51. Anticoagulation system of blood: Five mechanisms keep platelet activation and the coagulation cascade in check. Abnormalities can lead to an increased tendency toward thrombosis: Protein C is a major physiological anticoagulant. It is a vitamin K-dependent serine protease enzyme that is activated by thrombin into activated protein C (APC). Protein C is activated in a sequence that starts with Protein C and thrombin binding to a cell surface protein thrombomodulin. Thrombomodulin binds these proteins in such a way that it activates Protein C. The activated form, along with protein S and a phospholipid as cofactors, degrades FVa and FVIIIa. Quantitative or qualitative deficiency of either may lead to thrombophilia (a tendency to develop thrombosis). Impaired action of Protein C (activated Protein C resistance), for example by having the "Leiden" variant of Factor V or high levels of FVIII also may lead to a thrombotic tendency. Antithrombin is a serine protease inhibitor (serpin) that degrades the serine proteases: thrombin, FIXa, FXa, FXIa, and FXIIa. It is constantly active, but its adhesion to these factors is increased by the presence of heparan sulfate (a glycosaminoglycan) or the administration of heparins (different heparinoids increase affinity to FXa, thrombin, or both). Quantitative or qualitative deficiency of antithrombin (inborn or acquired, e.g., in proteinuria) leads to thrombophilia. Tissue factor pathway inhibitor (TFPI) limits the action of tissue factor (TF). It also inhibits excessive TF-mediated activation of FIX and FX. Plasmin is generated by proteolytic cleavage of plasminogen, a plasma protein synthesized in the liver. This cleavage is catalyzed by tissue plasminogen activator (t-PA), which is synthesized and secreted by endothelium. Plasmin proteolytically cleaves fibrin into fibrin degradation products that inhibit excessive fibrin formation. Prostacyclin (PGI2) is released by endothelium and activates platelet Gs protein-linked receptors. This, in turn, activates adenylyl cyclase, which synthesizes cAMP. cAMP inhibits platelet activation by decreasing cytosolic levels of calcium and, by doing so, inhibits the release of granules that would lead to activation of additional platelets and the coagulation cascade.
52. Fibrinolysis is the process wherein a fibrin clot is broken down.Its main enzyme plasmin cuts the fibrin mesh at various places, leading to the production of circulating fragments that are cleared by other proteases or by the kidney and liver. Plasmin is produced in an inactive form, plasminogen, in the liver. Although plasminogen cannot cleave fibrin, it still has an affinity for it, and is incorporated into the clot when it is formed. Plasminogen contains secondary structure motifs known as kringles, which bind specifically to lysine and arginineresidues on fibrin(ogen). When converted from plasminogen into plasmin, it functions as a serine protease, cutting C-terminal to these lysine and arginine residues. Fibrin monomers, when polymerized, form protofibrils. These protofibrils contain two strands, anti-parallel, associated non-covalently. Within a single strand, the fibrin monomers are covalently linked through the actions of coagulation factor XIII. Thus, plasmin action on a clot initially creates nicks in the fibrin; further digestion leads to solubilization. Factors of fibrinolysis: Tissue plasminogen activator (t-PA)[3] and urokinase are the agents that convert plasminogen to the active plasmin, thus allowing fibrinolysis to occur. t-PA is released into the blood very slowly by the damaged endothelium of the blood vessels, such that, after several days (when the bleeding has stopped), the clot is broken down. This occurs because plasminogen became entrapped within the clot when it formed; as it is slowly activated, it breaks down the fibrin mesh. t-PA and urokinase are themselves inhibited by plasminogen activator inhibitor-1 and plasminogen activator inhibitor-2(PAI-1 and PAI-2). In contrast, plasmin further stimulates plasmin generation by producing more active forms of both tPA and urokinase. Alpha 2-antiplasmin and alpha 2-macroglobulin inactivate plasmin. Plasmin activity is also reduced by thrombin-activatable fibrinolysis inhibitor (TAFI), which modifies fibrin to make it more resistant to the tPA-mediated plasminogen More details: The removal of the clot is caused by plasmin cleavage of the fibrin monomers into soluble fibrin degradation products. Plasmin is formed by the cleavage of plasminogen between Arg561 and Val562. Plasmin is a two-chain trypsin-like serine protease. Plasminogen activator inhibitor 1 (PAI1) and plasminogen activator inhibitor 2 (PAI2) inhibit cleavage of plasminogen by tissue-type plasminogen activator (tPA) or urokinase plasminogen activator (uPA). The presence of fibrin fibers and fibrin degradation products [(DD)E1 and (DD)E2] exert a two-fold stimulation of tPA and uPA. Plasmin activity is also inhibited by alpha2-antiplasmin. Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxy-peptidase B-like proenzyme activated by the thrombin-thrombomodulin dimer. TAFI cleaves (DD)E2 to separate DD and E fragments which do not enhance the activation of tPA or uPA and results in a reduced feedback signal. Medicinal fibrinolytic related: Fibrinolytic drugs are given after a heart attack to dissolve the thrombus blocking the coronary artery. Antifibrinolytics, such as aminocaproic acid (ε-aminocaproic acid) and tranexamic acid are used as inhibitors of fibrinolysis. Their application may be beneficial in patients with hyperfibrinolysis because they arrest bleeding rapidly if the other components of the haemostatic system are not severely affected. This may help to avoid the use of blood products such as fresh frozen plasma with its associated risks of infections or anaphylactic reactions.
53. Immunoglobulin Structure: Antibodies are heavy globular plasma proteins, called glycoproteins.The variable parts of an antibody are its V regions, and the constant part is its C region.The Ig monomer is a "Y"-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chainsconnected by disulfide bonds. Each chain is composed of structural domains called immunoglobulin domains. These domains contain about 70-110 amino acids and are classified into different categories Heavy Chain: There are five types of mammalian Ig heavy chain denoted by the Greek letters. Each heavy chain has two regions, the constant region and the variable region. The constant region is identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. Heavy chains γ, α and δ have a constant region composed of three tandem (in a line) Igdomains, and a hinge region for added flexibility; heavy chains μ and ε have a constant region composed of four immunoglobulin domains.The variable region of the heavy chain differs in antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and is composed of a single Ig domain. Light Chain: there are two types of immunoglobulin light chain, which are called lambda (λ) and kappa (κ). A light chain has two successive domains: one constant domain and one variable domain. The approximate length of a light chain is 211 to 217 amino acids. Each antibody contains two light chains that are always identical; only one type of light chain, κ or λ, is present per antibody Special part: Some parts of an antibody have unique functions. The arms of the Y, for example, contain the sites that can bind two antigens (in general identical) and, therefore, recognize specific foreign objects. This region of the antibody is called the Fab (fragment, antigen binding) region. It is composed of one constant and one variable domain from each heavy and light chain of the antibody. The base of the Y plays a role in modulating immune cell activity. This region is called the Fc (Fragment, crystallizable) region, and is composed of two heavy chains that contribute two or three constant domains depending on the class of the antibody.[1] Thus, the Fc region ensures that each antibody generates an appropriate immune response for a given antigen, by binding to a specific class of Fc receptors, and other immune molecules, such as complement proteins. Function: Antibodies contribute to immunity in three ways: they prevent pathogens from entering or damaging cells by binding to them; they stimulate removal of pathogens by macrophages and other cells by coating the pathogen; and they trigger destruction of pathogens by stimulating other immune responses such as the complement pathway. Activation of complement: Antibodies that bind to surface antigens on a bacterium attract the first component of the complement cascade with their Fc region and initiate activation of the classical complement system. Activation of effector cells To combat pathogens that replicate outside cells, antibodies bind to pathogens to link them together, causing them to agglutinate. Since an antibody has at least two paratopes it can bind more than one antigen by binding identical epitopes carried on the surfaces of these antigens. By coating the pathogen, antibodies stimulate effector functions against the pathogen in cells that recognize their Fc region.The engagement of a particular antibody with the Fc receptor on a particular cell triggers an effector function of that cell; phagocytes will phagocytose, mast cells and neutrophils will degranulate, natural killer cells will release cytokines and cytotoxic molecules; that will ultimately result in destruction of the invading microbe Different class of Ig's: Immunoglobulin A (IgA) is an antibody that plays a critical role in mucosal immunity. More IgA is produced in mucosal linings than all other types of antibody combined;IgA has two subclasses (IgA1 and IgA2), IgA is a poor activator of the complement system, and opsonises only weakly. Its heavy chains are of the type α. Immunoglobulin D (IgD) is an antibody isotype that makes up about 1% of proteins in the plasma membranes of mature B-lymphocytes where it is usually coexpressed with another cell surface antibody. Immunoglobulin E (IgE) is a class of antibody (or immunoglobulin "isotype") that has been found only in mammals. IgE is a monomeric antibody with 4 Ig-like domains.It plays an important role in allergy, and is especially associated with type 1 hypersensitivity.IgE has also been implicated in immune system responses to most parasitic worms. Immunoglobulin G (IgG) are involved in predominantly the secondary immune response.The presence of specific IgG, in general, corresponds to maturation of the antibody response.IgG is the only isotype that can pass through the human placenta, thereby providing protection to thefetus in utero. Immunoglobulin M, IgM is the primary antibody against A and B antigens onred blood cells. IgM is by far the physically largest antibody in the human circulatory system. It is the first antibody to appear in response to initial exposure to antigen
54. Interferons (IFNs) are proteins made and released by lymphocytes in response to the presence of pathogens—such asviruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.
IFNs belong to the large class of glycoproteins known as cytokines. Interferons are named after their ability to "interfere" withviral replication within host cells. IFNs have other functions: they activate immune cells, such as natural killer cells andmacrophages; they increase recognition of infection or tumor cells by up-regulating antigen presentation to T lymphocytes; and they increase the ability of uninfected host cells to resist new infection by virus.
Interleukiny – grupa cytokin, czynników wzrostowych stymulujących podziały limfocytów. Wytwarzane przez makrofagi i limfocyty. Są czynnikiem wywołującym gorączkę.
Interleukiny, cytokiny, substancje o charakterze peptydów i białek wytwarzane przez wiele komórek biorących udział w odpowiedzi immunologicznej, a nie mających zdolności wiązania antygenu.
Interlukiny pełnią rolę mediatorów umożliwiających wzajemne oddziaływanie krwinek białych, stymulować ich namnażanie, różnicowanie i aktywność. Interleukiny produkowane przez limfocyty nazywane są limfokinami, natomiast produkowane przez makrofagi (należące dokomórek prezentujących antygen) – monokinami.
Interleukina 1 (IL-1) – silnie działający hormon tkankowy o charakterze polipeptydu, wydzielany przez makrofagi. IL-1 wpływa na limfocyty stymulując je i uwrażliwiając na kontakt z antygenem. Jest odpowiedzialna za podwyższenie temperatury ciała podczas procesów zapalnych (gorączka).
Interleukina 2 (IL-2) – mediator tkankowy o peptydowej budowie, wytwarzany przez limfocyty T helper (Th), stymulujący namnażanie i dojrzewanie limfocytów T.
A growth factor is a naturally occurring substance capable of stimulating cellular growth,[1] proliferation and cellular differentiation. Usually it is a protein or a steroidhormone. Growth factors are important for regulating a variety of cellular processes.
Growth factors typically act as signaling molecules between cells. Examples are cytokines and hormones that bind to specific receptors on the surface of their target cells.
Ex: Erythropoietin- a glycoprotein hormone that controls erythropoiesis, or red blood cell production. It is a cytokine forerythrocyte (red blood cell) precursors in the bone marrow.
Fibroblast growth factors - involved in angiogenesis, wound healing, and embryonic development. The FGFs are heparin-binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans have been shown to be essential for FGF signal transduction.
Thrombopoietin -is a glycoprotein hormone produced mainly by the liver and the kidney that regulates the production of plateletsby the bone marrow. It stimulates the production and differentiation of megakaryocytes, the bone marrow cells that fragment into large numbers of platelets.
55. Hemoglobin is the iron-containingoxygen-transport metalloprotein in the red blood cells of all vertebrates It is composed of 4 polypeptide chains. Each chain contains one heme group, each of which contains one iron ion. The iron is the site of oxygen binding; each iron can bind one O2 molecule thus each hemoglobin molecule is capable of binding a total to four (4) O2 molecules In the lungs, oxygen diffuses from alveolar air into the blood because the venous blood has a lower partial pressure. The oxygen dissolves in the blood. Only a small amount is carried as a physical solution (0.31 ml per 100 ml). The remainder of the oxygen is carried in chemical combination with the hemoglobin in red blood cells (erthrocytes). Hemoglobin (molecular weight of 68,000) is made from 4 hemes, a porphyrin ring containing iron and globin, a 4 protein chains. Oxygen is bound to the iron for the transport process. Hemoglobin (HHgb) behaves as a weak acid. If 2 is increased in the blood at the lungs, the equilibrium shifts to the right and H+ ions increase. Oxyhemoglobin can be caused to release oxygen by the addition of H+ ions at the cells. The difference in pH (7.44) of arterial blood and venous blood (pH = 7.35) is sufficient to cause release of oxygen from hemoglobin at the tissue cells. Variant forms that cause disease: Hemoglobin H (β4) - A variant form of hemoglobin, formed by a tetramer of β chains, which may be present in variants of αthalassemia. Hemoglobin Barts (γ4) - A variant form of hemoglobin, formed by a tetramer of γ chains, which may be present in variants of αthalassemia. Hemoglobin S (α2βS2) - A variant form of hemoglobin found in people with sickle cell disease. There is a variation in the β-chain gene, causing a change in the properties of hemoglobin, which results in sickling of red blood cells. Hemoglobin C (α2βC2) - Another variant due to a variation in the β-chain gene. This variant causes a mild chronic hemolytic anemia. Hemoglobin E (α2βE2) - Another variant due to a variation in the β-chain gene. This variant causes a mild chronic hemolytic anemia. Hemoglobin AS - A heterozygous form causing Sickle cell trait with one adult gene and one sickle cell disease gene Hemoglobin SC disease - Another heterozygous form with one sickle gene and another encoding Hemoglobin C.
56. Buffer System of blood. The bicarbonate buffering system is an important buffer system in the acid-base homeostasis of living things, including humans. As a buffer, it tends to maintain a relatively constantplasma pH and counteract any force that would alter it. In this system, carbon dioxide (CO2) combines with water to form carbonic acid (H2CO3), which in turn rapidly dissociates to form hydrogen ion and bicarbonate (HCO3- ) according to the reaction below. The reaction is catalyzed by the enzyme carbonic anhydrase. Any disturbance of the system will be compensated by a shift in the chemical equilibrium according to Le Chatelier's principle. For example, if the blood gained excess hydrogen ions (a process called acidosis), some of those hydrogen ions would shift to carbon dioxide, minimizing the increased acidity. This buffering system becomes an even more powerful regulator of acid-base homeostasis when it is coupled with the body's capacity for respiratory compensation, in which breathing is altered to modify the amount of CO2 in circulation. In the above example, the body could increase breathing (respiratory alkalosis) to expel the excess CO2, pulling still more hydrogen ions toward the production of carbon dioxide. The process could continue until the excess acid is all exhaled. This process is extremely important in human physiology. It manages the many acid and base imbalances that can be produced by both normal and abnormal physiology. It also affects the handling of carbon dioxide as it is constantly produced as a waste product of cellular respiration when cells make energy. Acid-base imbalance is an abnormality of the human body's normal balance of acids and bases that causes the plasma pH to deviate out of the normal range (7.35 to 7.45). In the fetus, the normal range differs based on which umbilical vessel is sampled (umbilical vein pH is normally 7.25 to 7.45; umbilical artery pH is normally 7.18 to 7.38).It can exist in varying levels of severity, some life-threatening.There are four basic processes: metabolic acidosis, respiratory acidosis, metabolic alkalosis, and respiratory alkalosis. Metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low (less than 7.35) due to increased production of hydrogen by the body or the inability of the body to form bicarbonate (HCO3-) in the kidney. Its causes are diverse, and its consequences can be serious, including coma and death. Respiratory acidosis is a medical condition in which decreased respiration (hypoventilation) causes increased blood carbon dioxide and decreased pH. Metabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range ( 7.35-7.45 ). This is usually the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations.These can be divided into two categories, depending upon urine chloride levels Respiratory alkalosis is a medical condition in which increased respiration (hyperventilation) elevates the blood pH.causes psychiatric causes: anxiety, hysteria and stress CNS causes: stroke, subarachnoid haemorrhage, meningitis drug use: doxapram, aspirin, caffeine and coffee abuse moving into high altitude areas, where the low atmospheric pressure of oxygen stimulates increased ventilation lung disease such as pneumonia, where a hypoxic drive governs breathing more than CO2 levels (the normal determinant) fever, which stimulates the respiratory centre in the brainstem pregnancy high levels of NH4+ leading to brain swelling and decreased blood flow to the brain sexual activity, which may induce excessive breathing due to excitation.
57. Composition of blood: The average adult has a blood volume of roughly 5 liters (1.3 gal), composed of plasma and several kinds of cells (occasionally called corpuscles); these formed elements of the blood are erythrocytes (red blood cells, RBCs), leukocytes (white blood cells), and thrombocytes (platelets). By volume, the red blood cells constitute about 45% of whole blood, the plasma about 54.3%, and white cells about 0.7%. Cells One microliter of blood contains: 4.7 to 6.1 million (male)erythrocytes: In most mammals, mature red blood cells lack a nucleus and organelles. They contain the blood's hemoglobin and distribute oxygen. The red blood cells (together with endothelial vessel cells and other cells) are also marked by glycoproteins that define the different blood types. The proportion of blood occupied by red blood cells is referred to as the hematocrit, and is normally about 45%. The combined surface area of all red blood cells of the human body would be roughly 2,000 times as great as the body's exterior surface. 4,000–11,000 leukocytes:White blood cells are part of the immune system; they destroy and remove old or aberrant cells and cellular debris, as well as attack infectious agents (pathogens) and foreign substances. The cancer of leukocytes is called leukemia. 200,000–500,000 thrombocytes: also called platelets, are responsible for blood clotting (coagulation). They change fibrinogen into fibrin. This fibrin creates a mesh onto which red blood cells collect and clot, which then stops more blood from leaving the body and also helps to prevent bacteria from entering the body. Plasma About 55% of whole blood is blood plasma, a fluid that is the blood's liquid medium, which by itself is straw-yellow in color. The blood plasma volume totals of 2.7–3.0 liters (2.8–3.2 quarts) in an average human. It is essentially an aqueous solution containing 92% water, 8% blood plasma proteins, and trace amounts of other materials. Plasma circulates dissolved nutrients, such as glucose, amino acids, and fatty acids (dissolved in the blood or bound to plasma proteins), and removes waste products, such as carbon dioxide, urea, and lactic acid. Other important components include: Serum albumin Blood-clotting factors (to facilitate coagulation) Immunoglobulins (antibodies) lipoprotein particles Various other proteins Various electrolytes (mainly sodium and chloride) The term serum refers to plasma from which the clotting proteins have been removed. Most of the proteins remaining are albumin and immunoglobulins. Blood protein: Blood proteins, also called serum 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. Separating serum proteins by electrophoresis is a valuable diagnostic tool as well as a way to monitor clinical progress. Often mentioned blood proteins: Albumin -create oncotic pressure and transports other molecules immunoglobulinsn -participate in immune system Fibrinogens- blood coagulation alpha 1-antitrypsin -neutralize trypsin that has leaked from the digestive system Regulatory proteins Regulation of gene expression Other types of blood proteins include: Prealbumin Alpha 1 antitrypsin Alpha 1 acid glycoprotein Alpha 1 fetoprotein Haptoglobin Alpha 2 macroglobulin Ceruloplasmin Transferring C3/C4 Beta 2 microglobulin Beta lipoprotein Gamma globulin proteins C-reactive protein (CRP) alpha2-macroglobulin Other globulins, which are of three types- alpha, beta and gamma. Lipoproteins (chylomicrons, VLDL, LDL, HDL) Transferrin Prothrombin MBL or MBP All the plasma proteins are synthesized in liver except gamma globulins.
58. Enzymes of blood plasma: Enzymes Enzymes are the biological catalysts of the body responsible for regulating every chemical process that takes place. The body contains 75,000 different enzyme materials, with each one assigned to a specific chemical process. These materials are made out of protein molecules that are designed to initiate chemical reactions between cells and cell structures. In effect, these materials are present in every area of the body which is why blood samples can provide vital information on the body's enzyme activity. Blood Testing (Enzymodiagnostic) Blood enzyme test results act as a miniature snapshot of the body's chemical processes. Normal test results indicate that the body's organs and system processes are functioning as they should. Major body processes involving heart, liver and kidney function utilize large amounts of enzyme materials. Normal blood test results will show a certain level of each enzyme within a profile. The amount of an enzyme within a blood sample serves as a "marker," meaning it provides an indication of whether or not a condition or disorder is developing within the body. Kidneys There are three main kidney enzymes present within a blood test panel: BUN, creatinine and uric acid. Normal test results for BUN, or blood urea nitrogen, will fall within a range of 7 to 18 deciliters (dL). Normal creatinine levels will range between 0.6 to 1.2 dL. Results for uric acid will show a reading between 3 and 8.2 dL. When readings come back above or below these norms, infection, kidney disease or excess protein in the diet are some of the possible conditions present in the body. Liver Blood testing is one of the most common diagnostic tools used to screen for liver function. If the liver has sustained some sort of damage, its tissue will begin to break down. When this happens the enzymes contained in the tissue will enter the bloodstream. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) are the primary liver enzymes. Normal test results will show AST and ALP levels between 8 to 20 dL, while ALP readings will come in at 90 to 239 dL Heart Blood enzyme levels are used as a way to determine heart function, as well as any damage the heart may have sustained after a heart attack. As in the case of liver tissue, heart tissue releases enzymes into the bloodstream when damage has occurred. Creative kinase (CK) is an enzyme contained in the heart muscle. Normal test results for CK will fall below 174 dL in men and 140 dL or lower in women. Gamma glutamyl transferase (GGT) is another prominent heart enzyme that also serves as a marker for kidney function. Normal GGT test results will range between 8 and 37 dL for men under 45 years of age and 5 to 24 dL for women under 45 years of age. The range for females who are 45 years or older changes to 6 to 37 dL as hormonal changes begin to effect different processes within the body.
59. Kallicrein-Kinnin System system is plays a role in inflammation, blood pressure control, coagulation and pain. Its important mediators bradykinin and kallidin are vasodilators and act on many cell types. The system consists of a number of large proteins, some small polypeptides and a group of enzymes that activate and deactivate the compounds. Proteins High-molecular weight kininogen (HMWK) and low-molecular weight kininogen (LMWK) are precursors of the polypeptides. They have no activity of themselves. HMWK is produced by the liver together with prekallikrein (see below). It acts mainly as a cofactor on coagulation and inflammation, and has no intrinsic catalytic activity. LMWK is produced locally by numerous tissues, and secreted together with tissue kallikrein. Polypeptides Bradykinin (BK), which acts on the B2 receptor and slightly on B1, is produced when kallikrein releases it from HMWK. It is a nonapeptide with the amino acid sequence Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg. Kallidin (KD) is released from LMWK by tissue kallikrein. It is a decapeptide. KD has the same amino acid sequence as Bradykinin with the addition of a Lysine at the N-Terminus, thus is sometimes referred to as Lys-Bradykinin. Enzymes Kallikreins (tissue and plasma kallikrein) are serine proteases that liberate kinins (BK and KD) from the kininogens, which are plasma proteins that are converted into vasoactive peptides.Prekallikrein is the precursor of plasma kallikrein. It can only activate kinins after being activated itself by factor XIIa or other stimuli. Carboxypeptidases are present in two forms: N circulates and M is membrane-bound. They remove arginine residues at the carboxy-terminus of BK and KD. Angiotensin converting enzyme (ACE), also termed kininase II, inactivates a number of peptide mediators, including bradykinin. It is better known for activating angiotensin. Neutral endopeptidase also deactivates kinins and other mediators. Pharmacological antagonist of kinine: Inhibition of ACE with ACE inhibitors leads to decreased conversion of angiotensin I to angiotensin II (a vasoconstrictor) but also to an increase in bradykinin due to decreased degradation. This explains why some patients of ACEi's develop a dry cough, and some react with angioedema, a dangerous swelling of the head and neck region. There are hypotheses that many of the ACE-inhibitors' beneficial effects are due to their influence on the kinin-kallikrein system. This includes their effects in arterial hypertension, inventricular remodeling (after myocardial infarction) and possibly diabetic nephropathy.
60. Nonorganics components of blood blasma: Inorganic components of blood plasma are the usual electrolyte such as: chlorides, carbonates, bicarbonates, sulfates phosphates of sodium potassium calcium magnesium iron etc sodium chloride (predominant) Inorganic salts of blood plasma = 1-2% of total volume.
· cations - most of the sodium and potassium ions
· anions - chloride ions are the most numerous and carbonate
The content of inorganic constituents in the tissue fluid is similar to their proportion in the plasma. Of particular importance is the ratio of sodium to potassium, which affectscell excitability, and thus the properties of the cell membrane and cellular metabolism