Blood Tahmina Yasmin Lecturer North South University

BloodBlood

Tahmina Yasmin

Lecturer

North South University

Definition

Blood is a specialized fluid connective tissue consisting of some cells suspended in a liquid intercellular substance known as plasma.

Major functions of blood• Transport of respiratory gases

• Transport of nutrients

• Act as vehicle

• Regulation of body temperature

• Regulation of water and electrolyte balance

• Maintenance of acid-base balance

• Excretory function

• Defensive action

Composition of blood

Blood is composed of mainly two parts:

• Plasma

• Blood cells

PLASMA

• Plasma contains- 1)Water (92%) 2)Solid(8%) i) Inorganic constituents• E.g. Na+, K+, Ca++, Mg++ etc.• ii) Organic constituents• a) Non protein nitrogenous substance e.g.

urea, uric acid.• b) Fats e.g. lipid, cholesterol• c) Protein e.g. albumin, globulin (7%)• d) Carbohydrate e.g. glucose, sucrose• e) Coloring materials e.g. bilirubin

Function of plasma protein• It helps in exchange of fluid between blood and

tissue spaces.

• It is essential for the coagulation of blood.

• It acts as buffer and maintains acid-base balance.

• It helps in carriage of CO2 by forming carboamino protein.

• Gamma-globulin is antibody in nature and performed defensive action against infection.

• It helps in transport of lipid, hormone, drugs etc.

• Erythrocyte/RBC• Leukocyte/WBC• Thrombocyte/Platelet

BLOOD CELLSBLOOD CELLS

Red blood cell (R.B.C) or Erythrocytes

Characteristics The mature human R.B.C is -• A circular, biconcave and non-

nucleated (i.e. without any nucleus) cell.

• Soft and flexible and readily be squeezed through narrow capillaries.

• Internally composed of a framework which is built of many lipids and proteins and gap within the frame work is filled with hemoglobin.

• The membrane of the R.B.C is selectively permeable.

• Composition

• i) Water : 65%

• ii) Solid : 35%a) Hemoglobin -33%

b)Others e.g. protein, lipid, fat -2%

Erythropoesis• Formation of red blood cells (R.B.C or

erythrocytes) is known as erythropoesis.

• Red blood cells originate from the embryonic tissue (mesoderm) and the main sites of erythropoesis are bone marrow and spleen.

• The main factor influencing the red blood cells production is the oxygen content of the arterial blood.

• Decrease in oxygen content in the arterial blood decreases oxygen tension in the tissue, which is known as hypoxia.

• Hypoxic state leads to the production of glyprotein called erythropoietin or haemopoetin, which is also known as erythrocyte stimulating factor (ESF).

• This factor is released from the renal tissue ( Juxtra glomerular cells or JG cells) and stimulates erythropoesis or red blood cell production from the bone marrow.

• The erythropoetin acts on the stem cells of bone marrow and converts it into haemocytoblasts which in turn converts into erythrocytes.

• Factors essential for erythropoesis• Protein: Food rich in first class protein is very necessary. These

proteins are intended to supply the essential amino acids for the synthesis of globin portion of hemoglobin.

• Hypoxia: Low oxygen tension or level in the arterial blood provides

a physiological stimulus for erythropoesis (red cell production) through the action of erythropoetin.

• Other maturation factors: Vitamin B12 (cyanocobalamin) and folic acid, some

metals like Cu, Mn, Co, Ca, vitamin C, thyroxin hormone.

Fate of red blood cells• After an average time period of 120 days, special

cells known as reticulo-endothelial cells (R.E Cells) of liver and spleen engulf (swallow) the senile (old) red blood cells and break them.

• Hemoglobin is released and iron is freed from them . • The freed iron is stored in the body as ferritin and

haemosiderin, which help in the formation of new hemoglobin later on.

• The rest of the haem molecule is converted into some pigments such as bilirubin (yellow in color) and biliverdin (greenish in color).

Major functions of RBC• Respiratory functions: Red cells carry oxygen ( from

lungs to the tissue) and carbon dioxides (from tissue to the lungs).

• Acid-base balance: Hemoglobin (and also the plasma protein) have got the buffering action and thus contribute to the acid base balance of plasma.

• Viscosity of blood: RBC helps to maintain the viscosity of blood. If RBC is increased in plasma, viscosity of blood will increase.

• Formation of pigments: Various pigments like bilirubin, biliverdin are derived from hemoglobin.

• White blood cells/Corpuscles (W.B.C) or LeukocytesCharacteristics:

The mature human W.B.C has got the following characteristics:

• It lacks hemoglobin but contains nucleus.

• They are much less in number.

• Their average total number is 6000 to 8000 per cubic mm.

• They are amoeboid (i.e. amoeba like)

• Their life span is shorter (few days to month)

• These are produced from the lymphatic system.

Leukocytes (Greek: “White Hollows”)

• All WBCs (leukocytes) have a nucleus and no hemoglobin.• Protect body against microorganisms and remove dead cells

and debris.• Granular or agranular classification based on presence of

cytoplasmic granules made visible by staining.• Types & Functions• Granulocytes

– Neutrophils: Small phagocytic cells– Eosinophils: Reduce inflammation– Basophils: Release histamine and increase inflammatory

response• Agranulocytes

– Lymphocytes: Immunity– Monocytes: Become macrophages

NeutrophilsFeatures• Neutrophils are the most abundant leukocytes in

blood. Nuclei contains 2 to 5 lobes connected by thin strands.

• Neutrophils are Filled with granules (e.g. Lysosomes)

Functions• Give fastest response of all WBC to bacteria and

parasites.• Very active migration

– Sensitive to chemotactic factors which attract them to infection site

• Direct actions against bacteria– release lysozymes which destroy/digest bacteria– release defensin proteins that act like antibiotics– release strong oxidants (bleach-like, strong

chemicals ) that destroy bacteria

EosinophilsFeaturesGenerally larger than neutrophils• Stain orange-pink with eosin

– Contain abundant basic protein• Nucleus with 2 or 3 lobes connected by a thin strand

Functions• Leave capillaries to enter tissue fluid• Release histaminase

– slows down inflammation caused by basophils• Attack parasitic worms• Phagocytize antibody-antigen complexes.

BasophilFeatures• Least common leukocyte• Stains with basic dyes• Precursor of mast cells in tissues.

Functions• Involved in inflammatory and allergy

reactions.• Leave capillaries & enter connective tissue as

mast cells.• Release heparin, histamine & serotonin

– heighten the inflammatory response and account for hypersensitivity (allergic) reaction.

– Heparin is a potent anti-coagulant that does not allow clotting within vessels.

Monocyte (Agranulocyte)Features• Nucleus is kidney or horse-shoe shaped• Largest WBC in circulating blood

– does not remain in blood long before migrating to the tissues

– differentiate into macrophages. • Fixed groups are found in specific tissues (alveolar

macrophages in lungs, kupffer cells in liver. • Wandering group gathers at sites of infection

Functions• Take longer to get to site of infection, but arrive in larger

numbers• Destroy microbes and clean up dead tissue following an

infection

Lymphocyte (Agranulocyte)Features• Dark, oval to round nucleus• Cytoplasm sky blue in color• 20 to 25% of circulating WBCs

Functions• B cells

– destroy bacteria and their toxins– turn into plasma cells that produces antibodies

• T cells– attack viruses, fungi, transplanted organs, cancer cells

• Natural killer cells– attack many different microbes & some tumor cells– destroy foreign invaders by direct attack

Differential WBC Count (DC)• Detection of changes in numbers of circulating

WBCs (percentages of each type)– indicates infection, poisoning, leukemia,

chemotherapy, parasites or allergic reaction

• Normal WBC counts– TC (Total count): 5,000-10,000 / L– DC (Differential count)

• neutrophils 60-70% (up if bacterial infection)• lymphocyte 20-25% (up if viral infection)• monocytes 3 -- 8 % (up if fungal/viral infection)• eosinophil 2 -- 4 % (up if parasite or allergy reaction)• basophil <1% (up if allergy reaction or hypothyroid)

• Major functions• Defensive action:

– Phagocytosis: The neutrophils and monocytes engulf foreign particles and microorganism.

– Antibody formation: Lymphocytes produce antibodies (mainly gamma globulin) and play an important role in defensive mechanism of the body.

• Secretion of heparin: The basophils secret heparin, which helps in the prevention of intravascular clot.

• Manufacture of trephones: Leukocytes produce some special protein like substance known as “trephones” which have great influence on nutrition, growth and tissue repair .

Platelets (Thrombocytes)• Disc-shape cell fragment with no nucleus• Platelets are the cell fragments pinched off from megakaryocytes in red

bone marrow• Platelets are important in preventing blood loss

– Platelet plugs– Promoting formation and contraction of clots

Platelets--Life History• Platelets form in bone marrow by following steps:

– myeloid stem cells eventually become megakaryocytes whose cell fragments form platelets.

• Short life span (5 to 9 days in bloodstream)– They are formed in bone marrow.– They remain few days in circulating blood.– Aged ones are removed by fixed macrophages in liver and spleen.

– Normal count: 2-4 lacs /cubic mm of blood.

• Major functions

• Blood coagulation: When blood is shed, the platelets disintegrate and liberate thromboplastin, which activates prothrombin into thrombin.

• Repair of capillary endothelium: While in the circulation, the platelets adhere to the damaged cell lining of the capillaries and thus bring about a speedy repair.

HEMOGLOBIN

• Hemoglobin is a conjugated protein. It is the red pigment inside the red blood cells. It consists of two parts-

• Globin – 96%• Haem – 4%.• Normal count:• In male : 14 – 18g/100ml of blood.• In female : 12 – 15.5g/100ml of blood.

• Function of hemoglobin

• It is essential for transport of O2 from lungs to the tissue and CO2 from tissue to the lungs.

• It is an important blood buffer and helps to maintain PH of the blood.

• Various pigments like bilirubin, biliverdin etc are derived from hemoglobin.

• It reserves iron and protein.

Structure of hemoglobin

Hemoglobin

Globin

Haem

α- Chain

β- Chain

Fe++

porphyrin ix

• Haem• From structural point of view, haem

is a metalloporphyrin type of compound consisting of four pyrrole structures joined with one another with a ferrous iron (Fe++) in the center.

• Porphyrins are complex heterocyclic compound that contain a ring structure, which is formed by four pyrrole rings by methine (=CH-) bridges.

• The porphyrin ring present in haem molecule is known as protoporphyrin ix.

• Globin• There are two pairs of globin chain, i.e. two α

chain and two β chain. Two subunits of haem combine with two α chains and other subunits of haem combines with two β chains. Each α chain contains 141 amino acids. Each β chain contains 146 amino acids.

• Iron of hemoglobin• Iron in haem is in ferrous (Fe++) form. Iron is

attached to the N of each pyrrole ring.

HemostasisHemostasis• Hemostasis is stoppage of bleeding in a quick & localized fashion when

blood vessels are damaged.

• Main goal of Hemostasis is to prevent hemorrhage (hemorrhage is loss of a large amount of blood)

Opposite of hemorrhage Opposite of hemorrhage stops bleeding stops bleeding

Too little hemostasis Too little hemostasis too much bleeding too much bleeding

Too much hemostasis Too much hemostasis thrombi / emboli thrombi / emboli

Three major steps:Three major steps:

1.1. VasoconstrictionVasoconstriction

2.2. Platelet plugPlatelet plug Temporarily blocks the hole Temporarily blocks the hole

1.1. Platelet-derived cytokines further the processPlatelet-derived cytokines further the process

3.3. Coagulation cascadeCoagulation cascade (= clot formation seals hole until tissues (= clot formation seals hole until tissues repaired)repaired)

1.1. Two pathways: Extrinsic and IntrinsicTwo pathways: Extrinsic and Intrinsic

4.4. After vessel repair, plasmin dissolves the clotAfter vessel repair, plasmin dissolves the clot

Steps of Hemostasis

1)Vascular Spasm

• Damage to blood vessel stimulates pain receptors• It causes reflex contraction of smooth muscle of

small blood vessels.• Vascular Spasm can reduce blood loss for several

hours until other mechanisms can take over.• Vascular Spasm is effective only for small blood

vessel or arteriole.

• Platelets store a lot of chemicals in granules needed for platelet plug formation

–ADP, Ca+2, serotonin, fibrin-stabilizing factor, & enzymes that produce thromboxane A2

• There are three steps in the process of Platelet plug formation– (i) platelet adhesion – (ii) platelet release reaction – (iii) platelet aggregation

2) Platelet plug formation

Platelet plug formation: Stepsi. Platelet Adhesion• Platelets stick to exposed collagen underlying damaged

endothelial cells in vessel wall

ii. Platelet Release Reaction• Platelets activated by adhesion• Extend projections to make contact with each other • Release thromboxane A2, serotonin & ADP activating other

platelets• Serotonin & thromboxane A2 are vasoconstrictors decreasing

blood flow through the injured vessel. ADP causes stickiness

iii. Platelet Aggregation• Activated platelets stick together and activate new platelets to

form a mass called a platelet plug• Plug reinforced by fibrin threads formed during clotting process

Platelet Plug Formation

Von Willebrand Factor : A large blood protein that plays an important role in platelet gathering at the site of a wound

3)Blood ClottingBlood clotting – It is a process in which liquid blood is

changed into a semisolid mass (a blood clot).• Clotting is activated by tissue damage or when blood

come in• Clotting is a cascade of reactions in which each clotting

factor activates the next in a fixed sequence resulting in the formation of fibrin threads

Blood Coagulation TestsBleeding time : (Normal Range: 1-6 minutes)Clotting time : (Normal Range: 6-10 minutes)

Blood Coagulation

• Coagulation is a complex process by which blood forms clots.

• It is an important part of hemostasis (the cessation of blood loss from a damaged vessel), wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel

• So A blood clot consists of

-a plug of platelets

-enmeshed in a network of insoluble fibrin molecules.

Overview of the Clotting Cascade Extrinsic Pathway: -Chemical outside the blood triggers blood coagulation.-This pathway is initiated by damaged tissues. -Damaged tissues leak tissue factor (thromboplastin) into bloodstream.• Prothrombinase forms in seconds

Intrinsic Pathway: Activation occurs when– endothelium is damaged & platelets come in contact with collagen of

blood vessel wall– Triggered by Hageman factor (found inside blood)– platelets damaged & release phospholipids

• Requires several minutes for reaction to occur

Final common pathway• Prothrombinase is formed by either the intrinsic or extrinsic pathway• Final common pathway produces fibrin threads

– prothrombinase & Ca+2 convert prothrombin into thrombin– thrombin converts fibrinogen into fibrin threads– Fibrin threads trap blood cells and proteins

• Clot retraction follows minutes after cascade

Clotting Factors• Factor I = Fibrinogen • Factor II = Prothrombin • Factor III = Tissue factor • Factor IV = Calcium • Factor V = Labile factor • Factor VI - Does not exist as it was named initially but later on

discovered not to play a part in blood coagulation. • Factor VII = Stable factor • Factor VIII = Antihemophilic factor A • Factor IX = Antihemophilic factor B or Christmas factor (named after

the first patient in whom the factor deficiency was documented) • Factor X = Stuart Prower factor • Factor XI = Antihemophilic factor C • Factor XII = Hageman factor • Factor XIII = Fibrin stabilising factor

** Why blood does not clot inside the blood vessel?

• Blood does not clot inside the blood vessel because-– Endothelium of blood vessels are quite

smooth and non water wettable. A rough and water wettable substance is required for clotting.

– Speed of the blood flow is optimum to prevent coagulation.

– Presence of natural anticoagulants like heparin, antithrombin, etc.

Clotting disorders

1)Afibrinigenaemia or fibrinogenopenia:

Rare congenital disease characterized by absence of fibrinogen in blood.

2)Hemophilia:

This is a genetic disease characterized by unstoppable hemorrhage. This happens due to absence of a particular clotting factor – VIII or AHG (Anti-Haemophillic Globulin).

3) Lack of prothrombin or vitamin K: • Vitamin K helps in the formation of prothrombin

in liver. • This vitamin is absorbed from the small

intestine in presence of bile salts. • In the liver disease like liver cirrhosis and other

malignant disease, there is impaired prothrombin synthesis in the liver.

• Again in some cases, prothrombin synthesis may be hindered because of inadequate presence of vitamin K (For example, in obstructive jaundice, there is lack of bile salts and for this reason, vitamin K is not properly absorbed).

• Thrombosis:• Thrombus is a clot formed within the unbroken blood

vessel. • It is formed- - on rough inner lining of BV. For example, cholesterol

can abnormally deposit over the vascular endothelium and turns it narrow, water wettable and rough and thus results clotting.

-if blood flows too slowly (stasis) allowing clotting factors to build up locally & cause coagulation

-Due to damage or injury of the vascular endothelium.• This phenomenon is known as atherosclerosis and this

gradually lead to coronary thrombosis and other fatal disorders.

• Embolism:• In some times, the thrombus or intravascular clot can get dislodged

and float via blood circulation.

• This mobile thrombus or clot is known as embolus. The disorder then can be called as embolism.

• Embolism can be classified as whether it enters the circulation in arteries or veins.

• Arterial embolism is a sudden interruption of blood flow to an organ or body part due to an embolus adhering to the wall of an artery and blocks the flow of blood.

• A venous embolism is a blood clot that forms within a vein. Assuming a normal circulation, a embolus formed in a systemic vein will always impact in the lungs (pulmonary embolus), after passing through the right side of the heart.

• Purpura:• Purpura (from Latin: purpura

, meaning "purple") is the appearance of red or purple discolorations on the skin that do not blanch on applying pressure.

• They are caused by bleeding underneath the skin.

• It is due to platelet deficiency.

• ANEMIA:• Anemia is a condition characterized by abnormally

low levels of healthy red blood cell or hemoglobin.• Causes of Anemia:

– Excessive blood loss due to acute or chronic hemorrhage

– Reduced production of RBC due to lack of some factors which are necessary for RBC production

– Excessive blood cell destruction in comparison to the production of blood cells

– Destruction of bone marrow– Infections– Certain diseases– Poor nutrition

• Symptoms: Most common symptom of anemia are

a result of decrease of oxygen on the cells i.e. hypoxia.

• The following are the most common symptoms of anemia-

• Headache• Irritability• Abnormal paleness or lack of color of

the skin.

• Increased heart rate • Breathlessness• Dizziness or vertigo, Especially when

standing• Lack of energy• Sore or swollen tongue(glossitis)• Jaundice• Enlarged spleen or liver(Splenomegaly

or hepatomegaly)

Symptoms(Cont.)

• TREATMENT OF ANEMIA:

• 1) Treatment of the causative diseases

• 2) Vitamin and mineral supplements

• 3) Change in diet

• 4) Medication

• 5) Blood transfusion

• 6) Bone marrow transplant

• 7) Surgery

• 8) Antibiotic therapy

• TYPES OF ANEMIA:• Iron deficiency anemia• Megaloblastic anemia- a) Folic acid deficiency anemia

b) Vitamin B12 deficiency anemia

• Hemolytic anemia - Sickle cell anemia• Thalassemia• Aplastic anemia• Chronic anemia

• 1) Iron deficiency anemia:

• Iron deficiency anemia is the most common form anemia in the world. If the supply of iron to the bone marrow is insufficient for the requirement of hemoglobin synthesis, iron deficiency anemia occurs.

• CAUSES OF IRON DEFICIECY ANEMIA:• Iron deficiency anemia may be caused by the

following:• 1) Diets low in iron: • Iron is obtained from foods in our diet; however,

only 1 mg of iron is absorbed for every 10 to 20 mg of iron ingested. A person unable to have a balanced iron rich diet may suffer from some degree of iron deficiency anemia.

• 2) Body changes:• An increased iron requirement and increased

red blood cell production is required when the body is going through changes like child growth and adolescence or during pregnancy and lactation.

CAUSES OF IRON DEFICIECY ANEMIA(cont.)

• 3) GI abnormalities:• Malabsorption of iron is common after some

forms of gastrointestinal surgeries(Most of the iron taken in by foods is absorbed in the upper small intestine) Any abnormalities in the gastrointestinal tract could alter iron absorption and result in iron deficiency anemia.

• 4) Blood loss: • Loss of blood can cause a decrease in iron and

result in iron deficiency anemia. Sources of blood loss may include GI bleeding, menstrual bleeding or injury.

• 2) Megaloblastic anemia Megaloblastic anemia is an anemia (of macrocytic

classification) that results from inhibition of DNA synthesis in red blood cell production.

The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically a deficiency of vitamin B12 folic acid and/or intrinsic factor .

Loss of any of these can lead causes abnormal and diminished DNA and, consequently, failure of nuclear maturation and cell division

• 2) Megaloblastic anemia • The erythroblastic cells of the bone marrow, in addition to failing to

proliferate rapidly, produce mainly larger than normal red cells called macrocytes, and the cell itself has a flimsy membrane and is often irregular, large, and oval instead of the usual biconcave disc

• As a result red cell continue to grow without division/or little division, into large, odd-shaped cells called megaloblasts.

These poorly formed cells, after entering the circulating blood, are capable of carrying oxygen normally, but their fragility causes them to have a short life, one half to one third normal.

• Therefore, it is said that deficiency of either vitamin B12 or folic acid causes maturation failure in the process of erythropoiesis.

• a) Folic acid deficiency anemia• Folic acid deficiency anemia is the most

common type of megaloblastic anemia in which RBC are bigger than normal.

• Causes: i) It is caused by a deficiency of folic acid.

• ii) It is sometimes due to inability to absorb enough folic acid from food

• Smoking raises the risk of developing the condition by interfering with the absorption of vitamin C which the body needs to absorb folic acid

• b) Vitamin B12 deficiency anemia:• Vitamin B12 deficiency anemia is one

type of megaloblastic anemia that develops when the body doesn’t absorb enough of this nutrient.

• Large amount of vitamin B12 are stored in the body, so this condition may not become apparent until as much as four years after vitamin B12 absorption stops or slows down.

• Cause:• 1) Lack of intrinsic factors in gastric

secretions (A substance needed to absorb • Vitamin B12 from the GI tract)• 2) Chronic gastritis (Inflammation of

the stomach)• 3) Gastrectomy (Removal of all or

parts of the stomach) • 4) Type -1 Diabetes• 5) Thyroid diseases• 6) Family history of diseases

Symptoms:

–Loss of muscle control

–Loss of sensation in the legs, hands and feet

–Soreness or burning of the tongue

–Weight loss

–Yellow-blue color blindness

• 3) Hemolytic anemia• A hemolytic anemia may be defined as an

anemia resulting from an increase in the rate of red cell destruction.

• This is the result of fragile RBC that rupture as they pass through the capillaries.

• With hemolytic anemia, the no. of RBC that form is normal or in excess of normal.

• However because these cells are extremely fragile, their life span is very short.

• There is two types of hemolytic anemia:

• Intrinsic: The destruction of the red blood cells due to a defect within the RBC itself. Intrinsic hemolytic anemias are often inherited. These conditions produce RBC that does not live as long as normal RBC.

• Extrinsic: Red blood cells are produced healthy but are later destroyed by becoming trapped in the spleen, destroyed by infection or destroyed from drugs that can affect RBC.It is also known as autoimmune hemolytic anemia.

• Causes:• Infections such as hepatitis, cytomegalovirus, and

thyphoid fever• Medications such as penicillin, antimalarial

medication, sulpha medication and acetaminophen etc

• Leukemia• Autoimmune disorder such as rheumatoid arthritis,

Ulcerative colitis etc• Various tumor• gene mutation ex: sickle cell anemia

a)Sickle cell anemia is an inherited blood disorder characterized by defective hemoglobin which is caused by single mutation in the gene of beta globin chain. (the 6th amino acid of the chain being changed from gultamic acid to valine)

• When this hemoglobin is exposed to low concentrations of oxygen, it precipitates into long crystals inside the red blood cell.

• These crystals elongate the cell and give it the appearance of a sickle rather than a biconcave disc

• The precipitated hemoglobin also damages the cell membrane, so that the cells become highly fragile, leading to serious anemia.

• cluster together, then block and clog small blood vessels and thus stop the movement of oxygen-carrying blood.

.

Such patients frequently experience a vicious circle of events called a sickle cell disease “crisis,” in which low oxygen tension in the tissues causes sickling, which leads to ruptured red cells, which causes a further decrease in oxygen tension and still more sickling and red cell destruction.

Once the process starts, it progresses rapidly, eventuating in a serious decrease in red blood cells within a few hours and, often, death

Sickle cells die after about 10 to 20 days, unlike normal hemoglobin cells, which live for up to 120 days. This results in a chronic short supply of RBC as the bone marrow can't make new red blood cells fast enough to replace the dying ones,which causes anemia.

b)Thalassemia

Thalassemia is an inherited disorder. It leads to the decreased production and increased destruction of red blood cells.

In thalassemia the genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin.

This can cause the formation of abnormal hemoglobin molecules, thus causing anemia, the characteristic presenting symptom of the thalassemia.

• i) α- Thalassemia:

• In α- Thalassemia there is an imbalance in the production of the α chain of globin.

• α- Thalassemias result in decreased alpha-globin production, therefore fewer alpha-globin chains are produced, resulting in an excess of ß chains in adults

• ii) β- Thalassemia

• In β - Thalassemia there is an imbalance in the production of the β chain of amino acid.

5) APLASTIC ANEMIA:

• Bone marrow aplasia means lack of functioning bone marrow.

• Aplastic anemia occurs when the bone marrow produces too few of all three types of blood cells (such as RBC, WBC and platelet) due to aplasia of bone marrow.

• A reduced number of red blood cells cause hemoglobin to drop.

• A reduced number of WBC makes the patient susceptible to infection.

• A reduced number of platelets cause the blood not to clot as easily.

• Cause:• Aplastic anemia has multiple causes. Some of these

causes are idiopathic, meaning they occur sporadically for no known reason. Other causes are secondary, resulting from a previous illness or disorder. Acquired causes, however, may include the following:

• History of specific infectious disease such as infectious hepatitis

• History of taking certain medication such as antibiotics and anticonvulsants

• Exposure to certain toxin such as heavy metals• Exposure of radiation• History of an autoimmune disease• Inherited condition

6) Chronic Anemia:

• Cancer, chronic infection or inflammation of kidney and liver disease often cause chronic anemia.

Polycythemia Polycythemia (also known as polycythaemia or erythrocytosis) is a

disease state in which the proportion of blood volume that is occupied by red blood cells increases.

Secondary Polycythemia.

Whenever the tissues become hypoxic because of too little oxygen in the breathed air, such as at high altitudes, or because of failure of oxygen delivery to the tissues, such as in cardiac failure, the blood-forming organs automatically produce large quantities of extra red blood cells. This condition is called secondary polycythemia, and the red cell count commonly rises to 6 to 7 million/mm3, about 30 per cent above normal.

• A common type of secondary polycythemia, called physiologic polycythemia, occurs in natives who live at altitudes of 14,000 to 17,000 feet, where the atmospheric oxygen is very low.The blood count is generally 6 to 7 million/mm3; this allows these people to perform reasonably high levels of continuous work even in a mysterious atmosphere.

Polycythemia• Polycythemia Vera The pathological condition of polycythemia known as

polycythemia vera, in which the red blood cell count may be 7 to 8 million/mm3 and the hematocrit may be 60 to 70 per cent instead of the normal 40 to 45 per cent..

• Polycythemia vera is caused by a genetic aberration in the hemocytoblastic cells that produce the blood cells.

• The blast cells no longer stop producing red cells when too many cells are already present.This causes excess production of red blood cells.

• It usually causes excess production of white blood cells and platelets as well.

• In polycythemia vera, not only does the hematocrit increase, but the total blood volume also increases, on some occasions to almost twice normal.

• As a result, the entire vascular system becomes intensely engorged. • In addition, many blood capillaries become plugged by the viscous blood;

the viscosity of the blood in polycythemia vera sometimes increases 3 times than normal.

History of Blood Groups and Blood Transfusions

•Experiments with blood transfusions have been carried out for hundreds of years. Many patients have died and it was not until 1901, when the Austrian Karl Landsteiner discovered human blood groups, that blood transfusions became safer.

• He found that mixing blood from two individuals can lead to blood clumping. The clumped RBCs can crack and cause toxic reactions. This can be fatal.

http://nobelprize.org/medicine/educational/landsteiner/readmore.html

• Karl Landsteiner discovered that blood clumping was an immunological reaction which occurs when the receiver of a blood transfusion has antibodies against the donor blood cells.

•Karl Landsteiner's work made it possible to determine blood types and thus paved the way for blood transfusions to be carried out safely. For this discovery he was awarded the Nobel Prize in Physiology or Medicine in 1930.

History of Blood Groups and Blood Transfusions (Cont.)

•The differences in human blood are due to the presence or absence of certain protein molecules called antigens and antibodies.

•The antigens are located on the surface of the RBCs and the antibodies are in the blood plasma.

•Individuals have different types and combinations of these molecules.  

•The blood group you belong to depends on what you have inherited from your parents.

What are the different blood groups?

• There are more than 20 genetically determined blood group systems known today

• The AB0 and Rhesus (Rh) systems are the most important ones used for blood transfusions.

• Not all blood groups are compatible with each other. Mixing incompatible blood groups leads to blood clumping or agglutination, which is dangerous for individuals.

What are the different blood groups?

According to the ABO blood typing system there are four different kinds of blood types: A, B, AB or O (null).

ABO blood grouping system

              Blood group AIf you belong to the blood group A, you have A antigens on the surface of your RBCs and B antibodies in your blood plasma.

              Blood group BIf you belong to the blood group B, you have B antigens on the surface of your RBCs and A antibodies in your blood plasma.

AB0 blood grouping system

              Blood group ABIf you belong to the blood group AB, you have both A and B antigens on the surface of your RBCs and no A or B antibodies at all in your blood plasma.

Blood group OIf you belong to the blood group O (null), you have neither A or B antigens on the surface of your RBCs but you have both A and B antibodies in your blood plasma.

ABO Blood Groups

Well, it gets more complicated here, because there's another antigen to be considered - the Rh antigen.

Some of us have it, some of us don't.

If it is present, the blood is RhD positive, if not it's RhD negative.

So, for example, some people in group A will have it, and will therefore be classed as A+ (or A positive).

While the ones that don't, are A- (or A negative).

And so it goes for groups B, AB and O.

The Rhesus (Rh) System

• Rh antigens are transmembrane proteins with loops exposed at the surface of red blood cells.

• They appear to be used for the transport of carbon dioxide and/or ammonia across the plasma membrane.

• They are named for the rhesus monkey in which they were first discovered.

• RBCs that are "Rh positive" express the antigen designated D.

• 85% of the population is RhD positive, the other 15% of the population is running around with RhD negative blood.

The Rhesus (Rh) System (Cont.)

• A person with Rh- blood can develop Rh antibodies in the blood plasma if he or she receives blood from a person with Rh+ blood, whose Rh antigens can trigger the production of Rh antibodies.

•A person with Rh+ blood can receive blood from a person with Rh- blood without any problems.

People with blood group O are called "universal donors" and people with blood group AB are called "universal receivers."

Blood transfusions – who can receive blood fromwhom?

• AGGLUTINATION PROCESS IN TRANSFISION REACTION:

• For a blood transfusion to be successful, AB0 and Rh blood groups must be compatible between the donor blood and the patient blood.

• If they are not (When bloods are mismatched so that anti-A or anti-B plasma agglutinins are mixed with RBC that contain A or B agglutinogens, respectively),the red blood cells from the donated blood will clump or agglutinate as a result of the agglutinins attaching themselves to the RBC.

• Because of the agglutinins Have 2 binding sites (IgG type) or 10 binding sites (IgM type).A single agglutinins can attach to two or more RBC at the same time, there by causing the cells to be bound together by agglutinin. This causes the cells to clump, which is the process of agglutination

• The agglutinated red cells can clog blood vessels and stop the circulation of the blood to various parts of the body.

• The agglutinated red blood cells also crack and its contents leak out in the body. The red blood cells contain hemoglobin which becomes toxic when outside the cell. This can have fatal consequences for the patient.

• This clumping could lead to death

Agglutination Reaction

If a person with A+ blood receives B+ blood,The B antibodies in the A+ blood (Receiver) attack the foreign red blood cells by binding to them. The B antibodies in the A+ blood (Receiver) bind the antigens in the B+ blood (Donor)and agglutination occurs. This is dangerous because the agglutinated red blood cells break after a while and their contents leak out and become toxic.

Why A person with A+ve blood cannot receive from B+ve donor?

• O negative is universal donor• A universal donor is someone who can donate blood to anyone

else, with a few rare exceptions. People with the O-ve blood type have traditionally been considered universal blood cell donors.

• The antibodies in the receiver’s blood attack the donors antigen (foreign red blood cells) by binding to them.

• But Type O blood produces no antigen but both "anti-A" and "anti-B" antibodies.

• If a person with type A blood received a transfusion with type B blood, the recipient's "anti-B" antibodies would attack the B blood cells.

• However, if the same person received type O blood, the "anti-B" antibodies have no target antigen and thus would not attack the O blood cells. This is also true for B blood type recipients.

• AB is universal Receiver• Blood group AB is a universal receiver because they can

receive blood from any blood group. However, they can only donate blood to other people with blood group AB.

• But Group AB – has both A and B antigens on red cells,but neither A nor B antibody in the plasma.

• Normally the antibodies in the receiver’s blood attack the donors antigen (foreign red blood cells) by binding to them.

• So type AB can receive blood from any group as there is no antibody present in receivers blood to attack donors antigen .

Erythroblastosis Fetalis• Erythroblastosis fetalis, also known as hemolytic disease of the

newborn, is a disease in the fetus or newborn which is characterized by high erythroblast count in fetus.

• It is caused by transplacental transmission of maternal antibody, usually resulting from maternal and fetal blood group incompatibility.

• Rh incompatibility may develop when a woman with Rh-negative blood becomes pregnant by a man with Rh-positive blood and conceives a fetus with Rh-positive blood.

• Red blood cells (RBCs) from the fetus leak across the placenta and enter the woman's circulation throughout pregnancy with the greatest transfer occurring at delivery.

• This transfer stimulates maternal antibody production against the Rh factor, Maternal antibodies against fetal red blood cell antigens pass through the placenta into the fetus, where an excessive destruction of fetal red blood cells occurs.

Erythroblastosis Fetalis

Erythroblastosis Fetalis• The baby becomes anemic and hypoxic .The baby's body tries to

compensate for the anemia by releasing immature red blood cells, called erythroblasts, from the bone marrow.

• The overproduction of erythroblasts can cause the liver and spleen to become enlarged, potentially causing liver damage or a ruptured spleen.

• Since the blood lacks clotting factors, excessive bleeding can be a complication.

• When such hemolysis begins during pregnancy, stillbirth may result. the pregnant woman will generally notice a decrease in fetal movement.Brain damage and death may result if blood transfusions are not performed.

• While there is little danger of damage to the fetus during the first pregnancy, by the second pregnancy sufficient antibodies will have accumulated in the mother’s bloodstream to cause increasing danger of hemolytic disease.

• Why Erythroblastosis Fetalis is fatal for second pregnancy?

Erythroblastosis Fetalis

THANKS

• b) Agranulocyte: Having no granules in cytoplasm and nucleus is nonlobular. They again are divided into two types

i) Lymphocytes

ii) Monocytes

Serum ProteinsProteins make up 6–8% of the blood. They are about equally divided between serum albumin and a great variety of serum globulins. After blood is withdrawn from a vein and allowed to clot, the clot slowly shrinks. As it does so, a clear fluid called serum is squeezed out. Thus:Serum is blood plasma without fibrinogen and other clotting factors.

The most prominent of these and the one that moves closest to the positive electrode is serum albumin.

Serum albumin is made in the liver binds many small molecules for transport through the blood helps maintain the osmotic pressure of the blood.

The other proteins are the various serum globulins. They migrate in the order alpha globulins (e.g., the proteins that transport thyroxine and retinol [vitamin A]) beta globulins (e.g., the iron-transporting protein transferrin) gamma globulins.

Gamma globulins are the least negatively-charged serum proteins. (They are so weakly charged, in fact, that some are swept in the flow of buffer back toward the negative electrode.) Most antibodies are gamma globulins. Therefore gamma globulins become more abundant following infections or immunizations

Serum LipidsBecause of their relationship to cardiovascular disease, the analysis of serum lipids has become an important health measure. The table shows the range of typical values as well as the values above (or below) which the subject may be at increased risk of developing atherosclerosis.

LIPIDTypical values (mg/dl) Desirable (mg/dl) Cholesterol (total)170–210 <200LDL cholesterol60–140 <100HDL cholesterol35–85 >40Triglycerides40–160 <160

Total cholesterol is the sum of HDL cholesterol LDL cholesterol and 20% of the triglyceride value

Note that high LDL values are bad, but high HDL values are good.

Using the various values, one can calculate acardiac risk ratio = total cholesterol divided by HDL cholesterol A cardiac risk ratio greater than 7 is considered a warning.

• Blood platelets (Thrombocytes)

Characteristics:

• Platelets are:

• Non-nucleated, round or oval cells .

• They are produced in the bone marrow from cells known as megakaryocytes.

• Normal count: 2-4 lacs /cubic mm of blood.

Steps of HemostasisSteps of Hemostasis

Vessel damage exposes collagen fibersVessel damage exposes collagen fibers

Platelets adhere to collagen & Platelets adhere to collagen & release factorsrelease factors

local vasoconstrictionlocal vasoconstriction & & platelet aggregationplatelet aggregation

decreased blood flowdecreased blood flow platelet plug formation platelet plug formation

Hemostasis

• Methods utilized1. vascular spasm

2. platelet plug formation

3. blood clotting (coagulation = formation of fibrin threads)

Overview of the Clotting Cascade

• General mechanism of blood coagulation• Blood clotting/coagulation takes place in three essential

steps-– In response to rupture of the vessel or damage to the

blood itself, a complex cascade of chemical reactions occur in the blood. The net result is formation of activated substances collectively called prothrombin activator.

– The prothrombin activator catalyzes the conversion of prothrombin into thrombin.

– The thrombin acts as an enzyme to convert fibrinogen into fibrin fibers that enmesh platelets, blood cells and plasma to form the clot.

Prothrombin Prothrombin activator(Ca++ )

Thrombin

Fibrinogen Fibrin monomer

Fibrin monomer or Clot

Anticoagulant drugs to treat thromboembolism

Drug Class Prototype Action Effect

AnticoagulantParenteral

Heparin Inactivation of clottingFactors

Prevent venousThrombosis

AnticoagulantOral

Warfarin Decrease synthesis ofClotting factors

Prevent venousThrombosis

Antiplateletdrugs

Aspirin Decrease plateletaggregation

Prevent arterialThrombosis

Thrombolytic Drugs

Streptokinase Fibinolysis Breakdown ofthrombi

•Anticoagulants suppress or prevent blood clotting.•Thrombolytic agents are injected to dissolve clots.

The ABO blood groups

• The most important in assuring a safe blood transfusion.

• The table shows the four ABO phenotypes ("blood groups") present in the human population and the genotypes that give rise to them.

Blood Group

Antigens on RBCs

Antibodies in Serum Genotypes

A A Anti-B AA or AO

B B Anti-A BB or BO

AB A and B Neither AB

O Neither Anti-A and anti-B OO

Why group A blood must never be given to a group B person?

Giving someone blood from the wrong ABO group could be fatal.

The anti-A antibodies in group B attack group A cells and vice versa.

• Blood group O negative is a different story.

Well, it gets more complicated here, because there's another antigen to be considered - the Rh antigen.

Some of us have it, some of us don't.

If it is present, the blood is RhD positive, if not it's RhD negative.

So, for example, some people in group A will have it, and will therefore be classed as A+ (or A positive).

While the ones that don't, are A- (or A negative).

And so it goes for groups B, AB and O.

The Rhesus (Rh) System

• Rh antigens are transmembrane proteins with loops exposed at the surface of red blood cells.

• They appear to be used for the transport of carbon dioxide and/or ammonia across the plasma membrane.

• They are named for the rhesus monkey in which they were first discovered.

• RBCs that are "Rh positive" express the antigen designated D.

• 85% of the population is RhD positive, the other 15% of the population is running around with RhD negative blood.

The Rhesus (Rh) System (Cont.)

Fibrinolysis

• Clot dissolved by activity of plasmin, an enzyme which hydrolyzes fibrin

Blood Grouping

• Determined by antigens (agglutinogens) on surface of RBCs

• Antibodies (agglutinins) can bind to RBC antigens, resulting in agglutination (clumping) or hemolysis (rupture) of RBCs

• Groups– ABO and Rh

ABO Blood Groups

Agglutination Reaction

Rh Blood Group

• First studied in rhesus monkeys• Types

– Rh positive: Have these antigens present on surface of RBCs

– Rh negative: Do not have these antigens present

• Hemolytic disease of the newborn (HDN)– Mother produces anti-Rh antibodies that cross

placenta and cause agglutination and hemolysis of fetal RBCs

Hemophilia• Inherited deficiency of clotting factors

– bleeding spontaneously or after minor trauma– subcutaneous & intramuscular hemorrhaging– nosebleeds, blood in urine, articular bleeding & pain

• Classic Hemophilia/ Hemophilia A: It occurs due to lacking of factor VIII (males only). It is the most common type of Hemophilia.

• Christmas Disease/ Hemophilia B: It occurs due to lacking of factor IX (males only).

• Hemophilia C (males & females)– less severe because alternate clotting activator exists

• Treatment is transfusions of fresh plasma or concentrates of the missing clotting factor.

• Rh blood types• Along with the O-A-B blood group system, the

Rh blood type system is also important in the transfusion of blood. The major difference between the O-A-B and Rh system is the following: In the O-A-B system the plasma agglutinins responsible for causing transfusion reactions develop spontaneously, whereas in the Rh system, spontaneous agglutinins never occur. Instead the person must first be massively exposed to an Rh antigen, such as by transfusion of blood containing the antigen, before enough agglutinins to cause a significant transfusion reaction will develop.

• Rh antigens-Rh positive and negative people• There are six common types of Rh antigen, each of

which is called an Rh factor. These are designated C, D, E, c, d, e.A person who has a C antigen does not have the c antigen, but the person missing the C antigen always has the c antigen. The same is true for the D-d and E-e antigens. Because of the manner of inheritance of these factors, each person has one of each pair of the three pairs of antigens.

• The type D antigen is widely prevalent in the population and considerably more antigen than the other Rh antigens. Therefore anyone who has this type of antigen is

• said to be Rh positive, whereas a person does not have type D antigen is said to be Rh negative.

A and B Antigens-Agglutinogens • Two antigens-type A and type-B-occur on the

surfaces of the RBC in a large proportion of human beings. It is these antigens (also called agglutinogen because they often cause blood cell agglutination) that cause most blood transfusion reaction. Because of the way these agglutinogens are inherited, people may have neither of them on their cells, these may have one, or they may have both simultaneously.

Major O-A-B Blood types:

• In transfusing blood from one person to another, the blood donors and recipients is normally classified into four major types, depending on the presence or absence of the two agglutinogens.When neither A or nor B agglutinogen is present, the blood type is O.When only type A agglutinogen is present, the blood is type A. When only type B agglutinogen is present, the blood is type B.When both A and B agglutinogen are present, the blood is type AB.

• AGGLUTININS:• When type A agglutinogen is not present in a

persons RBC, antibodies known as anti-A agglutinins develop in the plasma. When type B agglutinogen is not present in the RBC, antibodies known as anti-B agglutinins develop in the plasma. Group O blood, containing no agglutinogen contains both anti-A and anti-B agglutinins. Group A blood contains type A agglutinogen and anti-B agglutinins and Group B blood contains type B agglutinogen and anti-A agglutinins. Finally group AB blood contains both A ad B agglutinogen but no agglutinins.

• CLINICAL PICTURE OF ERYTHROBLASTOSIS FETALIS:

• The jaundiced erythroblastotic newborn is usually anemic at birth and the anti-Rh agglutinins from the mother usually circulate in the infant’s blood for 1 to 2 months after birth destroying more and more RBC.

• The hamatopoeitic tissue of the infant attempt to replace the hemolyzed RBC.The liver and spleen greatly enlarged and produces RBC in the same manner that they normally do in the middle trimester of gestation. Because of the rapid production of cells, many early forms of RBC, including many nucleated blastic forms, are passed from the bone marrow into circulatory system, and it is because of the presence of these nucleated blastic RBC that the disease is called erythroblastosis fetalis

• CLINICAL PICTURE OF ERYTHROBLASTOSIS FETALIS:

• The jaundiced erythroblastotic newborn is usually anemic at birth and the anti-Rh agglutinins from the mother usually circulate in the infant’s blood for 1 to 2 months after birth destroying more and more RBC.

• The hamatopoeitic tissue of the infant attempt to replace the hemolyzed RBC.The liver and spleen greatly enlarged and produces RBC in the same manner that they normally do in the middle trimester of gestation. Because of the rapid production of cells, many early forms of RBC, including many nucleated blastic forms, are passed from the bone marrow into circulatory system, and it is because of the presence of these nucleated blastic RBC that the disease is called erythroblastosis fetalis

• Erythroblastosis fetalis:• It is a clinical condition characterized by high

erythroblast count in fetus.• CAUSE:• When Rh positive fetus develops in Rh negative

mother, anti-D develops in mother’s blood in response to antigen-D in fetus. As a result agglutination takes place and rapid destruction of fetus RBC occurs, releasing hemoglobin into the blood. The fetus’s macrophages then convert the hemoglobin into bilirubin, which causes the baby’s skin to become yellow.

• Acute hemolysis occurs in some transfusion reaction:

• Sometimes when recipient and donor bloods are mismatched, immediate hemolysis of RBC occurs in the circulating blood. In this case the antibodies cause lysis of RBC by activating the complement system, which releases proteolytic enzymes that rupture the cell membranes.