The Blood Cell,

Immunity

&

Blood Coagulation

Prepared by: Sayyed Nilofer

Introduction Introduction

• Blood is liquid connective tissue.

• Contains extracellular matrix, called blood plasma and various suspended

cells and dissolved substances.

• Contains 7% body weight.

• Blood helps to communicate between body cells and external environment.

• The volume and concentration of most of the constituents of blood is

maintained by appropriate control systems and homeostasis is maintained.

Functions of Blood

A) Transportation:

•Carries oxygen from lungs to tissues; carbon dioxide.

•Carries nutrients from GIT to body cells.

•Carries hormones from endocrine glands

•Transport heat from most active to less active tissue

•Transport of waste products to kidney

•Transport of antibodies to site of infection.

B) Regulation:

•The blood is always in motion, and thus helps to maintain the homeostasis of body

fluids.

•Regulate the pH of body fluids.

•Adjust the body temperature.

•Maintain the correct water content of the cells.

C) Protection:

•In case on injury the blood coagulates and prevents blood loss.’

•WBC protect against diseases by phagocytosis.

Composition of Blood Composition of Blood

• More dense and viscous than water.

• Slightly sticky in nature.

• Temperature of blood is 30 .℃

• Alkaline pH ranging from 7.45 – 7.55

• 5-6 litres in average male and

• 4-5 litres in average female.

• Two components:

Blood plasma

Blood cells

Blood PlasmaBlood Plasma

• Plasma is straw coloured transparent fluid.

• Constitutes about 55% of blood volume.

• 91.5% water and 8.5% solute i.e. dissolved substance

1. Plasma proteins

2. Inorganic salts or mineral salts.

3. Nutrient materials

4. Organic waste products

5. Hormones

6. Antibodies

7. Gases

Plasma ProteinsPlasma Proteins

• Hepatocytes synthesize plasma proteins except gamma globulin.

• The main plasma proteins are:

i. Albumin (54%)

ii. Globulin (38%)

iii. Fibrinogen (7%)

iv. Others (regulatory enzymes, proenzymes and hormones)

i] ALBUMIN:

•Globular protein.

•Encoded by ALB gene.

•It is unglycosylated protein with mol. Wt. 65000 Daltons.

•Present in blood as negatively charged.

Functions:

1.Plays important role in maintenance of osmotic pressure of blood. (25mm Hg)

2.Act as carrier protein for steroids, fatty acids and thyroid hormones.

3.Stabilize extracellular fluid volume.

ii] GLOBULIN:

•Globular protein.

•Higher molecular weight and solubility than albumin

•Produced in liver and immune system.

•Four types: a) Alpha 1 globulin b) Alpha 2 globulin (92 kDa)

c) beta globulin d) gamma globulin (120 kDa)

Functions:

1.Alpha and beta globulin help in transfer of substances i.e. act as transporter.

2.Act as substrate for enzyme in some metabolic reaction.

3.Gamma globulin are immunoglobulin and play role in immunity.

iii] FIBRINOGEN:

•Soluble, glycoprotein with molecular weight of 340 kDa.

•Synthesized in liver by hepatocytes.

•It plays important role in coagulation of blood.

2. Inorganic salts or minerals:

•Salts like sodium chloride, sodium bicarbonate, potassium, magnesium, iron,

phosphorus, iron, calcium, iodine, etc.

•These salts maintain the pH of blood (7.35-7.45)

•Involved in contraction of muscles.

3. Nutrient materials:

•Glucose, amino acids, fatty acids, glycerol and vitamins.

•Provide energy, heat and components for repair and replacement of tissues.

4. Organic waste products:

•Urea, uric acid, creatinine are formed in liver.

•Blood carries them to kidney for excretion.

•Carbon dioxide present in plasma is transported to lungs for excretion.

5. Hormones:

•Synthesized by endocrine glands.

•Blood transports hormones to target organ.

•E.g. growth hormone, insulin, etc.

6. Antibodies:

•These are protective substances produced by blood cells in response to foreign

substance or antigen.

7. Gases:

•Oxygen, carbon dioxide and nitrogen are the important gases that are transported all

over the body.

Erythrocytes or RBCs

• RBCs are biconcave discs.

• Plasma membrane of RBCs is strong and flexible.

• Their flexibility allows them to squeeze through narrow capillaries without

rupturing.

• Plasma membrane consist of glycolipids i.e. antigen.

• The presence or absence of antigen is responsible for blood groups.

• Nucleus absent.

• Cytoplasm contains hemoglobin molecule.

• Each RBC contains 280 million Hb molecules.

Life span and functions of RBCsLife span and functions of RBCs

• Erythrocytes are produced in red bone marrow, which is present in the end of long

bones and in flat and irregular bones.

• Life span in circulation is 120 days.

• The process of development of RBC from pluripotent stem cells takes about 7

days and is called erythropoiesis.

• The stem cells in red bone marrow called hemocytoblast give rise to all elements

of blood.

• Hemocytoblast RBCs (2 million/ sec)

• Vitamin B12 and folic acid are required for RBC synthesis.

2 days

• The bone marrow produce erythrocyte at the rate at which they are destroyed.

• The stimulus to increase erythropoiesis is hypoxia i.e. deficient supply of oxygen.

• This is when:

1. Oxygen carrying power of blood is reduced e.g. hemorrhage.

2. Oxygen tension in air is reduced.

Hemolysis:

• Breakdown of RBC is called hemolysis.

• Carried out by phagocytic reticuloendothelial cells.

• Main site is spleen, bone marrow and liver.

• Iron released is retained in the body and reused by bone marrow to form new Hb

molecule.

Hemolysis

Types of WBC

II] Agranular leucocytes:

1.Lymphocytes:

•Large, round or slightly indented and stain darkly.

•Diameter: S- 6-9μm L- 10-14μm

•Two types: a) T-lymphocytes b) B-lymphocytes

•Normal range: 20-50%

•Function: provide specific protection.

activate activate

Thymosin in thymus gland Bone marrow & lymphoid tissue

2. Monocyte:

•Large mononuclear cells.

•Size: 12-20 μm

•Nucleus: kidney shaped or horse shoe.

•Cytoplasm: blue-gray

•Normal number: 2-10%

•No. increases in conditions of viral infections or fungal infections.

•Count decreases in bone marrow depression.

•Function:

-Protection in the body by phagocytosis

-T and B cells produce interleukin. (endogenous pyrogen)

-Estimation of WBC by hemocytometer.

Non-specific Defense System

• The human being have the innate ability to prevent the entry and establishment

of microorganism in the body by several mechanism.

• These mechanism provide immediate protection against wide variety of

pathogens.

• Non specific mechanism do not produce specific response to specific invader.

i) First line defense: Skin and mucus membrane

ii) Second line defense: antimicrobial protein, natural killer cells, phagocytosis,

fever, inflammation.

ii) Second line defense:

1.Antimicrobial proteins:

Present in blood and interstitial fluid

Interferons: produced from lymphocyte, macrophages and fibroblast infected with

virus.

Neighboring cells.

Synthesis of antiviral protein

Protection from viral infection

Complement system: Inactive protein present in blood plasma and plasma membrane

of cells.

Cytolysis and promote phagocytosis.

Diffuse

2. Natural Killer Cell:

5-10% lymphocytes are NK.

Location: Spleen. Lymph nodes and bone marrow.

Kill infected and tumor cells.

Attack any body cells that display abnormal plasma membrane.

3. Inflammation:

Redness, heat, swelling and pain.

Response occurs in 3 stages;

i.Vasodilation and increase permeability of blood vessels

ii.Emigration of phagocytes

iii.Tissue repair.

Specific Defense System

• The ability of body to fight against the specific invader such as bacteria, toxin,

viruses and foreign substances.

• Any substance recognized by the body as foreign substance and initiate

immunity response is called as antigen.

• Antigen has ability to provoke immunity response called immunogenicity.

• Types of immune responses:

1. Cell mediated immune response

2. Antibody mediated immune response

ALLERGYALLERGY

A number of conditions caused by hypersensitivity of the immune system to

something in the environment that usually causes little or no problem in most

people.

Four types:

1. Type I (Anaphylactic)

2. Type II (Cytotoxic)

3. Type III (Immune complex)

4. Type IV (Cell mediated)

Thrombocytes/ Platelets

• Disc-shaped

• Diameter 2-5μm

• Non-nucleated but contain many vesicles

• Normal count: 1,50,000 to 4,00,000/μl of blood.

• Produced in bone marrow from hemocytoblast.

• Life span: 8-11 days

• Production is influenced by hormone thrombopoietin.

• Granules promote blood clotting.

Blood GroupsBlood Groups

Rh blood groupRh blood group

• The antigen for this blood type was first discovered in the blood of rhesus

monkey.

Blood TransfusionBlood Transfusion

• Transfusion is the transfer of whole blood or component into the blood stream or

bone marrow.

• To improve immunity, increase blood volume and to alleviate anemia.

• If blood groups are not compatible to blood leads to clumping of the RBCs.

Tissue & Organ TransplantationTissue & Organ Transplantation

• The injured or diseased organ such as heart, liver, kidney, lungs, pancreas are

replaced with an organ donated by another individual.

• The immune system of recipient recognizes the proteins present on the

transplanted organ as foreign and initiate cell mediated and antibody mediated

response against the transplanted organ.

• This reaction is known as Graft Rejection.

• The tissue compatibility b/w donor and recipient decreases the probability of

transplant rejection, which depends on histocompatibility antigens present on

transplanted organ.

• Before transplantation Tissue Typing Test is done.

• Technique:

Mixed leucocyte reaction.

Micro-cytotoxicity assay

• To reduce risk of graft rejection immunosuppressant drugs are given.

E.g.: cyclosporin.

• These drug will inhibit only T cells but B cells are not inhibited.

• HLA- Human Leukocyte Antigen

• MHC- Major Histocompatibility Complex

HISTOCOMPATIBILITY: Quality of tissues being compatible.

This term is used in transplant to describe the ability of a donor tissue or organ to be

accepted by the recipient.

• MHC is group of gene in animals.

• In human MHC is called HLA. These are protein present on the surface of WBC

and other tissue.

• The best donor is one whose HLA matches very closely to the patient.

• HLA markers are inherited from parents.

ClassificationClassification

• Disorder in which hemoglobin count in blood decreases more than normal.

Anemia

Impaired erythrocyte production Increased erythrocyte loss

Iron deficiency

Megaloblastic anemia

Hypoplastic anemia

Hemolytic anemia

Normocytic anemia

I] Iron deficiency anemia

•Normal daily requirement of iron in men is 1-2mg, and women 3mg.

•The anemia is regarded as severe when Hb level is below 9g/dl blood.

•In this type RBCs are microcytic and hypochromic because of low Hb.

Normal requirement, deficient intake:

•Deficiency increases if the daily diet is restricted

Poorly planned vegetarian diets

Weight reducing diets

Babies dependent on milk.

High requirement:

•Occurs during pregnancy, when iron requirement are increased for fetal growth and to

support additional load on mothers cardiovascular system.

•Chronic blood loss i.e. peptic ulcers, heavy menstrual bleeding, hemorrhoids.

Malabsorption:

• Iron absorption is increased during hemorrhage.

• Abnormalities of stomach, duodenum or jejunum.

• Iron absorption is dependent on acid environment of stomach, increase in gastric pH

may reduce it.

• Loss of surface area for absorption. E.g.: after surgical removal.

II] Megaloblastic anemia

•Maturation of RBCs is impaired when deficiency of vitamin B12 or folic acid occurs.

•Abnormal large erythrocytes are found in blood (megaloblast).

•During normal erythropoiesis several cell division occur and daughter cells are smaller than

parent cell at each stage since there is not much time for cell enlargement.

•But deficiency of Vitamin B12 or folic acid rate of DNA & RNA production is reduced,

delaying cell division.

•The cells grow larger than normal b/w cell division.

•Circulating cells are immature, some are nucleated, large.

•Hb content is normal or raised.

•Cells are fragile.

•Life span reduced to 40 – 50 days.

•Depressed production and early lysis cause anemia.

Vitamin B12 deficiency anemia:

1. Pernicious Anemia:

• Occurs often in female than males, usually b/w 45-65 years of age.

• Autoimmune disease in which antibodies destroy intrinsic factor and parietal cells

in stomach.

2. Dietary deficiency of B12:

• Rare, except in true vegans, i.e. when no animal products are included in diet.

Gastrectomy – leaves few cells available to produce IF after partial resection of

stomach.

Chronic gastritis – these damage the gastric mucosa including parietal cells.

Malabsorption – if terminal ileum is removed or inflamed (Crohn’s disease)

3. Folic Acid Deficiency Anemia:

•Deficiency in bone marrow causes megaloblastic anemia identical to that seen in B12

deficiency but not associated with neurological damage.

•It occur due to;

Dietary deficiency, e.g. in infants delay in establishing a mixed diet, in alcoholism, in

pregnancy when requirement is raised.

Malabsorption from jejunum, e.g. coeliac disease, anticonvulsant drugs.

Interference with folate metabolism e.g. cytotoxic and anticonvulsant drugs.

III] Hypoplastic Anemia & Aplastic Anemia

•Bone marrow function is reduced in hypoplastic anemia and absent in aplastic anemia.

•Causes leucopenia, diminished RBC number and thrombocytopenia.

•When all 3 cell types are low the condition called pancytopenia and accompanied by

anemia with less immunity and tendency to bleed.

•Causes include:

Drugs: e.g. cytotoxic drugs, anti-inflammatory drugs, anticonvulsant drugs, some

antibiotics.

Ionising radiation

Some chemicals, e.g.: benzene and its derivatives.

Viral disease, hepatitis.

Invasion of bone marrow.

B] Increased erythrocyte loss

I] Hemolytic anemia

•Occur when red cells are destroyed while in circulation or the cells are removed prematurely

because cells are abnormal.

1. Congenital hemolytic anemia:

•Genetic abnormality leads to the synthesis of abnormal Hb and increased red cell membrane

friability, reducing their oxygen-carrying capacity and life span.

a) Sickle cell anemia:

•Abnormal hemoglobin molecule become misshapen when deoxygenated, making RBC sickle

shaped.

•High proportion of abnormal molecules, sickling is permanent.

•Lifespan of cells is reduced.

•Sickle cells do not move smoothly through the small blood vessels.

•This increases the viscosity of blood, reducing the rate of blood flow leading to intravascular

clotting.

Complication:

• Pregnancy, infection and dehydration predispose development of “Sickle crises”

due to intravascular clotting causing severe pain in long bones. Chest or abdomen.

• Formation of gall stone and inflammation of gall bladder.

b) Thalassemia

• Severe cases death in infants or young children.

• Common in Mediterranean countries.

Reduced globin synthesis

Reduced Hb

Increased friability of cell membrane

Early hemolysis

c) Hemolytic disease of new born

II] Normocytic Anemia

•The cells are normal but the number is reduced, and the proportion of reticulocyte in

the blood may be increased as the body tries to restore erythrocyte number to normal.

•This occurs:

Chronic inflammation

Following severe hemorrhage

Hemolytic disease.

POLYCYTHEMIAPOLYCYTHEMIA

• Definition: Abnormal large number of erythrocytes in blood.

- This increases blood viscosity.

- Slows the rate of blood flow

- Increases intravascular clotting, ischemia and infraction.

• This occurs when the RBC count is normal but the blood volume is reduced by fluid

loss, e.g. excessive serum exudate from excessive burns.

• Prolong hypoxia stimulated erythropoiesis.

• Cigarette smoking

• Pulmonary disease

• Bone marrow cancer.