Blood_as_a_Circulatory_Fluid_&_the_Dynamics_of_Blood_&_Lymph (2).pdf

Physiology Cardiovascular System Chapter 31 | Blood as a Circulatory Fluid & the Dynamics of Blood & Lymph Flow Cardiovascular System | Blood Contents : Introduction 5 Blood As A Circulatory Fluid 8 Bone Marrow 10 Whit...

Physiology Cardiovascular System Chapter 31 | Blood as a Circulatory Fluid & the Dynamics of Blood & Lymph Flow Cardiovascular System | Blood Contents : Introduction 5 Blood As A Circulatory Fluid 8 Bone Marrow 10 White Blood Cells 18 Platelets 24 Red Blood Cells 26 Hemoglobin 31 Reactions Of Hemoglobin 37 Synthesis Of Hemoglobin 42 Catabolism Of Hemoglobin 45 Cardiovascular System | Blood Contents : Blood Types 47 The ABO System 49 Transfusion Reactions 56 The Rh Group 65 Hemolytic Disease Of The Newborn 70 Plasma 80 Plasma Proteins 83 Hemostasis 86 Response To Injury 88 Cardiovascular System | Blood Contents : The Clotting Mechanism 91 Anticlotting Mechanisms 94 Lymph 98 Structural Features Of The Circulation 101 Endothelium 103 Vascular Smooth Muscle 104 Chapter Summary 106 Cardiovascular System | Blood Introduction : The circulatory system supplies inspired O2 as well as substances absorbed from the gastrointestinal tract to the tissues, returns CO2 to the lungs and other products of metabolism to the kidneys, functions in the regulation of body temperature, and distributes hormones and other agents that regulate cell function. The blood, the carrier of these substances, is pumped through a closed system of blood vessels by the heart. Cardiovascular System | Blood The blood flow to each tissue is regulated by local chemical and general neural and humoral mechanisms that dilate or constrict its vessels. Blood is a specialized type of connective tissue, red in color, syrupy fluid which has specific gravity 1.055 and the viscosity 2.5 times that of water. Blood is alkaline (PH=7.4) and appear scarlet red when taken from arteries and purplish from veins. The difference in color is due to its O2 content. Cardiovascular System | Blood Blood consists of a protein-rich fluid known as plasma, in which are suspended cellular elements: white blood cells, red blood cells, and platelets. The normal total circulating blood volume is about 8% of the body weight (5600 mL in a 70-kg man). About 55% of this volume is plasma. Blood plays a role in maintaining the cellular environment by serving as a transport medium of the body. The various functions of blood result from specialization within the cellular elements or the plasma or the interaction between the two. Cardiovascular System | Blood Blood As A Circulatory Fluid: Blood consists of a protein-rich fluid known as plasma, in which are suspended cellular elements: white blood cells, red blood cells, and platelets. The normal total circulating blood volume is about 8% of the body weight (5600 mL in a 70-kg man). About 55% of this volume is plasma. Cardiovascular System | Blood Cardiovascular System | Blood Bone Marrow : In the adult, red blood cells, many white blood cells, and platelets are formed in the bone marrow. In the fetus, blood cells are also formed in the liver and spleen, and in adults such extramedullary hematopoiesis may occur in diseases in which the bone marrow becomes destroyed or fibrosed. In children, blood cells are actively produced in the marrow cavities of all the bones. Cardiovascular System | Blood Cardiovascular System | Blood By age 20, the marrow in the cavities of the long bones, except for the upper humerus and femur, has become inactive. Active cellular marrow is called red marrow; inactive marrow that is infiltrated with fat is called yellow marrow. The bone marrow is actually one of the largest organs in the body, approaching the size and weight of the liver. It is also one of the most active. Cardiovascular System | Blood Cardiovascular System | Blood Normally, 75% of the cells in the marrow belong to the white blood cell–producing myeloid series and only 25% are maturing red cells, even though there are over 500 times as many red cells in the circulation as there are white cells. This difference in the marrow reflects the fact that the average life span of white cells is short, whereas that of red cells is long. Cardiovascular System | Blood Hematopoietic stem cells (HSCs) are bone marrow cells that are capable of producing all types of blood cells. They differentiate into one or another type of committed stem cells (progenitor cells). These in turn form the various differentiated types of blood cells. There are separate pools of progenitor cells for megakaryocytes, lymphocytes, erythrocytes, eosinophils, and basophils; neutrophils and monocytes arise from a common precursor. Cardiovascular System | Blood Cardiovascular System | Blood The bone marrow stem cells are also the source of osteoclasts, Kupffer cells mast cells, dendritic cells, and Langerhans cells. The HSCs are few in number but are capable of completely replacing the bone marrow when injected into a patient whose own bone marrow has been entirely destroyed. Cardiovascular System | Blood White Blood Cells: Normally, human blood contains 4000–11,000 white blood cells per microliter (Table 31–1). Cardiovascular System | Blood TABLE 31–1 Normal values for the cellular elements in human blood. Approximate Percentage Cells/μL Cell Normal of Total (average) Range White Cells Total white blood cells 9000 4000–11,000 … Granulocytes Neutrophils 5400 3000-6000 50-70 Eosinophils 275 150-300 1-4 Basophils 35 0-100 0.4 Lymphocytes 2750 1500-4000 20-40 Cardiovascular System | Blood TABLE 31–1 Normal values for the cellular elements in human blood. Approximate Percentage Cells/μL Cell Normal of Total (average) Range White Cells Monocytes 540 300-600 2-8 Erythrocytes Females 4.8 × 106 … … Males 5.4 × 106 … … 200,000– Platelets 300,000 … 500,000 Cardiovascular System | Blood Of these, the granulocytes (polymorphonuclear leukocytes,(PMNs) are the most numerous. Young granulocytes have horseshoe-shaped nuclei that become multilobed as the cells grow older (Figure). Most of them contain neutrophilic granules (neutrophils), but a few contain granules that stain with acidic dyes (eosinophils), and some have basophilic granules (basophils) Cardiovascular System | Blood Cardiovascular System | Blood The other two cell types found normally in peripheral blood are lymphocytes, which have large round nuclei and scanty cytoplasm, and monocytes, which have abundant agranular cytoplasm and kidney-shaped nuclei. Acting together, these cells provide the body with the powerful defenses against tumors and viral, bacterial, and parasitic infections. Cardiovascular System | Blood Platelets: Platelets are small, granulated bodies that aggregate at sites of vascular injury. They lack nuclei and are 2–4 μm in diameter). There are about 300,000/μL of circulating blood, and they normally have a half-life of about 4 days. The megakaryocytes, giant cells in the bone marrow, form platelets by pinching off bits of cytoplasm and extruding them into the circulation. Cardiovascular System | Blood Between 60% and 75% of the platelets that have been extruded from the bone marrow are in the circulating blood, and the remainder are mostly in the spleen. Splenectomy causes an increase in the platelet count (thrombocytosis). Cardiovascular System | Blood Red Blood Cells: The red blood cells (erythrocytes) carry hemoglobin in the circulation. They are biconcave disks that are manufactured in the bone marrow. In mammals, they lose their nuclei before entering the circulation. In humans, they survive in the circulation for an average of 120 days. The average normal red blood cell count is 5.4 million/μL in men and 4.8 million/μL in women. Cardiovascular System | Blood The number of red cells is also conveniently expressed as the hematocrit, or the percentage of the blood, by volume, that is occupied by erythrocytes. Each human red blood cell is about 7.5 μm in diameter and 2 μm thick, and each contains approximately 29 pg of hemoglobin (Table 31-2). Cardiovascular System | Blood TABLE 31–2: Characteristics of human red cells. Note: Cells with MCVs > 95 fL are called macrocytes. Cells with MCVs < 80 fL are called microcytes. Cells with MCHCs < 25 g/dL are called hypochromic. Cardiovascular System | Blood There are thus about 3 × 1013 red blood cells and about 900 g of hemoglobin in the circulating blood of an adult man. The feedback control of erythropoiesis by erythropoietin hormone released by renal tissue in presence of low O2 content in blood. Cardiovascular System | Blood Hemoglobin Cardiovascular System | Blood Hemoglobin: The red, oxygen-carrying pigment in the red blood cells of vertebrates is hemoglobin, a protein with a molecular weight of 64,450. Hemoglobin is a globular molecule made up of four subunits. Cardiovascular System | Blood Each subunit contains a heme moiety conjugated to a polypeptide. Heme is an iron containing porphyrin derivative. The polypeptides are referred to collectively as the globin portion of the hemoglobin molecule. There are two pairs of polypeptides in each hemoglobin molecule. In normal adult human hemoglobin (hemoglobin A), the two polypeptides are called α chains and β chains. Cardiovascular System | Blood Cardiovascular System | Blood Thus, hemoglobin A is designated α2β2. Not all the hemoglobin in the blood of normal adults is hemoglobin A. About 2.5% of the hemoglobin is hemoglobin A2, in which β chains are replaced by δ chains (α2δ2). The δ chains contain 10 individual amino acid residues that differ from those in β chains. Cardiovascular System | Blood There are small amounts of hemoglobin A derivatives closely associated with hemoglobin A that represent glycated hemoglobins. HbA1a , HbA1b , HbA1c one of these, hemoglobin A1c (HbA1c), has a glucose attached to the terminal valine in each β chain and is of special interest because it increases in the blood of patients with poorly controlled diabetes mellitus and is measured clinically as a marker of the progression of that disease and/or the effectiveness of treatment. Cardiovascular System | Blood Reactions Of Hemoglobin: O2 binds to the Fe2+ in the heme moiety of hemoglobin to form oxyhemoglobin. The affinity of hemoglobin for O2 is affected by pH, temperature, and the concentration in the red cells of 2,3-bisphosphoglycerate (2,3-BPG). 2,3-BPG λ arise in temperature or fall in PH or an increase in the concentration of 2,3-BPG lower the affinity of hemoglobin for O2 causing more O2 to be liberated and H+ compete with O2 for binding to deoxygenated hemoglobin, decreasing the affinity of hemoglobin for O2 by shifting the positions of the four peptide chains (quaternary structure). Cardiovascular System | Blood When blood is exposed to various drugs and other oxidizing agents in vitro or in vivo, the ferrous iron (Fe2+) that is normally present in hemoglobin is converted to ferric iron (Fe3+), forming methemoglobin. Methemoglobin is dark-colored, and when it is present in large quantities in the circulation, it causes a dusky discoloration of the skin resembling cyanosis. Cardiovascular System | Blood Cardiovascular System | Blood Some oxidation of hemoglobin to methemoglobin occurs normally, but an enzyme system in the red cells, the dihydronicotinamide adenine dinucleotide (NADH)- methemoglobin reductase system, converts methemoglobin back to hemoglobin. Carbon monoxide reacts with hemoglobin to form carbon monoxyhemoglobin (carboxyhemoglobin). The affinity of hemoglobin for O2 is much lower than its affinity for carbon monoxide, which consequently displaces O2 on hemoglobin, reducing the oxygen-carrying capacity of blood. Cardiovascular System | Blood Cardiovascular System | Blood Synthesis Of Hemoglobin: The average normal hemoglobin content of blood is 16 g/dL in men and 14 g/dL in women, all of it in red cells. In the body of a 70-kg man, there are about 900 g of hemoglobin, and 0.3 g of hemoglobin is destroyed and 0.3 g synthesized every hour. The heme portion of the hemoglobin molecule is synthesized from glycine and succinyl-CoA (Clinical Box 31–2) Cardiovascular System | Blood Clinical box 31–2: Abnormalities of Hemoglobin Production There are two major types of inherited disorders of hemoglobin in humans: The hemoglobinopathies, in which abnormal globin polypeptide chains are produced The thalassemias and related disorders, in which the chains are normal in structure but produced in decreased amounts or absent because of defects in the regulatory portion of the globin genes.. Cardiovascular System | Blood In one of the most common examples, hemoglobin S, the α chains are normal but the β chains have a single substitution of a valine residue for one glutamic acid, leading to sickle cell anemia. The cell assume a sickle shape , easily ruptured and the Hb – s loss its ability to carry O2 he rigid shape of the sickle cell inhibit their movement through the capillaries so they stick forming a pile behind the stuck cells that inhibit O2 supply to the tissue. Cardiovascular System | Blood Catabolism Of Hemoglobin: When old red blood cells are destroyed by tissue macrophages, the globin portion of the hemoglobin molecule is split off, and the heme is converted to biliverdin. In humans, most of the biliverdin is converted to bilirubin and excreted in the bile. The iron from the heme is reused for hemoglobin synthesis. Exposure of the skin to white light converts bilirubin to lumirubin, which has a shorter half-life than bilirubin. Cardiovascular System | Blood Phototherapy (exposure to light) is of value in treating infants with jaundice due to hemolysis. Iron is essential for hemoglobin synthesis; if blood is lost from the body and the iron deficiency is not corrected, iron deficiency anemia results. Blood Types Cardiovascular System | Blood Blood Types: The membranes of human red cells contain a variety of blood group antigens, which are also called agglutinogens. The most important and best known of these are the A and B antigens, but there are many more. Cardiovascular System | Blood The ABO System: The A and B antigens are inherited as mendelian dominants, and individuals are divided into four major blood types on this basis. Type A individuals have the A antigen, type B have the B, type AB have both, and type O have neither. The A and B antigens are complex oligosaccharides that differ in their terminal sugar. An H gene codes for a fucose transferase that adds a terminal fucose, forming the H antigen that is usually present in individuals of all blood types. Cardiovascular System | Blood Cardiovascular System | Blood Individuals who are type A also express a second transferase that catalyzes placement of a terminal N-acetylgalactosamine on the H antigen, whereas individuals who are type B express a transferase that places a terminal galactose. Individuals who are type AB have both transferases. Individuals who are type O have neither, so the H antigen persists. Antibodies against red cell agglutinogens are called agglutinins. Cardiovascular System | Blood Antigens very similar to A and B are common in intestinal bacteria and possibly in foods to which newborn individuals are exposed. Therefore, infants rapidly develop antibodies against the antigens not present in their own cells. Thus, type A individuals develop anti-B antibodies, type B individuals develop anti A antibodies, type O individuals develop both, and type AB individuals develop neither (Table 31–3). Cardiovascular System | Blood Table 31–3: Summary of ABO system. Plasma Blood Agglutinins in Frequency in Agglutinates Type Plasma United States % Red Cells of Type: O Anti-A, anti-B 45 A, B, AB A Anti-B 41 B, AB B Anti-A 10 A, AB AB None 4 None Cardiovascular System | Blood When the plasma of a type A individual is mixed with type B red cells, the anti-B antibodies cause the type B red cells to clump (agglutinate), as shown in Figure. The other agglutination reactions produced by mismatched plasma and red cells are summarized in Table 31–3. ABO blood typing is performed by mixing an individual’s red blood cells with antisera containing the various agglutinins on a slide and seeing whether agglutination occurs. Cardiovascular System | Blood Transfusion Reactions Cardiovascular System | Blood Transfusion Reactions: Dangerous hemolytic transfusion reactions occur when blood is transfused into an individual with an incompatible blood type; that is, an individual who has agglutinins against the red cells in the transfusion. The plasma in the transfusion is usually so diluted in the recipient that it rarely causes agglutination even when the titer of agglutinins against the recipient’s cells is high. Cardiovascular System | Blood However, when the recipient’s plasma has agglutinins against the donor’s red cells, the cells agglutinate and hemolyze. Free hemoglobin is liberated into the plasma. The severity of the resulting transfusion reaction may vary from an asymptomatic minor rise in the plasma bilirubin level to severe jaundice and renal tubular damage leading to anuria and death. Incompatibilities in the ABO blood group system are summarized in Table 31–3. Cardiovascular System | Blood Table 31–3: Summary of ABO system. Plasma Blood Agglutinins in Frequency in Agglutinates Type Plasma United States % Red Cells of Type: O Anti-A, anti-B 45 A, B, AB A Anti-B 41 B, AB B Anti-A 10 A, AB AB None 4 None Cardiovascular System | Blood Persons with type AB blood are “universal recipients” because they have no circulating agglutinins and can be given blood of any type without developing a transfusion reaction due to ABO incompatibility. Type O individuals are “universal donors” because they lack A and B antigens, and type O blood can be given to anyone without producing a transfusion reaction due to ABO incompatibility. Cardiovascular System | Blood This does not mean, however, that blood should ever be transfused without being cross-matched except in the most extreme emergencies, since the possibility of reactions or sensitization due to incompatibilities in systems other than ABO systems always exists. In cross-matching, donor red cells are mixed with recipient plasma on a slide and checked for agglutination. It is advisable to check the action of the donor’s plasma on the recipient cells in addition, even though, as noted above, this is rarely a source of trouble. Cardiovascular System | Blood Cardiovascular System | Blood A procedure that has recently become popular is to withdraw the patient’s own blood in advance of elective surgery and then infuse this blood back (autologous transfusion) if a transfusion is needed during the surgery. With iron treatment, 1000–1500 mL can be withdrawn over a 3- weeks period. The popularity of banking one’s own blood is primarily due to fear of transmission of infectious diseases by heterologous transfusions, but of course another advantage is elimination of the risk of transfusion reactions. Cardiovascular System | Blood The Rh Group Cardiovascular System | Blood The Rh Group: Aside from the antigens of the ABO system, those of the Rh system are of the greatest clinical importance. The Rh factor, named for the rhesus monkey because it was first studied using the blood of this animal, is a system composed primarily of the C, D, and E antigens, although it actually contains many more. Unlike the ABO antigens, the system has not been detected in tissues other than red cells. Cardiovascular System | Blood D is by far the most antigenic component, and the term Rh-positive as it is generally used means that the individual has agglutinogen D. The D protein is not glycosylated, and its function is unknown. The Rh-negative individual has no D antigen and forms the anti-D agglutinin when injected with D- positive cells. Cardiovascular System | Blood The Rh typing serum used in routine blood typing is anti-D serum. Eighty-five percent of whites are D-positive and 15% are D- negative; over 99% of Asians are D-positive. Unlike the antibodies of the ABO system, anti-D antibodies do not develop without exposure of a D negative individual to D- positive red cells by transfusion or entrance of fetal blood into the maternal circulation. Cardiovascular System | Blood However, D-negative individuals who have received a transfusion of D-positive blood (even years previously) can have appreciable anti-D titers and thus may develop transfusion reactions when transfused again with D-positive blood. Hemolytic Disease Of The Newborn Cardiovascular System | Blood Hemolytic Disease Of The Newborn: Another complication due to Rh incompatibility arises when an Rh-negative mother carries an Rh-positive fetus. Cardiovascular System | Blood Small amounts of fetal blood leak into the maternal circulation at the time of delivery, and some mothers develop significant titers of anti-Rh agglutinins during the postpartum period. During the next pregnancy, the mother’s agglutinins cross the placenta to the fetus. Cardiovascular System | Blood Cardiovascular System | Blood In addition, there are some cases of fetal-maternal hemorrhage during pregnancy, and sensitization can occur during pregnancy. In any case, when anti-Rh agglutinins cross the placenta to an Rh-positive fetus, they can cause hemolysis and various forms of hemolytic disease of the newborn (erythroblastosis fetalis). If hemolysis in the fetus is severe, the infant may die in utero or may develop anemia, severe jaundice, and edema (hydrops fetalis). Cardiovascular System | Blood Kernicterus, a neurologic syndrome in which unconjugated bilirubin is deposited in the basal ganglia, may also develop, especially if birth is complicated by a period of hypoxia. Bilirubin rarely penetrates the brain in adults, but it does in infants with erythroblastosis, possibly in part because the blood–brain barrier is more permeable in infancy. Cardiovascular System | Blood However, the main reasons that the concentration of unconjugated bilirubin is very high in this condition are that production is increased and the bilirubin-conjugating system is not yet mature. About 50% of Rh-negative individuals are sensitized (develop an anti-Rh titer) by transfusion of Rh- positive blood. Cardiovascular System | Blood Because sensitization of Rh-negative mothers by carrying an Rh-positive fetus generally occurs at birth, the first child is usually normal. However, hemolytic disease occurs in about 17% of the Rh-positive fetuses born to Rh-negative mothers who have previously been pregnant one or more times with Rh-positive fetuses. Cardiovascular System | Blood Fortunately, it is usually possible to prevent sensitization from occurring the first time by administering a single dose of anti-Rh antibodies in the form of Rh immune globulin during the postpartum period. Such passive immunization does not harm the mother and has been demonstrated to prevent active antibody formation by the mother. Cardiovascular System | Blood In obstetric clinics, the institution of such treatment on a routine basis to unsensitized Rh-negative women who have delivered an Rh-positive baby has reduced the overall incidence of hemolytic disease by more than 90%. In addition, fetal Rh typing with material obtained by amniocentesis or chorionic villus sampling is now possible, and treatment with a small dose of Rh immune serum will prevent sensitization during pregnancy. Plasma Cardiovascular System | Blood Plasma : The fluid portion of the blood contains 92% water and 8% solid , the plasma, is a remarkable solution containing an immense number of ions, inorganic molecules, and organic molecules that are in transit to various parts of the body or aid in the transport of other substances. Normal plasma volume is about 5% of body weight, or roughly 3500 mL in a 70- kg man. Cardiovascular System | Blood Plasma clots on standing, remaining fluid only if an anticoagulant is added. If whole blood is allowed to clot and the clot is removed, the remaining fluid is called serum. Serum has essentially the same composition as plasma, except that its fibrinogen and clotting factors II, V, and VIII have been removed and it has a higher serotonin content because of the breakdown of platelets during clotting. Cardiovascular System | Blood Plasma Proteins: Constitute 7% of the solid in the plasma ,the plasma proteins consist of albumin, globulin, and fibrinogen fractions. Most capillary walls are relatively impermeable to the proteins in plasma, and the proteins therefore exert an osmotic force of about 25 mm Hg across the capillary wall (oncotic pressure; that pulls water into the blood). Cardiovascular System | Blood The plasma proteins are also responsible for 15% of the buffering capacity of proteins in the blood (including hemoglobin ) because of the weak ionization of their substituent COOH and NH2 groups. At the normal plasma pH of 7.40, the proteins are mostly in the anionic. Cardiovascular System | Blood Plasma proteins may have specific functions (eg, antibodies and the proteins concerned with blood clotting), whereas others function as nonspecific carriers for various hormones, other solutes, and drugs. Circulating antibodies are manufactured by lymphocytes. Most of the other plasma proteins are synthesized in the liver. Hemostasis Cardiovascular System | Blood Hemostasis : Hemostasis is the process of forming clots in the walls of damaged blood vessels and preventing blood loss while maintaining blood in a fluid state within the vascular system. A collection of complex interrelated systemic mechanisms operates to maintain a balance between coagulation and anticoagulation Cardiovascular System | Blood Response To Injury: When a small blood vessel is transected or damaged, the injury initiates a series of events that lead to the formation of a clot. Cardiovascular System | Blood This seals off the damaged region and prevents further blood loss. The initial event is constriction of the vessel and formation of a temporary hemostatic plug of platelets that is triggered when platelets bind to collagen and aggregate. This is followed by conversion of the plug into the definitive clot. Cardiovascular System | Blood The constriction of an injured arteriole or small artery may be so marked that its lumen is obliterated, at least temporarily. The vasoconstriction is due to serotonin and other vasoconstrictors liberated from platelets that adhere to the walls of the damaged vessels. Cardiovascular System | Blood The Clotting Mechanism: The loose aggregation of platelets in the temporary plug is bound together and converted into the definitive clot by fibrin. Fibrin formation involves a cascade of enzymatic reactions and a series of numbered clotting factors. The fundamental reaction is conversion of the soluble plasma protein fibrinogen to insoluble fibrin. Cardiovascular System | Blood The process involves the release of two pairs of polypeptides from each fibrinogen molecule. The remaining portion, fibrin monomer, then polymerizes with other monomer molecules to form fibrin. The fibrin is initially a loose mesh of interlacing strands. It is converted by the formation of covalent cross-linkages to a dense, tight aggregate (stabilization). Cardiovascular System | Blood This latter reaction is catalyzed by activated factor XIII and requires Ca2+. The conversion of fibrinogen to fibrin is catalyzed by thrombin. Thrombin is a serine protease that is formed from its circulating precursor, prothrombin, by the action of activated factor X. It has additional actions, including activation of platelets, endothelial cells, and leukocytes via so-called proteinase activated receptors, which are G-protein–coupled. Factor X can be activated by either of two systems, known as intrinsic and extrinsic. Cardiovascular System | Blood Anti-clotting Mechanisms: The tendency of blood to clot is balanced in vivo by reactions that prevent clotting inside the blood vessels, break down any clots that do form, or both. These reactions include the interaction between the platelet-aggregating effect of thromboxane A2 and the antiaggregating effect of prostacyclin, which causes clots to form at the site when a blood vessel is injured but keeps the vessel lumen free of clot. Cardiovascular System | Blood Antithrombin III is a circulating protease inhibitor that binds to serine proteases in the coagulation system, blocking their activity as clotting factors. This binding is facilitated by heparin, a naturally occurring anticoagulant that is a mixture of sulfated polysaccharides. The clotting factors that are inhibited are the active forms of factors IX, X, XI, and XII. Cardiovascular System | Blood The endothelium of the blood vessels also plays an active role in preventing the extension of clots. All endothelial cells produce thrombomodulin, a thrombin- binding protein, on their surfaces. In circulating blood, thrombin is a procoagulant that activates factors V and VIII, but when it binds to thrombomodulin, it becomes an anticoagulant. Cardiovascular System | Blood Plasmin (fibrinolysin) is the active component of the plasminogen (fibrinolytic) system. This enzyme lyses fibrin and fibrinogen, with the production of fibrinogen degradation products (FDP) that inhibit Thrombin. Lymph Cardiovascular System | Blood Lymph: Lymph is tissue fluid that enters the lymphatic vessels. It drains into the venous blood via the thoracic and right lymphatic ducts. It contains clotting factors and clots on standing in vitro. In most locations, it also contains proteins that have traversed capillary walls and can then return to the blood via the lymph. Cardiovascular System | Blood Nevertheless, its protein content is generally lower than that of plasma, which contains about 7 g/dL, but lymph protein content varies with the region from which the lymph drains. Water insoluble fats are absorbed from the intestine into the lymphatics, and the lymph in the thoracic duct after a meal is milky because of its high fat content. Lymphocytes also enter the circulation principally through the lymphatics, and there are appreciable numbers of lymphocytes in thoracic duct lymph. Structural Features Of The Circulation Cardiovascular System | Blood Structural Features Of The Circulation: Here, the two major cell types that make up the blood vessels and how they are arranged into the various vessel types that subserve the needs of the circulation will be described. Cardiovascular System | Blood Endothelium: Located between the circulating blood and the media and adventitia of the blood vessels, the endothelial cells constitute a large and important organ. They respond to flow changes, stretch, a variety of circulating substances, and inflammatory mediators. They secrete growth regulators and vasoactive substances. Cardiovascular System | Blood Vascular Smooth Muscle: The smooth muscle in blood vessel walls has been one of the most- studied forms of visceral smooth muscle because of its importance in the regulation of blood pressure and hypertension. The membranes of the muscle cells contain various types of K+, Ca2+, and Cl− channels Cardiovascular System | Blood Contraction is produced primarily by the myosin light chain mechanism. However, vascular smooth muscle also undergoes prolonged contractions that determine vascular tone. These may be due in part to the latch bridge mechanism but other factors also play a role. In these cells, influx of Ca2+ via voltage-gated Ca2+ channels produces a diffuse increase in cytosolic Ca2+ that initiates contraction. Chapter Summary Cardiovascular System | Blood Chapter Summary: Blood consists of a suspension of red blood cells (erythrocytes), white blood cells, and platelets in a protein-rich fluid known as plasma. Blood cells arise in the bone marrow and are subject to regular renewal; the majority of plasma proteins are synthesized by the liver. Hemoglobin, stored in red blood cells, transports oxygen to peripheral tissues. Fetal hemoglobin is specialized to facilitate diffusion of oxygen from mother to fetus during development. Mutated forms of hemoglobin lead to red cell abnormalities and anemia. Cardiovascular System | Blood Complex oligosaccharide structures, specific to groups of individuals, form the basis of the ABO blood group system. AB blood group oligosaccharides, as well as other blood group molecules, can trigger the production of antibodies in naïve individuals following inappropriate transfusions, with potentially serious consequences due to erythrocyte agglutination. Cardiovascular System | Blood Blood flows from the heart to arteries and arterioles, thence to capillaries, and eventually to venules and veins and back to the heart. Each segment of the vasculature has specific contractile properties and regulatory mechanisms that subserve physiologic function. Physical principles of pressure, wall tension, and vessel caliber govern the flow of blood through each segment of the circulation. Cardiovascular System | Blood Transfer of oxygen and nutrients from the blood to tissues, as well as collection of metabolic wastes, occurs exclusively in the capillary beds. Fluid also leaves the circulation across the walls of capillaries. Some is reabsorbed; the remainder enters the lymphatic system, which eventually drains into the subclavian veins to return fluid to the bloodstream. Cardiovascular System | Blood Hypertension is an increase in mean blood pressure that is usually chronic and is common in humans. Hypertension can result in serious health consequences if left untreated. The majority of hypertension is of unknown cause, but several gene mutations underlie rare forms of the disease and are informative about mechanisms that control the dynamics of the circulatory system and its integration with other organs.