CIRCULATORY SYSTEM Blood Composition and Function What

CIRCULATORY SYSTEM Blood Composition and Function

What is Blood? • Blood is a connective tissue • Its volume is 5 -6 L in males and 4 -5 L in females • It is slightly alkaline, with a p. H of ~ 7. 4 • Its color varies from bright to dark red • It has a salty metallic taste

Whole Blood • Blood flowing freely through the human body. • If it is outside the body and with an anticoagulant and not separated into the liquid portion & the cells, it is still called whole blood. • Example: a CBC requires EDTA whole blood.

Serum • Serum is plasma without the clotting factors, mainly the fibrinogen. • So serum, on standing does not clot. Usually, to acquire serum, all clotting agents in plasma are removed through progressive centrifuging, or we can get a blood sample and after allowing it to clot, the supernatant is taken. • Serum includes all the other electrolytes, proteins not used in the clotting process, drugs and toxins. Human serum is usually used for the purpose of diagnostic testing. • Other animal seras are used as anti venom, anti toxins, and vaccinations. It does not contain fibrinogen, therefore coagulation tests cannot be performed because the coagulation factors (fibrinogen) have been used in the process of clot formation.

Plasma • Plasma - If anticoagulants are added to the tube: EDTA, Sodium citrate, heparin, etc. , the blood will not clot. • Plasma is the basic watery part of the blood. We are able to observe plasma, if we stand a column of blood for about one hour, we can see the precipitation of red cells and white cells with a supernatant straw colored liquid. • This liquid is the plasma. • Plasma contains fibrinogen, an important factor in the clotting process and other major factors of clotting. Thus, on standing this straw colored liquid tends to clump.

Plasma • This plasma can be spun, so the protein materials with heavier masses tend to precipitate down, leaving better purified plasma. • Plasma is required for diagnostic investigation and especially for therapeutic transfusions in people, who are hypovolemic, deficient in clotting factors, etc. • A lesser clot prone plasma is available as cryo poor plasma (CPP), and the removed clotting agents are used in the treatment of hemophiliacs as cryo precipitate. • The use of an anticoagulant preserves the fibrinogens in the plasma, so it may be used in a coagulation test.

Difference between Plasma and Serum • Both plasma and serum are derivatives of blood. Both contain electrolytes, other proteins, drugs, hormones and toxins. Both can be acquired from centrifugation and purity depends on the duration and the frequency of this process. • Both can be used for diagnostic and therapeutic purposes. • But plasma is serum with fibrinogen and clotting factors. • So plasma tends to discolor on standing, whereas serum does not. • Separation of plasma is relatively easy and inexpensive, whereas separation of serum requires higher levels of expertise and expenses.

• Plasma is most commonly used for therapeutic purposes where, either the full plasma (Fresh frozen plasma), clotting factor removed (Cryo poor plasma) or the clotting factors itself (Cryo precipitate) can be used. Serum is most commonly used for diagnostic purposes. • Animal sera are used in humans for therapeutic purposes. • Plasma can be considered as the crude product of precipitation of blood whereas serum is the refined plasma minus the fibrinogen and the other clotting factors.

Function 3 major functions • Transportation • Regulation • Protection

Transportation • Respiratory Red blood cells or erythrocytes transport Oxygen from lungs to cells and Carbon dioxide from cells to lungs • Nutritive Blood absorb nutrients from digested foods in gastrointestinal tract and transport to all the cells in body

• Excretory Metabolic wastes, excess water and ions , and other molecules not needed by the body are carried by the blood to the kidneys and excreted in the urine

Regulation • Hormonal Blood carries hormones from their site of origin to distant target tissues , where they perform the regulatory functions • Temperature Blood is responsible to carry body heat to the surface in high temperature environment as well as to keep body heat in within low temperature environment

Protection • Clotting The clotting mechanism protects against blood loss when vessels are damaged • Immune The immune function of blood is performed by the leukocytes that protects against many disease causing agents

Composition of the Blood • Blood consists of formed elements that are suspended and carried in a fluid called plasma • The formed elements - Erythrocytes Oxygen transport - Leukocytes Immune defence - Platelets Blood clotting

Plasma • Straw colored fluid made of water (~90%), other contents include: • Proteins make the bulk of the solutes: Albumins (60%), manufactured in the liver are the most abundant Globulins (36%) are immune bodies Fibrinogen (4%) for blood clotting

• Nutrients: glucose, amino acids, lipids, cholesterol • Electrolytes: Na+, K+, Ca++, Mg++, H+, Cl-, HCO 3 -, PO 4 --, SO 4 -- • Waste: urea, creatinine, uric acid, bilirubin • Gases: O 2 , CO 2 , N 2 • Protein bound hormones • Plasma without clotting factors is called “serum”

RBC/ Erythrocytes • An RBC is a 7. 5 micron disc shaped body with a central depression • The cell is without a nucleus or mitochondria • AN RBC contains hemoglobin and filamentous proteins attached to the cell wall to impart flexibility on it • Life span 120 days

• Erythrocytes are produced in bone marrow • Older erythrocytes are removed from the circulation by phagocytic cells in the liver, spleen and bone marrow.

• Antigens are embedded in the cell membrane, they decide the blood group • The RBC cytoplasm provides energy to maintain intracellular homeostasis • This energy is generated mostly through anaerobic glycolysis • RBCs function is gas exchange: O 2 to the tissues and CO 2 to the lungs

White Blood Cells/Leukocytes • Leukocytes contain nuclei and mitochondria and can move in an amoeboid fashion • Because of their amoeboid ability, leukocytes can squeeze through pores in capillary walls and move to a site of infection. • Produced in bone marrow and destructed in spleen

Types • The total number of WBCs is 4000 to 11, 000/mm 3 • There two main types of WBCs: granulucytes and agranulocytes

• Granulocytes, are of three types: Neutrophils (polymorphs) 50 -70%, destroy bacteria Eosinophils, 2 -4% bilobed nuclei, attack parasites Basophils, 1% in peripheral blood, reside in the tissues, contain histamine, involved in hypersensitivity reaction

• Agranulocytes are of two types Lymphocytes, the smallest and second most abundant T cells (80%) mediate cellular immunity B cells mediate humoral immunity Monocytes, the largest, migrate to the tissues and become macrophages involved in cellular immunity

Neutrophils

Monocytes Eosinophils

Lymphocytes Basophils

Platelets • Platelets are only about 20% of the diameter of red blood cells, the most numerous cell of the blood. • The normal platelet count is 150, 000350, 000 per microliter of blood • Platelets are produced in bone marrow and destroyed in the spleen and liver • Life span 5 to 9 days

• They are fragments of cells called megakaryocytes, they have no nuclei but like leukocytes are capable of amoeboid movements • Platelets play an important role in blood clotting • They constitute most of the mass of the clot, and phospholipids in their cell membranes activate the clotting factors in plasma that result in threads of fibrin, which reinforce the platelet plug.

• Platelets that attach together in a blood clot release serotonin , a chemical that stimulates constriction of blood vessel. Platelets

Red Blood Cell Antigens and Blood Typing

ABO System • There are several groups of red blood cell antigens, but the major group is known as ABO system • In terms of the antigens present on the red blood cell surface , a person may be : Type A – with only A antigens Type B – with only B antigens Type AB – with both A and B antigens Type O – with neither A nor B antigens

Plasma Antibodies Type A – with only B antibodies Type B – with only A antibodies Type AB – with neither A nor B antibodies Type O – with both A and B antibodies

Rh ( Rhesus ) factor • Another group of antigens found on the red blood cells • People who have these antigens are said to be Rh positive, whereas those who do not are Rh negative

Blood Clotting • When a blood vessel is injured, a number of physiological mechanisms are activated that promote hemostasis • Mechanisms are: Vasoconstriction Formation of a platelet plug Production of a web of fibrin proteins that penetrates and surrounds the platelet plug

Functions of platelets • In the absence of vessel damage, platelets are repelled from each other and from the endothelial lining of vessels • The repulsion of platelets from an intact endothelium is believed to be due to prostacyclin produced with in the endothelium

• Damage to the endothelium of vessels leads to secretion of Von Willebrand factor by endothelial cells • This factor initiate the adhesion of platelets to the damaged vessel • When the platelets adhere to the vessel, platelets release ADP ( Adenosin Diphosphate ), serotonin and Thromboxane A 2

• Serotonin and Thromboxane A 2 stimulate vasoconstriction, which helps to decrease blood flow to the injured blood vessel • Phospholipids that are exposed on the platelet membrane participate in the activation of clotting factors • The release of ADP and Thromboxane A 2 from platelets make other platelets also sticky • This produces a platelet plug

Clotting Factors: Formation of Fibrin • The platelet plug is strengthen by a mesh work of insoluble protein fibers known as fibrin • Blood clots contain platelets and fibrin, and they usually contain trapped red blood cells that give the clot a red color • Finally, contraction of the platelet mass in the process of clot retraction forms more effective and more compact plug

• The conversion of fibrinogen in to fibrin may occur via 2 pathways Intrinsic pathway Extrinsic pathway • By both these pathways clotting factors get activated • This leads to activation of inactive enzyme Prothrombin to active enzyme Thrombin • Thrombin converts the soluble protein fibrinogen in to fibrin which form the mesh work supporting platelet plug.

Dissolution of clots • As damaged blood vessel wall is repaired factor XII promotes conversion of Kallikrein from inactive form to active form • This Kallikrein convert inactive Plasminogen in to active Plasmin • Plasmin is an enzyme that digests fibrin into split products