Introduction to Blood

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					                 Introduction to Blood

                  Learning Objectives



The student should be able to :


1. Define what is hematology?


2. Know what blood is & its development.


3. Describe the composition of blood.


4. Ought to know the formed elements of blood.


5. What is plasma?


6. Must know the characteristics of different types of blood
cells.


7. Explain the cell morphology.




8. Must make out comparison of RBCs, WBCs and Platelets.


9. Must be familiar with functions of blood.
10. Make out what is inflammation and its types.



11. Explain clinical signs of inflammation.



12. Clarify the cellular events of inflammation.


13. Identify key characteristics of immune responses.


14. Compare innate and specific immunity.



15. Explain how immunity is acquired.
                          Lecture Outline
                      Introduction to Blood


What is hematology?


"Hematology" comes from the Greek words haima, meaning blood, and
logos, meaning study or science. So, hematology is the science of
blood.



Blood :

    Blood is a complex fluid tissue. It circulates in a closed system

         of blood vessels and heart.

        The normal adult total circulatory blood volume is about 8% of

         the total body weight (5600 ml in 70 kg man).




The Blood Throughout Life :

    First blood cells develop with the earliest blood vessels.

    Mesenchyme cells cluster into blood islands.

    Late in the second month

             Liver and spleen take over blood formation.

    Bone marrow becomes major hematopoietic organ at month 7.




COMPOSITION OF BLOOD :

    Blood is the body’s only fluid tissue
   It is composed of liquid plasma and formed elements

   Formed elements include:

         Erythrocytes, or red blood cells (RBCs)

         Leukocytes, or white blood cells (WBCs)

         Platelets

   Hematocrit – the percentage of RBCs out of the total blood

     volume



A centrifuge separates blood into two components.




Formed Elements:

   Erythrocytes, leukocytes, and platelets make up the formed

     elements

         Only WBCs are complete cells

         RBCs have no nuclei or organelles, and platelets are just

            cell fragments

   Most formed elements survive in the bloodstream for only a few

     days
   Most blood cells do not divide but are renewed by cells in bone

     marrow




Blood plasma :

   Blood plasma contains over 100 solutes, including:

         Proteins – albumin, globulins, clotting proteins, and

           others

         Lactic acid, urea, creatinine

         Organic nutrients – glucose, carbohydrates, amino acids

         Electrolytes – sodium, potassium, calcium, chloride,

           bicarbonate

         Respiratory gases – oxygen and carbon




Characteristics of different types of blood cells :


   RBCs: contain red haemoglobin which enables RBCs to carry

     oxygen and some carbon dioxide.



   WBCs: lymphocytes & phagocytes, protect us from diseases.



   Platelets: broken cell fragments, help in blood clotting.
Erythrocytes :

   7-8 m diameter

   Biconcave disc shape

        Inc. surface area

        Inc. efficiency for diffusion of O2 & CO2

        Structure

        Plasma membrane

        Cytoplasm

        Hemoglobin

        Binds O2 & CO2

        No nucleus or organelles

        Immature version has nucleus and is called a reticulocyte.

        Flexible

        Elastic

        100-120 day life span

        Originate in bone marrow.




Platelet Count :


   Normal count is 140,000 to 440,000/mm3

   Life span of about 10 days

   Low platelet counts (thrombocytopenia) cause excessive bleeding

   Thrombycytopenia is common with the use of heparin, DIC,

    bone marrow disease, liver failure and sepsis.
Cell Morhphology


The Neutrophils:


   Segmented neutrophil (40-70% of WBCs)
   Life span of about 10 days

   Moves from bone marrow to blood to tissues

   Mature more quickly under stressful conditions

   Primary defense for bacterial infections.



The Basophils :


   Mature basophil
   Least common of WBCs (< 2%)

   Nucleus does not always segment

   Increase in response to same conditions that cause eosinophils

     to respond.



The Monocytes :


   Also not common in circulating blood
   Stay in blood for about 70 hours

   Become macrophages in tissue and live for several months or

     longer
The Lymphocytes :



   May mature into B or T cells

   Main function is antigen recognition and immune response

   Life span quite varied (up to two years)

   Can pass back and forth between blood



Lymphocytes: B & T types :



   B cells are not only produced in the bone marrow but also

     mature there.

   However, the precursors of T cells leave the bone marrow and

     mature in the thymus (which accounts for their designation




Types of Lymphocytes :


   B lymphocytes (or B cells) are most effective against bacteria &
     their toxins plus a few viruses
   T lymphocytes (or T cells) recognize & destroy body cells gone

     awry, including virus-infected cells & cancer cells.

   T cells come in two types: helper cells and suppressor cells;

     normally the helper cells predominate.
A comparison of RBCs, WBCs and Platelets


                Red blood           White blood
                                                         Platelets
                   cells                    cells
1. Site of    formed in bone

formation         marrow,          formed in bone
                                                      formed in blood
                  lifespan:           marrow or
                                                          marrow
                 4 months              thymus


2. Shape                                              irregular shape,
                                     phagocytes:
                                                        no nucleus,
              biconcave discs,     irregular, lobed
                                                       tiny pieces of
                no nucleus,           nucleus &
                                                      cell fragments,
                 red colour            granular
                                                         no colour
                                      cytoplasm



3. Size                             some large &
                                                          tiny cell
                small in size        some small
                                                        fragments

4. Number
                                    7,000 /mm3        250,000/mm3
              5,000,000/mm3



5. Function                       phagocytes kill
                  contain         pathogens &
              haemoglobin to      digest dead
               carry oxygen       cells.lymphocytes
                                                         for blood
              from lungs to all   produce
                                                          clotting
               parts of body      antibodies for
                                  killing
                                  pathogens.
Inflammation:

Inflammation is the complex biological response of vascular tissues
to harmful stimuli, such as pathogens, damaged cells, or irritants.

It is a protective attempt by the organism to remove the injurious
stimuli as well as initiate the healing process for the tissue.


Characteristics of Inflammation :

        Vasodilation of the local blood vessels, with consequent
          excess local blood flow.
        Increased capillary permeability with leakage of large
          quantities of fluid into the interstitial spaces.
        Clotting of fluid in the interstitial spaces because of
          excessive amounts of fibrinogen and other proteins leaking
          from the capillaries.
        Migration of large numbers of granlocytes and monocytes
          into the tissue.
        Swelling of the tissue cells.




Some tissue products that cause Inflammation are :

      Hitamine.
      Bradykinin.
      Serotonin.
      Prostaglandins.
      Reaction products of the complement system.
      Reaction products of the blood – clotting system.
      Lymphokines released by sensitized T cells.
  WALLING – OFF EFFECT OF INFLAMMATION :

  The tissue spaces and the lymphatics in the inflamed area are
  blocked by fibrinogen clots so that fluid barely flows through the
  spaces.

  This process delays the spread of bacteria or toxic products.




MACROPHAGE AND NEUTROPHIL RESPONSE DURING
INFLAMMATION:

LINES OF DEFENSE:

   First line of Defense:

                       The tissue macrophages.


   Second line of defense:

                     Neutrophil invasion of the inflamed area.


   Third line of defense:

              A second macrophage invasion of the inflamed area.


   Fourth line of defense.

            Increased production of granulocytes and monocytes by
  the bone marrow.
FEEDBACK CONTROL OF THE MACROPHAGES AND NEUTROPHIL

RESPONSES TO INFLAMMATION :


   Five factors play dominant roles in the control of macrophage –

   neutrophil response to inflammation :


      Tumor Necrosis Factor (TNF )

      Interlukin – 1 ( IL-1 )

      Granulocyte – monocyte colony stimulating factor ( GM – CSF )

      Granulocyte colony stimulating factor ( G – CSF )

      Monocyte colony stimulating factor.


The feedback meachnism begins with tissue inflammation and then

proceeds to formations of defensive white blood cells and finally

removing the cause of inflammation.


Clinical Signs of Inflammation

Heat (calor) - fever, local warmth

Erythema (rubor) - redness in involved area

Swelling (tumor) - mainly edema fluid

Pain (dolor)

Loss or decrease of function. (functio laesa)




The hallmark of acute inflammation is increased vascular permeability
leading to edema.
Immunity:


Immune responses are generally subdivided into two categories:

           Innate (or natural) and

           Antigen specific (or "acquired").



Innate immune responses:

            All of these are Antigen non-specific immune mechanisms.

They include,


     Phagocytosis and digestion of pathogen (ie. By neutrophil;

      monocyte/macrophage, eosinophil )

     Increased production or activation of Ag non-specific soluble

      proteins such as acute phase reactants, complement cascade,

      interferon, nitric oxide or lysozyme

     Natural killer cells and T cells (cytotoxic, but Antigen non-

      specific) make cytokines but exhibit very little variability in their

      receptor for Antigen.


Specific     Immunity         (acquired   or     adaptive     immunity):

Ag specificity, self/non-self discrimination and memory are its

main hallmarks.

It accomplishes this by mechanisms that are,


     Humoral       (Antibody:   IgG,   IgA,    IgM,   IgE)   made   by   B

      cells/plasma cells
        Cell mediated: Cytotoxic T cells, helper T cells.




The specific response exhibits a wide diversity of different effector

mechanisms aimed at destruction or localization of pathogens. All of

these share the characteristics of


            (i)       recognizing each Antigen with great specificity and

            (ii)      memory.


Generation of the cells responsible for the immune response involves a

process of self vs. non-self discrimination, where Antigens considered

"self"    are      not    attacked   (except     inappropriately,   such   as   in

autoimmunity). ANY molecule that is "non-self" triggers an immune

response, regardless of whether it is a pathogen or not.


Partnership               between    innate       and       acquired    immune
responses:

These are not two independent, redundant pathways to protection.

Rather,            they     form     an        integrated     defense      system.



Examples of integration include,


1. Antibodies bind to granulocytes to confer specificity on Antigen

non-specific cells in their killing (i.e. eosinophils).
2. Cytokine production generated during the innate response help

determine the type of specific response that develops (enhancing

Antibody production vs stimulating more cytotoxic cells)


3. Inflammation brings Antigen specific cells to the site, promoting

expansion of the Antigen-specific component of the response.




Immunity acquired by:


      Exposure to Antigen/potential pathogens

      Skin, Gut and other physical barriers to entry, mechanical

       defenses (cough, etc)

      Upon Antigen entry: Innate immune response (phagocytosis,

       soluble proteins, NK cells depending on the Ag in question)

       localizes Ag, attempts to lyse it and/or phagocytose it. This

       leads to,

      Generation of inflammatory response. More intense innate

       immunity due to recruitment of more monocytes, polymorphs

       and

      Activation    of   specific   immunity:     Interactions   of   T

       lymphocytes with "Ag presenting cells" and B lymphocytes,

       leading to induction of specific immune responses.

      These include, T cell activation (hence cytokine synthesis,

       cytotoxicity) and Antibody formation by B cells/plasma cells.
Active vs. Passive immunity

  Active immunity :

     Results from natural (or vaccine induced) exposure to a

      pathogen.

     It is stronger, longer lasting, more diverse and usually results

      in memory but it takes time to fully develop.




  Passive immunity :

     Refers to transfer of Antibody maternally (in utero, colostrum) or
      for specific clinical purposes.



  The advantages:

   Passive immunity is intense and immediately effective ( several
  days to months for development of a full immune response).



  The disadvantages:

   It is generally of short duration unless additional passive Antibody
  is provided. Importantly, it does not activate the host's own
  immune response, so no memory or lasting protection develops.
   FUNCTIONS OF BLOOD :


   A. Transport:


   1. Oxygen         - By RBCs in the form of oxyhaemoglobin




  2. Carbon dioxide

            - By plasma in the form of hydrogen carbonate ions



  3. Food

         - Carries absorbed food substances such as glucose from the

small intestine to various parts of the body.



  4. Urea

        – produced in the liver, dissolves in plasma, is carried to the

kidney and excreted in the urine.



5. Hormones – Secreted by endocrine glands into blood for transport.



6. Antibodies – Carried by blood for body defence.



7. Heat –

   - produced during respiration in muscles and liver and transported

to other parts of the body.
B. Blood clotting:


  Prevent excessive bleeding by clot formation.




C. Regulation of body temperature




D. Defence against infection


   1. Phagocytes: engulf and kill pathogens

   2. Lymphocyte: produce antibodies to kill pathogens.