes involved in humoral immunity.

Clinic relation: Numbers increase of lymphocytes occur in

chronic inflammation and late time of infection.

MONOCYTES

Monocytes account for 4–8% of leukocytes They are the largest leukocytes They have abundant pale-blue

cytoplasms They have purple staining, U- or

kidney-shaped nuclei They leave the circulation, enter

tissue, and differentiate into macrophages

Macrophages: Are highly mobile and actively

phagocytic Activate lymphocytes to mount

an immune response

PHYSIOLOGICAL CHARACTERISTICSPHYSIOLOGICAL CHARACTERISTICSAND FUNCTIONS OF WBCAND FUNCTIONS OF WBC

Its body is large, diameter about 15~30 µm without granule

Function:

1. It contains many nonspecific lipase and displays the

powerful phagocytosis.

2. As soon as monocytes get into tissue from blood , it change

name called macrophage activating monocyte- macrophage

system to release many cytokins, such as colony stimulating

factor (CSF), IL-1, IL-3, IL-6, TNFα, INF-α,β ,etc.

3. Cytokins induced by monocyte may modulate other cells

growth. 4. Monocyte- macrophage system plays a very important role in specific immune responsive induction and regulation.

Genesis of leukocytes:

1.The granulocytes and monocytes are formed only in bone marrow 2.Lymphocytes and plasma cell: Produced in various lymphogenous organs

Lymph glandsSpleenThymusTonsilPeyer’s patch

Megakaryocytes are also formed in bone marrow and are parts of myelogenous group of bone marrow cells

Life span of WBC:

The main reason white blood cells are present in the blood is to be transported from bone marrow or lymphoid tissue to the area of body where they are needed

1.Granulocytes: Life of granulocytes once released from bone marrow is normally 4-8 hours in circulating blood and another 4-5 days in tissue (in serious infection total life span is shortened)

2.Monocytes: Circulate in blood for 10-20 hours and reach to tissue. In tissue, they swell to much larger in size and become tissue macrophage. These tissue macrophages can live for months or even years unless they are destroyed by performing phagocytic function

3.Lymphocytes: Lymphocyte enters the circulatory system continually along with drainage of lymph from lymph node and other lymphoid tissue Then after a few hours, they pass back into tissue by diapedesis and then reenter the lymph and return either to lymphoid tissue or to blood again and again, thus there is continual circulation of lymphocyte throughout the body

The lymphocytes have life span of weeks, months, or even years but this depend on body need for these cells

LEUKOPOIESIS, REGULATION AND BREAKAGE

Leukopoiesis, differentiation and growth are influenced by hemopoietic growth factor, HGF which are glycoprotein secreted by lymphocyte, monocyte- macrophage, fibrous cell and endothelial cell.

Colony stimulating factor, CSF, such as GM-CSF, G-CSF, M-CSF, Multi-CSF (IL-3) also influence Leukopoiesis.

Life span: several hours to 3 or 4 days.

Leukocyte breakage: site are liver, spleen and lymphatic node.

Pus or purulence forming

PRODUCTION OF LEUKOCYTES

Leukopoiesis is hormonally stimulated by two families of cytokines (hematopoetic factors) – interleukins and colony-stimulating factors (CSFs) Interleukins are numbered (e.g., IL-1, IL-2), whereas CSFs

are named for the WBCs they stimulate (e.g., granulocyte-CSF stimulates granulocytes)

Macrophages and T cells are the most important sources of cytokines

Many hematopoietic hormones are used clinically to stimulate bone marrow

FORMATION OF LEUKOCYTES

All leukocytes originate from hemocytoblasts Hemocytoblasts differentiate into myeloid stem cells

and lymphoid stem cells Myeloid stem cells become myeloblasts or

monoblasts Lymphoid stem cells become lymphoblasts Myeloblasts develop into eosinophils, neutrophils,

and basophils Monoblasts develop into monocytes Lymphoblasts develop into lymphocytes

36


Figure 18.11.1


Figure 18.11.2


Figure 18.11.3

40

Function of WBC

1.Phagocytosis: By this process, WBC engulf bacteria, other foreign particles and microorganism

2.Antibody formation: Lymphocyte produce antibody and play an important role in defensive mechanism of body

3.Act as scavenger: It act as scavenger so help in removing debris of dead and devitalized tissue

4.Formation of fibroblasts: Lymphocytes may be converted into fibroblast in the area of infection and thus help the process of repair

5.Act to prevent clotting: Basophils secret heparin, which prevent intravascular clotting

6.Help to prevent allergy: Eosinophils

Defensive properties of Neutrophils and Macrophages

Neutrophils and macrophages attack and destroy invading bacteria, viruses and other harmful agents

1.Neutrophils are mature cells so can attack and destroy foreign substance in circulating blood

2.Macrophages:They begin life as monocyte in blood (immature cells)

↓They enter into tissue

↓They swell up as much as five folds and also acquire large number

of lysosomes↓

These are now called macrophages and they are capable of combating disease agent

Properties of WBC:

1. Diapedesis: It is the process by which WBC comes out through the pores of blood

vessels. The size of pores is smaller than size of WBCMechanism:

WBC comes to vessel wall (margination)↓

Then small portion of cell slides through the pore at time, the portion sliding

through being momentarily constricted to size of pore↓

This process continue until finally WBC comes out of blood vessels

2. Amoeboid movement: It is special type of movement by which WBC (Neutrophils and

macrophages) moves toward damage tissue Velocity of movement: 40 micron/min

Mechanism:Cells protrude pseudopodia from one end of cell

↓These pseudopodium projects far out away from cell body

↓Then remainder of cell also moves toward pseudopodium

3.Chemotaxis:

Many different chemical substances in the tissue cause both Neutrophils and Macrophages to move toward the source of chemical. So this phenomena by which WBC are attracted toward the site where these chemical substances are formed is called “Chemotaxis.” These chemical substances are called chemotaxic substance. When tissue becomes inflamed it releases Chemotaxic substance

The chemotaxic substances include:a.Bacterial toxinsb.Degenerative products of inflamed tissue themselvesc.Several reaction product of complement complexd.Several reaction products caused by plasma clotting in the

inflamed area

•Chemotaxis depends on conc gradient of chemotactic substance.•Chemotaxis is effective up to 100 micrometer away from an inflamed tissue•No tissue area is more than 50 micrometer away from capillary. so chemotactic signal can easily move large number of WBC from capillaries into inflamed area

4.Phagocytosis: Cellular ingestion of offending agent It is the process by which WBC (Neutrophils and macrophages) engulf foreign particles

Phagocytosis is selective so that normal cells and structure of body are not phagocytised,this selectivity of phagocytosis depends upon:

A.Roughness of surface make particle more prone to be phagocytised Natural structure in tissue have smooth surface so resist phagocytosis

B.Natural substance of boy have protective protein coat (negative charge) which repel phagocytosis Dead tissue and foreign particle have no protective coat (positive charge) which make them subject to phagocytosis

C.Body has s specific means of recognizing certain foreign substanceThe immune system of our body develops antibody against infectious agent like bacteria. These antibodies attach to bacterial membrane and make bacteria susceptible to be phagocytised. For this, antibody binds with C3 products of complement cascade. This C3 molecule then attach themselves to receptor on WBC, thus initiating phagocytosis. This entire process is called “OPSONIZATION.”

Mechanism of phagocytosis:

1.Recognition and attachment: Neutrophils and macrophages first recognize the particle to be ingested and attach on their surface

2.Engulfment: After attachment, they project pseudopodia in all direction around the particle and enclose it completely and after that forms phagocytic vesicle (phagosome) inside the cytoplasm

3.Killing and/or degradation: After engulfing, most organisms are destroyed within phagosome by lysosomal enzyme and bactericidal agent a. Lysosomal enzyme:

Neutrophils and macrophages have proteolytic enzymeLysosome of macrophages have in addition large amount of lipaseThese help to kill most of bacteria

b. Bactericidal agent: Neutrophils and macrophages contain bactericidal agent that kill most bacteria even when the lysosomal enzyme fail to digest them.

E.g. oxidizing agent: Superoxide (O2-)

Hydrogen peroxide (H2O2)Hydroxyl ion(OH-)Hypochlorite (products formed by reaction between

H2O2 and chloride ion)

Even small quantity of any of these agents is lethal to most bacteria

Mechanism of phagocytosis:

Reticuloendothelial system/monocyte-macrophage system/tissue macrophage system:

The combination of monocyte, mobile macrophages, fixed tissue macrophages and a few specialized endothelia cells in the bone marrow, spleen, and lymph node is called the reticuloendothelial system Origin:

•All or almost all these cells originate from Monocytic stem cell

•Large portion of monocyte enters the tissue and after becoming macrophages, become attached to the tissue and remain attached for months or even years until they are called to perform specific protective function. These tissue macrophages have same capabilities as mobile macrophage. They can also become mobile macrophages i.e. they can break away from their attachment and become mobile macrophage when appropriately stimulated. •So this system is a generalized phagocytic system located in all tissues. Tissue macrophages in various tissues differ in appearance and so are known by different names

Cells of tissue macrophage

Organ Cell nameLiver Kupffer cells

CNS Microglia

Kidney Mesangial cells

Bone Osteoclast

Lymph node, spleen, bone marrow

Reticular cells

Skin and subcutaneous tissue

Histiocytes clasmatocytes

Lungs Alveolar macrophage

Pleura, peritoneum, pericardium (

Macrophage of serosal cavities

LEUKOCYTE DISORDERS: LEUKEMIAS

Leukemia refer to cancerous conditions involving white blood cells

Leukemias are named according to the abnormal white blood cells involved Myelocytic leukemia – involves myeloblasts Lymphocytic leukemia – involves lymphocytes

Acute leukemia involves blast-type cells and primarily affects children

Chronic leukemia is more prevalent in older people

**Leukocytosis – WBC count over 11,000 per cubic millimeter

LEUKEMIA

Immature white blood cells are found in the bloodstream in all leukemias

Bone marrow becomes totally occupied with cancerous leukocytes

The white blood cells produced, though numerous, are not functional

Death is caused by internal hemorrhage and overwhelming infections

Treatments include irradiation, antileukemic drugs, and bone marrow transplants

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