BLOOD

Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells. In vertebrates, Blood is composed of blood cells suspended in a liquid called blood plasma. Plasma, which constitutes 55% of blood fluid. The blood cells are mainly red blood cells also called RBCs or erythrocytes and white blood cells also called Leucocytes and platelets or thrombocytes.The most abundant cells in vertebrate blood are red blood cells.

BLOOD CELLS
A blood cell, also called a hematocyte, is a cell produced by haematopoiesis and normally found in blood. In mammals, these fall into three general categories: red blood cells Erythrocytes white blood cells Leukocytes platelets Thrombocytes

Together, these three kinds of blood cells add up to a total 45% of the blood tissue by volume, with the remaining 55% of the volume composed of plasma, the liquid component of blood.

RED BLOOD CELLS (ERYTHROCYTES)

Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen (O2) to the body tissues via the blood flow through the circulatory system. These cells cytoplasm is rich in haemoglobin, an iron-containing biomolecule that can bind oxygen and is responsible for the blood's red color.

STRUCTURE
In humans, mature red blood cells are flexible biconcave disks that lack a cell nucleus and most organelles. A typical human erythrocyte has a disk diameter of 68 m and a thickness of 2 m, being much smaller than most other human

cells. Adult humans have roughly 23 1013 (20-30 trillion) red blood cells at any given time, comprising approximately one quarter of the total human body cell number (women have about 4 to 5 million erythrocytes per microliter (cubic millimeter) of blood and men about 5 to 6 million. Human red blood cells take on average 20 seconds to complete one cycle of circulation. The blood's red color is due to the spectral properties of the hemic iron ions in hemoglobin. Each human red blood cell contains approximately 270 million of these hemoglobin biomolecules, each carrying four heme groups; hemoglobin comprises about a third of the total cell volume. This protein is responsible for the transport of more than 98% of the oxygen (the remaining oxygen is carried dissolved in the blood plasma).

RED BLOOD CELLS

LIFE CYCLE
Human erythrocytes are produced through a process named erythropoiesis, developing from committed stem cells to mature erythrocytes in about 7 days. When matured, these cells live in blood circulation for about 100 to 120 days. At the end of their lifespan, they become senescent, and are removed from circulation.

WHITE BLOOD CELL (LEUCOCYTES)

White blood cells, or leukocytes are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a hematopoietic stem cell.

Leukocytes are found throughout the body, including the blood and lymphatic system. There are normally between 4109 and 1.11010 white blood cells in a litre of blood, and ranging from 7 and 21 micrometres in diameter, they make up approximately 1% of blood in a healthy adult.

WHITE BLOOD CELLS

TYPES OF WHITE BLOOD CELLS

There are several different types of white blood cells. They all have many things in common, but are all distinct in form and function. Two major types of WBCS are Granulocytes and Agranulocytes.

GRANULOCYTES
Leukocytes characterised by the presence of differently staining granules in their cytoplasm when viewed under light microscopy. There are three types of granulocytes: neutrophils, basophils, and eosinophils, which are named according to their staining properties.

NEUTROPHILS
Neutrophils defend against bacterial or fungal infection and other very small inflammatory processes that are usually first responders to microbial

infection.their activity and death in large numbers forms pus. They have a multilobed nucleus that may appear like multiple nuclei, hence the name polymorphonuclear leukocyte. Neutrophils are the most common cell type seen in the early stages of acute inflammation, and make up 60-70% of total leukocyte count in human blood. Neutrophils are very active in phagocytosing bacteria and are present in large amount in the pus of wounds. The life span of a circulating human neutrophil is about 5.4 days.

NEUTROPHILS

EOSINOPHILS
Eosinophils primarily deal with parasitic infections. Eosinophils are also the predominant inflammatory cells in allergic reactions. The most important causes of eosinophilia include allergies such as asthma, hay fever, and hives; and also parasitic infections. In general, their nucleus is bi-lobed. The cytoplasm is full of granules that assume a characteristic pink-orange color with eosin stain.

BASOPHILS
Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing vasodilation. The nucleus is bi- or tri-lobed, but it is hard to see because of the number of coarse granules that hide it. They are characterized by their large blue granules.

BASOPHILS

AGRANULOCYTES
Leukocytes characterized by the apparent absence of granules in their cytoplasm. Although the name implies a lack of granules these cells do contain non-specific azurophilic granules, which are lysosomes. The cells include lymphocytes, monocytes, and macrophages. TYPES OF AGRANULOCYTES Monocytes Monocytes share the "vacuum cleaner" (phagocytosis) function of neutrophils, but are much longer lived as they have an additional role: they present pieces of pathogens to T cells so that the pathogens may be recognized again and killed, or so that an antibody response may be mounted. Monocytes eventually leave the bloodstream to become tissue macrophages, which remove dead cell debris as well as attacking microorganisms.

MONOCYTES

Lymphocytes Lymphocytes are much more common in the lymphatic system. Lymphocytes are distinguished by having a deeply staining nucleus that may be eccentric in location, and a relatively small amount of cytoplasm. The blood has three types of lymphocytes:

B-Cells. T-Cells. Natural Killer Cells. All these three kind of cells participate in Immune responses via using different mechanisms.

PLATELETS
Platelets, or thrombocytes are small, irregularly shaped clear cell fragments (i.e. cells that do not have a nucleus containing DNA), 23 m in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days. Platelets are a natural source ofgrowth factors. They circulate in the blood of mammals and are involved in hemostasis, leading to the formation of blood clots. If the number of platelets is too low, excessive bleeding can occur. However, if the number of platelets is too high, blood clots can form (thrombosis), which may obstruct blood vessels and result in such events as a stroke, myocardial infarction, pulmonary embolism or the blockage of blood vessels to other parts of the body, such as the extremities of the arms or legs.

PLATELETS

PLASMA PROTEINS
Blood proteins, also termed serum proteins or plasma proteins, are proteins found in blood plasma. Serum total protein in blood is 7g/dl. They serve many different functions, including circulatory transport molecules for lipids hormones, vitamins and metals. enzymes, complement components, protease inhibitors, and kinin precursors. regulation of acellular activity and functioning and in the immune system.

Classification of plasma proteins

Blood proteins

Normal level

Function

Albumins

3.5-5.0 g/dl 60%

create oncotic molecules

pressure and

transports

other

immunoglobulins

1.0-1.5 g/dl 18% participate in immune system

Fibrinogens

0.2-0.45 g/dl 4% blood coagulation

alpha 1-antitrypsin

neutralize trypsin that the digestive system

has

leaked

from

Regulatory proteins

<1% Regulation of few gene expression

60% of plasma proteins are made up of the protein albumin, which are major contributors to osmotic pressure of plasma which assists in the transport of lipids and steroid hormones. Globulins make up 35% of plasma proteins and are used in the transport of ions, hormones and lipids assisting in immune function. 4% is fibrinogen which is essential in the clotting of blood and can be converted into insoluble fibrin. Regulatory proteins which make up less than 1% of plasma proteins are proteins such as enzymes, proenzymes and hormones. All the plasma proteins are synthesized in liver except gamma globulins.

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.

COAGULATION PATHWAYS
There are two pathways of coagulation: Tissue factor pathway or extrinsic pathway. Contact activation pathway or intrinsic pathway.

TISSUE FACTOR PATHWAY (EXTRINSIC)

The main role of the tissue factor pathway is to generate a "thrombin burst," a process by which thrombin, the most important constituent of the coagulation cascade in terms of its feedback activation roles, is released instantaneously. FVIIa circulates in a higher amount than any other activated coagulation factor. Following damage to the blood vessel, FVII leaves the circulation and comes into contact with tissue factor (TF) expressed on tissue-factorbearing cells (stromal fibroblasts and leukocytes), forming an activated complex (TF-FVIIa). TF-FVIIa activates FIX and FX. FVII is itself activated by thrombin, FXIa, FXII and FXa. The activation of FX (to form FXa) by TF-FVIIa is almost immediately inhibited by tissue factor pathway inhibitor (TFPI). FXa and its co-factor FVa form the prothrombinase complex, which activates prothrombin to thrombin.

Thrombin then activates other components of the coagulation cascade, including FV and FVIII (which activates FXI, which, in turn, activates FIX), and activates and releases FVIII from being bound to vWF. FVIIIa is the co-factor of FIXa, and together they form the "tenase" complex, which activates FX; and so the cycle continues. ("Tenase" is a contraction of "ten" and the suffix "-ase" used for enzymes.)

CONTACT ACTIVATION PATHWAY (INTRINSIC)

The contact activation pathway begins with formation of the primary complex on collagen by high-molecular-weight kininogen (HMWK),prekallikrein, and FXII (Hageman factor). Prekallikrein is converted to kallikrein and FXII becomes FXIIa. FXIIa converts FXI into FXIa. Factor XIa activates FIX, which with its cofactor FVIIIa form the tenase complex, which activates FX to FXa. The minor role that the contact activation pathway has in initiating clot formation can be illustrated by the fact that patients with severe deficiencies of FXII, HMWK, andprekallikrein do not have a bleeding disorder. Instead, contact activation system seems to be more involved in inflammation.

FINAL COMMON PATHWAY

Thrombin has a large array of functions. Its primary role is the conversion of fibrinogen to fibrin, the building block of a hemostatic plug. In addition, it activates Factors VIII and V and their inhibitor protein C (in the presence of thrombomodulin), and it activates Factor XIII, which forms covalent bonds that crosslink the fibrin polymers that form from activated monomers. Following activation by the contact factor or tissue factor pathways, the coagulation cascade is maintained in a prothrombotic state by the continued activation of FVIII and FIX to form the tenase complex, until it is down-regulated by the anticoagulant pathways.

Extrinsic and intrinsic pathway of coagulation

DISORDERS ASSOCIATED TO BLOOD

Dozens of different diseases can involve the blood. Blood disorders can affect any of the three main components of blood: Red blood cells, which carry oxygen to the body's tissues. White blood cells, which fight infections. Platelets, which help blood to clot. Blood disorders may be inherited or genetic. Blood disorders can also affect the liquid portion of blood, called plasma. Some common blood disorders are given below:

ANEMIA
People with anemia have a low number of red blood cells. Mild anemia often causes no symptoms. More severe anemia can cause fatigue, pale skin, and shortness of breath with exertion. Iron-deficiency anemia: Iron is necessary for the body to make red blood cells. Low iron intake and loss of blood due to menstruationare the most common causes of iron-deficiency anemia. Treatment includes iron pills, or rarely blood transfusion. Anemia of chronic disease: People with chronic kidney disease or other chronic diseases tend to develop anemia. Anemia of chronic disease does not usually require treatment. Injections of a synthetic hormone (Epogen, Procrit) to stimulate the production of blood cells or blood transfusions may be necessary in some people with this form of anemia. Pernicious anemia (B12 deficiency): An autoimmune condition that prevents the body from absorbing enough B12 in the diet. Besides anemia, nerve damage(neuropathy) can eventually result. High doses of B12 prevent long-term problems. Aplastic anemia: In people with aplastic anemia, the bone marrow does not produce enough blood cells, including red blood cells. A viral infection, drug side effect, or an autoimmune condition can cause aplastic anemia. Blood transfusions, and even a bone marrow transplant, may be required to treat aplastic anemia. Autoimmune hemolytic anemia: In people with this condition, an overactive immune system destroys the body's own red blood cells, causing anemia. Medicines that suppress the immune system, such as prednisone, may be required to stop the process. Thalassemia: This is a genetic form of anemia that mostly affects people of Mediterranean heritage. Most people have no symptoms and require no treatment. Others may need regular blood transfusions to relieve anemia symptoms. Sickle cell anemia: A genetic condition that affects mostly African-Americans. Periodically, red blood cells change shape, and block blood flow. Severe pain and organ damage can occur. Polycythemia vera : The body produces too many blood cells, from an unknown cause. The excess red blood cells usually create no problems, but cause blood clots in some people.

OTHER DISORDERS RELATED TO BLOOD

HAEMOPHILIA Haemophilia is a group of hereditary genetic disorders that impair the body's ability to control blood clotting or coagulation, which is used to stop bleeding when a blood vessel is broken. Haemophilia lowers blood plasma clotting factor levels of the coagulation factors needed for a normal clotting process. Thus when a blood vessel is injured, a temporary scab does form, but the missing coagulation factors prevent fibrin formation, which is necessary to maintain the blood clot. A haemophiliac does not bleed more intensely than a person without it, but can bleed for a much longer time. LEUKOPENIA Leukopenia is a decrease in the number of white blood cells (leukocytes) found in the blood, which places individuals at increased risk of infection. NEUTROPENIA Neutropenia, is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell. Neutrophils usually make up 50-70% of circulating white blood cells and serve as the primary defense against infections by destroying bacteria in the blood. Hence, patients with neutropenia are more susceptible to bacterial infections BASOPENIA Basopenia (or basocytopenia) is a form of agranulocytosis associated with a deficiency of basophils. EOSIONOPENIA Eosinopenia is a form of agranulocytosis where the number of eosinophil granulocyte is lower than expected. LEUKOCYTOSIS Leukocytosis is a raised white blood cell count (the leukocyte count) above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, and is observed in certain parasitic infections.

MONOCYTOSIS Monocytosis is an increase in the number of monocytes circulating in the blood. [1] Monocytes are white blood cells that give rise to macrophages and dendritic cells in the immune system. NEUTOROPHILA Neutrophilia or neutrophil leukocytosis describes a high number of neutrophil granulocytesin blood. EOSINOPHILIA Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45109/L (450/l). Several causes are known, with the most common being some form of allergic reaction or parasitosis. BASOPHILIA Basophilia is a condition where the basophil quantity is abnormally elevated (more than 1010basophils per liter of blood). Basophilia as an isolated finding is uncommon. However it is a common feature of myeloproliferative disorders and particularly prominent in chronic myelogenous leukemia. HEMATOLOGICAL MALIGNANCIES Hematological malignancies are the types of cancer that affect blood, bone marrow, andlymph nodes. As the three are intimately connected through the immune system, a disease affecting one of the three will often affect the others as well. If the hematological malignancies are located in the blood then the disease is said to be Leukemia.