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, bonemarrow 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 cells / White blood cells / Platelets
1. Site of
formation / formed in bone marrow, lifespan:
4 months / formed in bone marrow or thymus / formed in blood marrow
2. Shape / biconcave discs,
no nucleus,
red colour / phagocytes: irregular, lobed nucleus & granular cytoplasm / irregular shape,
no nucleus,
tiny pieces of cell fragments,
no colour
3. Size / small in size / some large & some small / tiny cell fragments
4. Number / 5,000,000/mm3 / 7,000 /mm3 / 250,000/mm3
5. Function / contain haemoglobin to carry oxygen from lungs to all parts of body / phagocytes kill pathogens & digest dead cells.lymphocytes produce antibodies for killing pathogens. / for blood clotting

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 invasionof 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 toedema.

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. Byneutrophil; 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 memoryare 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.