Blood and its defence functions. Oral cavity role in the blood defence function regulation. 


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Blood and its defence functions. Oral cavity role in the blood defence function regulation.



Blood is the body’s principal extracellular fluid, ensuring the various physiological functions. As the humoral link blood participates in all organism constants stabilizing and provides homeostasis – the constant state of its inner medium. Blood is characterized by presence of a great variety of fixed qualitative features – constants. There are two principal groups of such constants: flexible and solid ones. Flexible constants may vary in wide ranges not leading to the serious changes of life activity. These constants include circulating blood volume, formed elements number, plasma and formed elements correlation (haematocrit), haemoglobin concentration, specific weight, blood viscosity, blood sedimentation velocity (BSV). Solid constants include such ones the deviation of which even in small amounts leads to life activity down-regulation. This constants group contains ion blood composition, pH, osmotic pressure, protein plasma composition etc.

Circulating blood, haematopoiesis organs, blood destruction organs and regulation organs belong to blood system.

Main blood functions are: thetransport, the defense, the regulative ones. Transport blood function – ensures nutrition and respiration. Dring its course through the tissue capillaries blood delivers nutrients from the small intesatine and oxygen from the lungs to the cells. It also removes the toxic waste products of cellular metabolism (metabolites), such as urea and carbon dioxide, from the tissue environment and eliminates them as it circulates through the kidneys and lungs respectively. Defense blood function – theimmunity,thephagocytosis,thecomplement system, the haemostasis, the fibrinolysis, the antioxidative and some others. Regulative blood function includes the participating in the humoral (the hormones, the mediators and other bioactive substances) and in the physio-chemical regulation (the temperature, the osmotic pressure, the acid-alkaline balance and etc.).

Some defense blood reactions are connected with the erythrocytes. They produce the antitoxins, take part in blood coagulation and fibrinolysis either.

The main white blood cell function is to participate in defense organism reactions against foreign agents. There exist the natural (nonspecific) and specific defence forms.

The nonspecific defence is directed to eliminating any foreign agent. The phagocytosis, the complement system and others humoral defense factors are the main types of such reactions. Phagocytosis consists of engulfing the microbes and cells via the formation of the pseudopods followed by endocytosis of the phagocytic vesicle. Next, the endocytotic vesicle is incorporated into the lysosomes of the phagocytes where the microbes and cells are digested by lysosomal enzymes.Thisphenomenon is adequate the neutrophiles, monocytes, eosinophiles, macrophages and thrombocytes. In the course of the phagocytosis process we differentiate such stages as the phagocyte approaching to the phagocytized object (or ligand), the ligand contact with the phagocyte membrane, the ligand engulfing, digestion and destruction of the phagocytized object. The phagocytes find their way to the site of injury by chemotaxis or similar guiding mechanisms.

Complement system -is a special enzyme system consisting of the proteins (more than 20 types). In includes 9 components (C1…C9). During the activation process some of its components are cleaved in the fragments influencing directly the course of specific and nonspecific defense reactions. There exist the classical and alternative ways of complement system activation. The destruction of foreign and old cells, the phagocytosis and the immune reactions course activates, the vessel wall permeability increases, the blood coagulation fastens at the complement system activation that influence the pathological process.

The other humoral defense factors – defense reactions connected with the action of such substances as lysozyme and interferon. Lysozyme as a protein possesses the enzyme activity suppressing the growth and the development of causative agents and destroying some of the microorganisms. It can be found in nasal mucosa, intestines, salivary secret, lacrimal fluid etc. In small amounts one can find it in the granules of polymorphonuclear leukocytes, in macrophages and when destroyed they fall into the extracellular fluid. Interferon as the globulin of blood plasma can be located in the lymphocytes providing antiviral defense and delaying the cancer cell growth.

Specific defense – immunity – is a reaction complex directed to maintaining the homeostasis on meeting the host’s body with the antigens which are considered as foreign (despite their forming in the organism itself or if they come into it from outside). Under the action of antigen the host body forms the antibodies, activates lymphocytes and thus they get the ability to participate in the immune response. This antigen ability to cause the specific immune response is due to the presence of multiple determinants on its molecule. The active centers of forming antibodies specifically correspond to the determinants like the key to the lock. The antigen interacting with its corresponding antigen forms the immune complex.

The immune organs are devided into central (thymus, bursa of Fabricius, bone marrow) and the peripheral (lymphatical nodes, spleen etc.). There are two categories of acquired immune responces – humoral or antibody-mediated and cell-mediated.

In addition to the above mentioned information we can say that not only the nervous and humoral regulation of various organism functions but the immunological one exist in the human body. Thus, the lymphokines and monokines secreted by the lymphocytes, the monocytes and the macrophages are capable of changing the central nervous system, the heart, the vessels, the respiratory and digestive organs action. As for the interleukines they are involved in all the physiological body reactions. The immune system itself is not only the defense system (especially the antiinfectious) but the important regulative system too. Functionally it is tied with both nervous and the endocrine organism system. Such an approach to functioning of this system not only extends our data about its activity but permits to outline the new therapy ways of acquired and hereditary disorders.

The defence blood function is closely associated with the platelets (thrombocytes). They have the phagocyte activity, contain the immunoglobulins, are the source of the lysozyme and cytokines, necessary for the reparation processes. But one of their major functions is to participate in the haemostasis.

Because blood flows continuously in the vascular bed, it is prone to leave the body quickly whenever there is either an external or internal injury to the tissues. The vital importance of blood to tissue survival has produced a variety of preventive and defensive mechanisms aimed at minimizing blood loss during injury.

Haemostasis – is the reactions complex aimed at the blood loss stoppage. In fact the significance of haemostasis system is much more complicated and far exeeds the limits of fighting with blood loss.

The main tasks of the haemostasis are the following: the fluid blood state storage, the transcapillary exchange, the vessel wall resistence regulation and the influence the reparation processes and so on.

They distinguish the vessel-platelet haemostasis and blood coagulation (clotting). Speaking about the first case the question is about the blood loss stoppage from the small vessels with low blood pressure; the second one is connected with the blood loss fighting at the arteries and veins rupture. Such division is rather conditional as both at small and large vessels rupture along with the thrombocyte plug forming the blood coagulation is occured. On the other hand such a division is very suitable for clinical practice because at the vessel-platelet haemostasis disorders the finger skin puncture (or the ear lobe) is accompanied by prolonged coagulation time whereas the bleeding time remains normal (for example at haemophilia because of normal platelet count in hemophiliac). Haemophilia is a wide-spread hereditary pathological state. It is the excessive bleeding caused by a congenital lack of a substance (plasma coagulation factor VIII, IX, X or XI) necessary for blood clotting. Treatment consists of administration of the deficient factor.

Vessel-platelet haemostasis comes to the platelet plug (or thrombus) forming. Conditionally it is devided into three stages. The first stage is temporary (primary and secondary) vasoconstriction - immediately in a few seconds after the injury the primary vasoconstriction occurs due to it the bleeding at the first moment may not happen or bears the limited character. It is caused by the adrenaline or norepinephrine releasing in response to the pain irritation and lasts for about 10-15 sec. Futher, the secondary vasoconstriction occurs because of the platelet activation and the releasing from them in a blood the vasoactive substances - serotonine, adrenaline, thromboxanes.

The second stage is the platelet plug forming because of the adhesion (the binding to the foreign surface) and the aggregation (clumping of the platelets). The adhesion takes place immediately after the injury to the collagen and other adhesion subendothelium proteins. It occurs because of the glycoproteins action by means of which the platelets clump to the collagen fibres and by means of the Willebrand factor as well that using one of its active centers is bound up to the platelet receptor and the other of its receptors to the collagen or subendothelium. From the adhesive platelets and the injured endothelium as well the ADP (adenosine diphosphate) is released, which is one of the major factors of platelet aggregation. Under the unfluence of ADP the platelets clump, so forming the aggregates. This reaction increasing is due to the platelet activation factor (PAF), thrombin and adrenaline. On this stage the aggregation is reversible and the desaggregation may happen. To complete the platelet plug forming a number of additional mechanisms (they mainly are associated with the platelets) are required. When the sygnal comes into the platelets the calcium content increases in them and the phospholipase A2 activation occurs. The latter one leads to the arachidonic acid releasing from the platelets membranes that further converts into the very active prostaglandines and thromboxanes. When removing from the platelets they make the aggregation irreversible. As a result the platelet plug or thrombus is formed. But at first it is capable of passing the blood as it is loose. After releasing the actomyosine (thrombostenine) from the platelets during their aggregation the platelet plug is shortened and reinforced. This is the third stage of the vessel-platelet haemostasis – the platelet plug retraction.

Under the normal condition the blood loss stoppage from small vessels lasts from 2 to 4 minutes. Such index in the clinic is known as the bleeding time.

The arachidonic acid derivates – prostacyclin and thromboxane A2 - play a very important role in the vessel-platelet haemostasis regulation. Prostacyclin is produced by endotheliocytes under the enzyme prostacyclinsynthetase influence. Under the physiological conditions prostacyclin predominates over thromboxane – powerful platelet proaggregant. At any endothelium injury in the trauma place the prostacyclin producing disturbs and the thromboxane action begins to predominate. Thus, the favourable conditions for the platelet aggregation emerge. Some vitamins (A,C,E) and foods (onion, garlic) are the platelet aggregation inhibitors.

Blood coagulation is an enzyme process where both the plasmic and the cell factors participate. Most of the haemocoagulation plasma factors are the proenzymes and their activation occurs due to the limited protheolysis and is accompanied by the peptide inhibitors cleavage. They are designated with the Roman figures. There are 13 such factors in plasma.

The platelets have an important role in a blood coagulation process. They contain a lot of (more than 30) different substances which deal with the haemostasis process. Some of them (according to the various literature scientific sources from 5 to 15) are called the platelet (thrombocyte) coagulation factors that are designated the Ciphers.

In the erythrocytes one can found a number of substances like the platelet ones. They are known as the erythrocyte blood coagulation factors. They have no figure designation. The leukocytes have the coagulation factors called leukocyte factors. For example, monocytes and macrophages upon antigen stimulating synthesize the protein thromboplastine part namely apoprotein III (tissue factor).

Tisue factors the main component of which is thromboplastine play a significant role in a blood coagulation. Thromboplastine or tissue factor consists of the protein part apoprotein III and the phospholipid complex and it is often considered to be a cell membrane fragment. Upon the tissue destruction or endothelium stimulation by means of proinflammatory cytokines or endotoxin the tissue factor can be released in a blood circulation. In various blood circulation regions in the vessels its content differs (e.g. in veins and arteries, lower or upper extremities, on the right or on the left in ones of the same name).

The blood coagulation process may be divided into 3 phases. The first one includes the complex of consequent reactions leading to the prothrombinase forming. The prothrombinase forming can be realized via two ways: extrinsic (from injured tissue) or intrinsic (from blood). The extrinsic way of the prothrombinase forming provides the obligatory presence of the thromboplastine (or Factor III, tissue factor). The prothrombinase forming via the extrinsic way begins with the factor VII activation by the interaction with the thromboplastine. In its turn, the factor VII transforms the factor X into the active state. Futher the factor Xa activates the factor V. The factors III+IV+ Xa +Va form the complex compound named the prothrombinase. Via the extrinsic way the prothrombinase is synthesized very quickly (it takes the seconds!).

The factor XII (the contact factor) is an important initiator of the intrinsic prothrombinase forming way. The kallikrein and high – molecular kininogen (HMK) are the participants of this reaction. The contact factor is activated by any injured surface, skin, the collagen, the adrenaline and transforms the factor XI in its active state. The XIa influences directly the factor IX, transforming it into the factor IXa. Its specific activity is directed to the factor X protheolysis (converting it into its active form) and occurs on the platelet phospholipid surface at the necessary factor VIII participating. The whole factor complex on the phospholipid platelet surface received its name as the thenase (the thenase complex). As it was mentioned above, the kallikrein and high – molecular kininogen (HMK) are the participants in a blood coagulation process by means of which the extrinsic and intrinsic ways combination takes place. The intrinsic pathway is more prolonged in time (up to 5-6 minutes) as it is accomplished with a great number of different blood coagulation factors. It is also implemented without vessel wall injuring (e.g. at the adrenaline concentration increasing that activates the factor XII).

The second phase of blood coagulation is a transition of prothrombine to thrombine which is performed by the prothrombinase. It is a protheolytic prothrombine cleavage resulting in the enzyme thrombine presence. This enzyme possesses the coagulative activity. It takes only several seconds.

The third phase of blood coagulation is a fibrinogen transition to fibrin. At first under the influence of the thrombine two fibrinopeptides A and two fibrinopeptides B are released. As a result of it the fibrin-monomer is formed. Futher, the soluble fibrin is formed due to the polimerization process. But because of the XIII factor (fibrinase) activation its transition into the insoluble fibrin (fibrin-polymer) is taking place. Next, this fibrin plug is reinforced thanks to the platelets action (they release the protein thrombosthenin). This process is known as a retraction. The plug in its turn is named a clot. The fibrin net becomes gradually tight. That’s why the clot causes the vessel occlusion and the bleeding is ceased.

Inspite of circulation there are all necessary factors for the clot forming. Under physiological conditions in presence of uninjured vessels a blood remains fluid. It’s determined by the presence of components, preventing the blood coagulation (anticoagulants) in the circulation. Besides, a blood is kept fluid because of the haemostatic system fibrinolytic components in it.

The natural anticoagulants are devided into primary and secondary ones. The primary anticoagulants are such substances that are constantly present in the circulation. They may be of three groups: antithromboplastines, antithrombines and fibrin forming inhibitors. Otherwise, all these anticoagulants are the substances that act depending on the blood coagulation process stage.

The substances preventing the prothrombinase forming are the antithromboplastines (they are secreted by the vessel wall endothelium, their content in veins is larger than in arteries), vitamin K-dependent protein C (inhibits the factors V, VIII), protein S, the endothelium protein – thrombomodullin, the placenta anticoagulant protein and others.

 

The substances inhibiting thrombine action are antithrombines. They are of different groups but the most important of them are: antithrombin III and heparin. Antithrombin III – is a prothein of a globulin origin that is formed in liver, kidneys, spleen, lungs and blood vessels as well. Its content reduces with the age, its concentration is less in women as compared with men (NB! Women have the thrombophlebitis and phlebothromboses more often than men), its content in pregnants gets smaller. Its content is smaller in human beings with the II(A) blood group and the people eating fat food (particularly of animal origin). Its activity decreases at the diseases of those organs where it is formed. Antithrombine III is a heparin cofactor. Besides, it inhibits up to 70 per cent of thrombine occuring in blood as well as the factors IXa, Xa, XIa, XIIa. There are cases of its hereditary insufficiency.

Heparin – is also an antithrombine. It is a polysaccharide transforming antithrombine III in anticoagulant of immediate action thus increasing its activity. In absence of antithrombine III heparin possesses a weak anticoagulant activity. Moreover, heparin without antithrombine III doesn’t prevent the external prothrombinase forming way. So, heparin efffect may be very weak as a result of antithrombine level decreasing in patients’ blood that it’s necessary to take into account at its administration. Heparin also forms the complex combinations with thrombogenic protheins and hormones which finally possess anticoagulant and fibrinolytic features. Heparin influences the thrombocyte aggregation, has antiviral action and antiinflammatory properties as well. In blood heparin can be found in basophiles, in vessels – in mast cells. It it degenerated by the heparinase enzyme in liver.

Secondary anticoagulants – are the “worked-off” blood coagulation factors (that participated in blood coagulation process) and degradation fibrin and fibrinogen products or derivates (PDF) having antiaggregative and anticoagulative action. The secondary anticoagulants role comes to limiting of intravascular blood coagulation and thrombus dissemination via vessels.

At various diseases there may appear the pathological anticoagulants dealing with different immunoglobuline classes and inactivating separate blood coagulation factors.

Fibrinolysis – is an integral part of haemostasis system. It always accompanies the process of blood coagulation and even is activated by the same factors (XIIa, kallylrein, HМК and others). Being the important defence reaction it prevents the occlusion of blood vessels by fibrin clots and leads to the vessel recanalization after the bleeding stoppage. The fibrinolysis components play key role in removing of extracellular matrix. Besides, they regulate the growth and the division of cells, the reparation of wounds, the regeneration of muscles, the growth and metastasis of tumors etc.

The main enzyme destroying the fibrin is plasmin (sometimes it is called fibrinolysin), that in a circulation is in non-active state as proenzyme plasminogen. Under the influence of the activators there occurs the cleavage of peptide junctions of plasminogen that leads to in it’s turn to plasmin forming. Plasminogen may be found not only in plasma and in serum but in other types of liquids (sperm, follicules, saliva), in tissues and leukocytes either. This is a prothein of a globulin origin the biosynthesis of which is performed in a bone-marrow.

To transform into plasmin plasminogen needs to be activated. Plasminogen activators -are contained first of all in tissues (vessel wall). Tissue plasminogen activator (TPA) – is mainly formed in vessel wall endothelium. Urokinase as plasminogen activator is produced in kidneys (juxtaglomerular apparatus), in fibroblastes, epitheliocytes, pneumocytes, placenta, endotheliocytes either. There are also plasminogen actovators in erythrocytes, thrombocytes and leukocytes.

Except plasminogen activators there exist the fibrinolysis inhibitors in plasma.

Fibrinolytic blood activity is greatly determined by the correlation between the fibrinolysis activators and inhibitors.

Fibrinolysis like the blood coagulation process is performed in three phases. The first phase, the forming and secreting of plasminogen activators may occur in extrinsic and intrinsic ways. The extrinsic way of plasminogen activation is due to the TAP, urokinase and some others. The intrinsic way of plasminogen activation is divided into Hageman-dependent and Hageman-independent. The first of them takes place under the influence of the XIIa, kallylrein and HMK factors that transform plasminogen into plasmin. Hageman-dependent fibrinolysis is accomplished very fast and bares urgent character. Its main designation cimes to the circulation clearence from fibrin clots forming in course of disseminated intravascular blood coagulation process. The second one can be realized under the influence of proteins “C” and “S”.

In the second fibrinolysis stage under the action of the activators mentioned above plasminogen transforms into plasmin. Finally, in the third stage, plasmin effects on fibrin. As a result at first the early (high-molecular) and then the late (low-molecular) fibrin degradation products or derivates (PDF) appear. The early PDF influence the platelet aggregation and blood coagulation thus increasing them. The late PDF are characterized by the anticoagulant features and effort the fibrinolysis reaction.

The oral cavity role in the defence blood functions regulation. Pathological conditions in different regions of oral cavity in particular often oral mucosa are the primary signs of haemopoietic system injury that makes the patients consult the dentist. While examining such patients the dentist must pay attention to the oral mucosa colour, gingivae, tongue, tonsils condition. On the mucosa may happen multiplied and different-sized haemorrhagies. Such signs are non-specific because they are not the distinguishing features of separate blood diseases but they point out to the latent pathological process in human organism. In these cases the clinic examination of dental patients required additional laboratory investigations among which the clinic-physiological blood analysis is of great importance. Such knowledge will help to determine the volume and the type of permitted and necessary doctors’ interfearence at the treatment of any dental patient.

What role does the oral cavity play in a regulation of blood protective functions? The special value in an oral cavity protective functions have the antibodies. There is a secretory immunoglobulin "А" (SigA) in an oral liquid. Its contents in a saliva is much higher than in serum. It is synthesized locally by plasma cells formed from B - lymphocytes, mainly, in a submucosal layer. It interferes with antigenes introduction, has antibacterial and virusneutralizing activity. The persons with defect of the given immunoglobulin have often inflammatory diseases of an oral cavity. In a saliva there are the components of a complement (С3, С4), playing the important role in the phagocytosis reactions and also stimulating the cell and humoral immunity reactions. They get in a saliva from circulation through odontogingival sulcus.

Phagocytosis also plays an important role in an oral cavity. For one day from a gingival blood 1/80 of all blood leucocytes is allocated in an oral cavity. At inflammations this digit is enlarged at 2-10 times. There is a leukocytic formula of a saliva. 95-97 % of it make neutrophils, 1-2 % - lymphocytes and 2-3 % - monocytes.

The oral mucosal epithelium serves as a barrier on the way of any antigenes penetration, including cancerogenes. The appreciable amount of neutrophils, and also monocytes is located under an epithelium, through which they migrate from the vessels of an own plate in a gingival sulcus break. Neutrophils migration velocity makes 30 000 in 1 minute. In oral mucosal epithelium one can find out Т-lymphocytes and B- lymphocytes. An important role in maintenance of oral mucosal epithelium barrier function play Langerhans’ cells, amounting about 2 % of cell population. They, mainly, are in a status of constant movement, that facilitates a meeting with an antigene. There are dendrite antigene-presenting cells, epitheliocytes and others in oral mucosal epithelium.

The oral cavity plays an important role in haemostasis regulation as well. Saliva contains a substance resembling of a tissue thromboplastin properties. It contains in a great number especially in the mixed saliva containing blood cell and desquamated epithelium. However, parotid saliva, as well as centrifugated and released from cells oral liquid, also contains a tissue thromboplastin. Besides there is in a saliva an incomplete thromboplastin representing the complex of negatively charged phospholipids (cell membranes breaks). In a saliva in a small concentration one can found almost all blood coagulation factors containing in a blood plasma, and also the fibrinolytic system components are found out there. The postponed stabilized fibrin (for example, in a removed tooth alveola) is a matrix for development of a connective tissue, that promotes the reparative processes and fast healing up of wounds in an oral cavity. Fast fibrinous clots formation interferes with an infection hit into the depth of an oral cavity wound.

In parotid and mixed saliva composition plasminogen and plasmin are absent, but there are plasminogen activator and proactivator. On its properties the plasminogen activator reminds of tissue activator. It is quite possible, that it gets in a saliva due to a diffusion from a blood. Besides the desquamated cells and leucocytes, being destructed, allocate trypsin-like and other proteases capable to lyse a fibrin. The fibrinolytic agents result in a vessels recanalization, that is accompanied by circulation restoration in an injured oral cavity. At the same time, the fibrinolytic agents presence in a saliva can render negative action as well. Quite often after odontectomy operation alveolar bleeding arise because of fast dissolution of a fibrinous clot. It is promoted by a stress experienced by many patients at the reference to dentist. The similar picture can arise also at operative measures in an oral cavity, at mandible fractures, gingival fissure liquidation and others. The fibrinolysis inhibitors local application in course of them promotes not only fast bleeding stoppage, but also leds to earlier operational wounds heat.

It’s necessary to remember, that at serious operative measures in oral cavity and soft face tissues disseminative intravascular coagulation (DIC) or DIC-syndrom can arise. Under these conditions the fibrinolysis inhibitors adsorption can considerably complicate its current.

 

 

Lecture 6

Respiration physiology. Oral cavity importance for speech respiration and speech-forming

 

Respiration is vitally essential for human beings and animals life. Respiration is gas exchange between organism external and internal environment. This process is performed in several stages:

1) External or lung respiration – performs gas exchange between organism external and internal environment (between air and blood).

2) Gas transition and transfer – is performed due to alveoles permeability and blood transport function.

3) Internal or tissular respiration – performs directly cellular oxidation process.

External respiration – is performed with cycles change, one respiratory act consists of inspiration and expiration phases. As a rule, inspiration is shorter than expiration. Inspiration act: thorax volume increases in 3 directions – vertical, sagittal and frontal. Why? There are some reasons:

· Diaphragm contraction (if diaphragm in rest state is shifted on 1 cm it leads to thorax increasing on 200-300 ml of air). Result of diaphragm contraction: decreasing (flattening) of its cupula; visceral organs (in abdominal cavity) pushing down, throrax increasing in vertical direction.

· Contraction of external oblique intercostal and intercartillaginous muscles: they are fixed to above-lied rib near spinal cord, to below-lied rib – near sternum. Result: throrax volume increasing in sagittal and frontal directions. Ribs are putted forward, up and towards. And it supports such lungs localization change.

· As lungs are connected with thorax through pleura visceral and parietal layers then lungs volume increasing occurs after thorax volume rising up. It leads to pressure decreasing in them. Pressure becomes lower than atmospheric one, air comes into lungs. Thus, negative pressure is third reason (factor).

· This negative pressure increases in course of inspiration because at lungs stretching their elastic draft - force with which lung strives for compression - is increased. Elastic draft is explained by 2 factors: there are many elastic fibres in alveoles walls - the first one – and the existance of surface tension of liquid tunic containing surfactants and covering alveole wall internal surface – the second one. Elastic draft (the 4-th factor of inspiration) is increased in course of inspiration, negative pressure is rised up in pleural cavity that encourages inspiration act.

Thus, inspiration is rather active process.

Expiration act – under usual conditions is performed passively by means of following factors:

· thorax gravity force;

· elastic graft of rib cartilages overwinded in course of inspiration;

· abdominal cavity organs pressure.

But expiration as inspiration may be also active (for instance, at hyperventillation, cough, someone’s straining and so on), when internal intercostal muscles contraction occurs. These muscles are fixed near spinal cord to below-lied rib and near sternum to above-lied rib and their contraction cause pushing ribs down, ahead and inside.

Respiratory muscles in course of their activity passe through some resistance, 2/3 of which is elastic, defined by lungs and thorax tissues as well as surfactant action; 1/3 – non-elastic caused by gas stream friction with air ways.

Negative pressure appearence in pleural fissure is explained by following fact: new-born thorax grows faster than lungs that’s why lung tissue is undergone to constant tension. Pleural layers possess large absorbtive ability that encourages negative pressure creation. That’s why gas introducing in pleural cavity is absorbed after some time and negative pressure is restored in pleural cavity. Thus, negative pressure is constantly supported in pleural cavity. If thorax is wounded than pressure in pleural fissure becomes equal to atmospheric one and lung is falling down, pneumothorax occurs. If we have liquid, blood and pus – the names will be correspondingly hydrothorax, haemathorax and pyothorax.

One can differentiate 2 main respiration types:

1) Thoracic (rib) – thorax dilation is connected mainly with ribs rising; respiration is mainly performed by means of intercostal muscles activity, diaphragm is moved passively according to interthoracic pressure change. This respiration type is a female.

2) Abdominal (phrenic or diaphragmal) – diaphragm contraction (flattening) is main respiration factor as the result of which interpleural pressure is decreased and simultaneousely interabdominal pressure is increased. This respiration type is more effective because lungs are ventillated in more extent and stronger in course of it and blood venous return is released from abdominal cavity organs to heart. Diaphragmal respiration is more physiologic! It is called male respiration. There exists one important rule for women: they must breath with thorax mainly only when their pregnancy!

Air amount in lungs after maximal inspiration is known as common lungs capacity (CLC). It is 4200-6000 ml in adults. Its compounds are: vital lung capacity (VLC) and residual volume (RV). VLC – air amount which leaves lungs in course of maximally deep expiration after maximally deep inspiration. It is equal to 3300-4800 ml under norma (in males 4000-4800 ml, in females – 3300-4000 ml). VLC consists of 3 lung volumes:

1) respirational volume (RV) of air inspirated and expirated in course of each respiratory cycle under rest state – 400-500 ml;

2) reserve inspiration volume – additional air that one can inspirate in course of maximal inspiration after usual inspiration – 1900-3300 ml;

3) reserve expiration volume – additional air that one can expirate in course of maximal expiration after usual expiration – 700-1000 ml.

At usual respiration we have reserve expiration volume and respirational volume in our lungs.

Residual volume – everything that is in lungs after deep inspiration - it is equal to 1200-2000 ml. It is in our lungs even after death!

There exists one more volume – harmful space volume – air part that is remained in air ways (nasal ducts, oral cavity, nasopharynx, nasal additional sinuses, trachea, bronchi) and doesn’t reach lungs (this air doesn’t participate in gas exchange). Such anatomical space is about 140-200 ml. It very useful despite its name “harmful” because air passing through them (especially when its passage through nasal ducts) becomes warm, humid, protected from side particles, bacterias. Respiration through nose is more physiological!

For 1 minute, at respiration freaquency equal to 16-20, one inspirates volume that has name of minute volume (MV). Its size depends on 2 compounds: respiration volume and respiration freaquency. Respiration freaquency 16-20 (norma indicated in all textbooks and manuels) per 1 minute is not ideally physiological. Less respiration freaquency which may be reach by corresponding training (the most often – physical training) - is more physiologic from the point of view delt with diseases prevention not only in respiratory appatarus but also in other organs and systems. Why less respiration freaquency is more physiologic? Describe these advantages on concrete example of trained person respiration. Imagine, please, 2 people before us, of equal constitution, but one of them is regularly done some kind of physical activity (regular morning exercise, running and so on). Respirational volume is always higher in trained person in comparison to untrained. Example. Respirational volume in trained person – 800 ml; in untrained - 400 ml. After small physical loading their respiration freaquency is getting increased: in trained person – to 20 respiratory acts per minutes, in untrained – rather higher (for example, 40). At such ziphras minute volume in both people will be equal to 16000 ml of air (400 ml x 40 and 800 ml x 20). In what are the advantages of one of them before other? In the first human being (trained) from 800 ml of respiratory volume 600 ml will come to alveoles with every inspiration (if both subjects have harmful space volume equal to 200 ml). In the second (untrained) person only 200 ml of air will come to alveoles. At respiration freaquency 20 in first person 12000 ml of air reach alveoles for 1 minute (20 x 600 ml). At a freaquency 40 in second person this air amount will be only 8000 ml of air (40 x 200 ml). Thus, in untrained person air amount reaching lungs is lower on 4000 ml. That’s why less respiration freaquency is more physiologic! It is reached by training (the best – by physical one). As it is known nowadays, civilized person is healthy, active, energetic and it may be so tens of years if his minute volume is not more than 4-5 l. The more minute volume predominates over this level, the more symptoms are of different organs pathologies occur. In people who have such problems (these are the civilization problems!!!) minute volume is equal to 8-12 litres in resting state. One can’t call such respiration healthy. Remember!!! External respiration normalization – reaching minute volume level 3-4 litres per minute! High freaquency of our breathing is delt with its uncorrect character. In the most people amount time for inspiration is approximately equal to time for expiration. Besides, the most people performes their expiration right after their inspiration – it is also out of physiology. It’s necessary to lack someone’s breathing after inspiration and then slower then inspiration expiration comes, after which – new lack. Such respiration type reminds respiration on Buteyko, Frolov et al. But, unfortunately, people become follow this respiration “culture” only when they fell ill. Really it’s necessary to breath in such a way always! This is a Real Way to health and prevention of a great number of diseases!

Lung ventillation. Air-conductive ways, lung parenhyme, pleura, osteo-muscular thorax carcas an diaphragm are united working organ by which lung ventillation is performed. Lung ventillation – alveolar air gas content renewal process. Such air provides oxygen coming into alveoles and carbon dioxide excessive amount releasing. Ventillation intensivity is determined by respiration depth and freaquency, harmful space. Ventillation occurs due to active physiologic process (respiratory movements). It depends on body stature (vertical or horizontal) and circulation in alveoles.

Gas transition and transfer mechanism. Pressure gradient is vitally essential factor providing gas exchange from one environment to another. What pressure does it mean? Oxygen and carbonic dioxide create definite pressure which is called partial pressure – common pressure part of a given gas in a given mixture. This part depends on gas per cent content in the mixture. The it is more, the partial pressure of given gas is more.

Oxygen transport.

Oxygen partial pressure:

· in atmosphere is equal to 159 mm merc col.;

· in alveoles – 102-105 mm merc col;

· in venous blood reaching alveoles – 40 mm merc col;

· pressure gradient for oxygen between alveoles and blood is about 60 mm merc col.

Thus, oxygen due to this difference of partial pressure and its tension in different environments passes from atmosphere into alveoles and then in blood and tissues. How oxygen is transmitted?

Oxygen transfer conditions

It is known that blood tranfers 300-350 ml of oxygen for 1 minute under relative rest state (this ziphra significantly increases at physical work). One can differentiate 2 factors of oxygen transfer:

· large alveolar surface (60-100 square meters);

· oxygen fast diffusion ability – at this difference between alveoles and blood in 1 mm merc col 200 ml of oxygen will diffund; at a real difference that is 60 mm merc col – 12000 ml of oxygen (!even in course of intensive physical loading this ziphra is not more than 4000-5000 ml!). You see data about oxygen diffuse ability: it predominates the level necessary for intensive physical trainings in 2,5-3,0 times.

Oxygen transport forms

Particularly oxygen can be dissolved (in 100 ml of blood – up to 0,3 ml of oxygen, thus, in all blood – about 15 ml). Of course, it can’t solve the problem of oxygen transport. Main chemical substance necessary for oxygen transport is oxyhaemoglobine. It was estimated that 1 g of haemoglobine can transmits approximately 1,31 ml of oxygen. 100 ml of blood contains about 14-16 g of haemoglobine, so, they can carry 18-21 ml of oxygen. This index is known as oxygen blood capacity – is is defined as oxygen amount transporting with 100 ml of blood till its full saturation. This index can be changed. It is rised up in course of physical training, at polycitaemia; reduced – at blood diseases for instance at anaemias.

Formed oxyhaemoglobine amount depends on oxygen partial pressure in blood. This dependence is linear that is proved by following data. At oxygen partial pressure equal to 0, oxyhaemoglobine isnt’t formed; 10 mm merc col. – 10% oxyhaemoglobine; 20 mm.- 30%; 40 mm. – 70%; 70 mm.- 90%; 100 mm. – 96%. If we connect all this points we shall receive curve describing dependence between oxygen tension in blood and amount of forming oxyhaemoglobine. This curve name is oxyhaemoglobine dissociation curve. One can make some important conclusions from this curve:

1) At oxygen partial tension decreasing in blood up to 80-70 mm merc col (it corresponds to such partial pressure in mountains at a high 2500-3000 meters above sea level) amount of formed oxyhaemoglobine decreases insignificantly, i.e. its amount is less only on several per cents than on plain. It gives the possibilities to successful work of mountaineers, highland workers and also to life in highlands without any additional devices and forces. At a high level above 4000 metres we’ll not be able to breath without additional oxygen coming from gas cylinder.

2) Venous blood is rich in oxyhaemoglobine, i.e. it is saturated by oxygen. At partial tension in venous blood equal to 40 mm merc col, up to 70% of oxyhaemoglobine is formed in blood.

3) Difference between oxyhaemoglobine content in arterial and venous blood is 25-26%. Oxyhaemoglobine content in arterial blood is 95-96%, in venous – 70%. This index is named arterio-venous difference. It is rised up in course of physical training, at polycitaemia; reduced – at blood (at anaemias) and heart disorders.

Oxyhaemoglobine dissociation curve moving:

1) to the left (up) – is observed:

· at temperature decreasing;

· pH increasing (alkalosis);

· hypocapnia;

· in blood reaching lungs;

· in new-borns;

· in mountaineers;

· in fliers;

· in cosmonauts.

Essence: at less oxygen partial pressure in atmosphere to form more oxyhaemoglobine in blood.

2) To the right (down) – is observed:

· at hyperthermia;

· at fever;

· pH decreasing (acidosis);

· carbonic acid content increasing;

· in blood reaching tissues (for example, working muscles).

Essence: at the same oxygen partial tension oxygen forming is less and free oxygen comes to the tissue where it’s necessary for redox reactions performing in them.

Carbon dioxide transport

Carbon dioxide transmission and transfer is realized by same machanisms. Carbon dioxide tension:

· in tissues – maximal – 60 mm merc col.;

· in venous blood outflowing from tissues – 46 mm;

· in alveoles where venous blood inflows – 38 mm merc col;

· in atmosphere – 0,2 mm merc col.

It’s quite naturally that pressure and tension gradient in different organism environments and compartments provides carbonic dioxide transition from tissues to blood, from blood into alveoles and from alveoles into surrounding space.

Carbon dioxide forms

Particularly, like oxygen, in little amounts it can dissolve (3-6%). Rest part comes into chemical connections both in plasma and in erythrocytes. Chemical substance of carbonic dioxide with water – carbonic acid (H2CO3) – appears in plasma. It takes place because partial tension of this gas is more than in blood, that’s why it transfers into blood plasma where is connected to water. Carbonic acid part in plasma is connected to sodium chloride as the result of which soda is formed (NaHCO3). Plasma transports carbonic dioxide in composition of theses compounds. Its rest part reaches erythrocytes where under influence of special erythrocytic enzyme carboanhydrase the possibility of its connection with water is significantly increased with carbonic acid forming. Little amount of this acid is binded with potassium chloride with potassium bicarbonic (KHCO3) formation. Finally, carbon dioxide part is binded to amine group of haemoglobine with the carbohaemoglobine (KHCO2)forming. Thus, in erythrocytes carbonic dioxide is transported in a structure of H2CO3, KHCO3 and HbCO2.

When blood reaches alveoles, same enzyme carboanhydrase acts on the contrary: it helps H2CO3 dissociation and CO2 comes into alveoles as the result of these processes. As oxygen partial pressure in alveoles is higher than in blood the gas passes in blood, in red blood cells with oxyhaemoglobine forming in them. Being more powerful acid than carbonic, oxyhaemoglobine takes the bases from bicarbonates and thus provides carbonic dioxide releasing. The result: CO2 passes into alveoles. In tissues oxyhaemoglobine transformes into haemoglobine giving bases connected with it, increasing blood saturation with CO2. These examples testify to the fact that oxygen plays essential role in CO2 forming and releasing.

But at all these reactions CO2 tension in venous blood remains big (46 mm merc col) and it doesn’t differ significantly from its tension in arterial blood. Thus, there exists carbonic dioxide arterio-venous difference equal to 6 mm merc col.

There is quite natural question: why organism has big amount of CO2? The answer is the following: it is essential respiration regulator.

Respiration regulation is performed by means of reflectory reactions occuring as a result of excitement of specific receptors located in lung tissue, vascular reflexogenic zones and other regions. Respiration regulation central apparatus are the structures of:

· spine;

· medulla oblongata;

· hypothalamus;

· brain hemispheres.

Main function of respiration management is performed by stem repiratory neurons which transmit rhythmic sygnals into spine to respiratory muscles motoneurons.

Respiratory nervous center – is central nervous system neurons integrity providing respiratory muscles co-ordinated rhythmical activity and external respiration constant adaptation to changing conditions inside organism and in environment. Main (working) part of respiratory nervous center is located in medulla oblongata. One can differentiate 2 parts in it: inspiratory (inspiration center) and expiratory (expiration center). Medulla oblongata respiratory neurons dorsal group primarily consists of inspiratory neurons. They give particularly the stream of descendant ways getting the contact with diaphragmal nerve motoneurons. Respiratory neurons ventral group sends primarily descendant fibres to intercostal muscles motoneurons. One can see region in pons anterior part called as pneumotaxic center. This center deals with activity both of inspiratory and expiratory center parts providing the change of inspiration and expiration. Respiratory center important part is neurons group of spine cervical part (III-IV cervical segments), where diaphragmal nerves nuclei are situated.

Respiratory center excitement mechanisms are the following.

· One of the most important ways of its excitement is automatism. There is not one point of view to automatism nature but there exist data about secondary depolarization occurence in respiratory neurons (like diastolic depolarization in myocardium) which reaching its critical level gives new impuls.

· But one of main ways of respiratory center excitement is its irritation by carbonic acid. As it was mentioned above, there remains much carbonic acid in blood leaving lungs. It performs the function of medulla oblongata neurons main irritator. It is mediated through special structures – chemoreceptors, located directly in medulla oblongata structures (“ central chemoreceptors ”). Thus, the second way – through blood.

· They are very sensitive to carbonic dioxide tension and acid-alkaline state of intercellular liquor washing them.

· Carbonic acid can easily diffund from brain vessels in liquor and stimulates medulla oblongata chemoreceptors.

· Reflectory way - there are 2 reflexes groups (like for cardio-vascular system): proper and conjugated.

I. Proper reflexes – the reflexes originated from respiratory system organs and finished in it.

1) Reflex from lung mechanoreceptors. According to localization and type of percepted irritations, reflectory answer to irritation one can differentiate 3 types of such receptors: receptors of stretching, irritant receptors and lung juxtacapillar receptors.

· Lung stretching receptors are primarily located in air ways (trachea, bronchi) smooth muscles. There are approximately 1000 receptors in every lung and they are connected with respiratory center by large myelinized afferent fibres of vagus with very high conductance velocity. Direct irritator – internal tension in air ways walls tissues. Such impulses freaquency is increased at lung stretching in course of inspiration. Lung swelling causes inspiration reflectory inhibition and transition to expiration. These reactions are stopped at vagus cutting and respiration becomes retarded and deep. Mentioned reactions are called Gering-Breyer’s reflex. This reflex is reproduced in adult person when his respiratory volume is more than 1 l (at physical training for instance). It is of essential importance in new-borns. Their adaptation is slow.

· Irritant receptors or slowly adaptating air ways mechanoreceptors, trachea and bronchi mucosa receptors. They answer to lung volume significant changes, chemical or mechanical irritators (mucus, tobacco, dust particles and so on) action to mucosa. Their adaptation is fast. At side bodies coming into respiratory ways there occurs cough reflex after irritant receptors activation. Reflectory arch of cough reflex – receptors – superior-laryngeal, glosso-pharyngeal, trygeminal nerves – expiratory part of respiratory center. Result - strong expiration – cough. At isolated irritation of nasal respiratory ways receptors second immediate expiration occurs – sneezing.

· Juxtacapillary receptors are located near alveolar and respiratory bronchi capillaries. Irritators: pressure increasing in circulation small circle and intersticial liquid volume increasing in lungs. Such situation is observed at blood stagnation in small circulation circle, lung oedema, lung tissue injury (at pneumonia et al.). Impulses from these receptors are directed to respiratory center through vagus causing freaquent surface breathing occurence. There may be not only freaquent breathing (tachypnoe) but also reflectory bronchoconstriction.

2) Reflexes from respiratory musculature proprioreceptors:

· Reflex from intercostal muscles proprioreceptors is realized in course of inspiration when these muscles while their contraction send information through intercostal nerves to respiratory center expiratory part and as a result expiration occurs.

· Reflex from diaphragm proprioreceptors – is performed as an answer to its contraction in course of inspiration. Result: information comes through diaphragmal nerves first in spine, than in medulla oblongata in its expiratory part and expiration occurs.

Thus, all respiratory system proper (own) reflexes are realized in course of inspiration and are resulted in expiration.

II. Conjugated reflexes – reflexes originated out of respiratory system.

1) Reflex onto conjugation of blood circulation and respiration systems – is originated from perypheral chemoreceptors of vascular reflexogenic zones. The most sensitive of them are located in sino-carotid zone region.

· Sino-carotid chemoreceptive conjugated reflex – is performed at carbonic dioxide accumulation in blood. If its tension increases than the irritation of the most sensitive chemoreceptors (they are in this zone in sino-carotid body) occurs, excitement wave comes from them through IX pair of cranio-cerebral nerves and reaches respiratory center expiratory part. Expiration occurs which enforces releasing of excessive carbonic acid in surrounding space. Thus, blood circulation system (while this reflectory act performance it works more intensively: heart contractioin freaquency and blood stream velocity increase) influences on respiration system.

2) Exteroceptive reflexes are originated from tactile (remember your breathing reaction on touching of lovely person), temperature (warmth – increases, coldness – decreases respiratory function), noceoceptive (weak stimuli and of a middle force - increase, strong – suppress breathing) receptors.

2) Proprioreceptive reflexes – are performed due to irritation of receptors of sceletal muscles, joints, ligaments. It is observed in course of physical training doing. Why? If under rest state it’s necessary 200-300 ml oxygen per minute for human than at physical loading given volume must be significantly increased. Under these conditions both minute volume and arterio-venous difference on oxygen are increased. This indexes increasing is accompanied by oxygen consumption rising up. At work duration of only 2-3 minutes and its significant power oxygen consumption grows uninterruptedly from the very beginning of work and is decreased only after its stoppage. At work duration more, oxygen consumption, while increasing in course of first minutes, is supported all the time on its constant level. Oxygen consumption increases the more the harder physical work it is. Maximal oxygen amount that organism can use per 1 minute at the hardest work for it is called oxygen maximal consumption (OMC). Work at which person reaches his OMC level must have duration not less then 3 minutes. There exist many ways of OMC determining. It doesn’t predominate 2,0-2,5 l/min in untrained people. It can be twice large in sportsmen and even more. OMC is an index of organism aerobic productivity. This human ability to perform very hard physical work, providing his energetic consumption due to oxygen used directly in course of work. It is known that even well-trained person can work at oxygen consumption 90-95% from his OMC level not more than 10-15 min. One having more aerobic productivity reaches better results in work (sport) at practically equal technic adn tactic preparation. Why oxygen consumption is increased in course of physical activity? One can differentiate several reasons:

· additional capillaries opening and blood increasing in them;

· oxyhaemoglobine dissociation curve movement to the right and below;

· temperature increasing in muscles.

For performing their work, muscles need in energy, the accumulations of which are restored while oxygen transport. Thus, there exists definite dependence between work power and oxygen amount necessary for work. That blood amount necessary for work is called oxygen asking. Oxygen asking can reach up to 15-20 liters per minute and even more in course of hard work. But maximum of oxygen consumption is less in 2-3 times. Does it possible to perform the work if minute oxygen accumulation predominates OMC? For correct answer this question one should remember for what oxygen is used in course of muscular activity. It is essential for macroergic substances restoration providing muscular contraction. Usually oxygen interacts with glucose and it releases the energy while its oxidation. But also glucose can be destructed without oxygen, i.e. by abaerobic way as a result of which energy releases too. These are also other substances possessing the ability to be destructed without oxygen. Thus, muscular activity can be provided at insufficient oxygen coming into organism too. But in this case many acid products are formed and it’s necessary oxygen for their destruction because they are destructed by oxidation. Oxygen amount necessary for metabolism products oxidation that were formed in course of physical activity is called oxygen debt. It appearsin course of work and is liquidated in restoration period after work end. Usually this disappearing takes from several minutes to 1 hour and a half. Everything depends on work duration and intensivity. Lactic acid plays the most important role in oxygen debt forming. To continue his work at lactate presence in blood in great amounts organism must have powerful buffer systems and his tissues are to be adapted to work under hypoxy conditions. Such organism adaptation serves as one of factors providing high aerobic productivity. All the mentioned above complicate respiration regulation at physical activity because oxygen taking in organism is increased and its blood hypoxy leads to chemoreceptors irritation. Sygnals from them come in respiratory center as the result of which respiration becomes more freaquent. A great number of carbonic acid is formed in course of muscular activity that comes into blood and it can acts to respiratory center directly through central chemoreceptors. If blood hypoxy leads primarily to breathing quickening than carbonic acid surplus causes its deepening. Both theses factors act simultaneousely in course of physical activity and that’s why respiration quickening and deepening takes place. Finally, impulses coming from working muscles, reach respiratory center and enforces its activity. At respiratory center functionning all its parts are functionally interconnected by means of following mechanism: at carbonic acid accumulation respiratory center inspiratory part is excited from information comes in pneumotaxic part, then to its expiratory part. The latest, besides, is excited by means of a whole group of reflectory acts – from receptors of lungs, diaphragm, intercostal muscles, respiratory ways, vessels chemoreceptors. Inspiration center activity is inhibited due to its excitement through special inhibitory reticular neuron and inspiration is changed by expiration. As expiration center is inhibited it doesn’t send impulses far into pneumotaxic center and information flow is stopped from it to expiration center. Carbonic acid is accumulated in blood by this time and inhibitory influencings on expiratory part are inhibited. Inspiration center is excited due to such information flow redisposition and expiration is changed by inspiration. And everything is repeated again.

Vagus is an essential link in respiration regulation. Main influencings to expiration center come through it. That’s why at its injury (like at pneumotaxic center injury) respiration is changed so that inspiration remains normal and expiration is sharply prolonged – vagus-dyspnoe.

As it was mentioned above in course of coming to the highlands lung ventillation increasing occurs based on vascular zones chemoreceptors stimulation.

Heart contraction freaquency and minute volume are increased simultaneously with this. These reactions improve oxygen transport in organism a little but not for long. That’s why at durable staying into mountains with adaptation to chronic hypoxy initial (urgent) respiration reactions gradually leave their place to more economic adaptation of gas-transport organism system. In constant residents of highlands respiration reaction to hypoxy is too weak (hypoxic deafness) and lung ventillation is supported practically on the same level like in plane residents. At the same time at durable staying under conditions of highlands vital lung capacity, caloric oxygen equivalent, myoglobine content in muscles, mitochondrial enzymes activity (providing biological oxidation and glycolysis) are increased; organism tissues (particularly central nervous system) sensitivity to insufficient oxygen supply is decreased. At high more than 12000 m air pressure is very small and under these conditions even breathing by pure oxygen doesn’t solve the problem. That’s why at flyings at this high one need hermetic cockpits (planes, cosmic ship).

Sometimes human being has to work under increasing pressure conditions (divering). In the depth nitrogen becomes its dissolving in blood and in course of fast rising out off the depth it doesn’t manage to release from blood, gas vesicles cause vessel emboly. Occuring condition is called kessonic disease. It is accompanied by pain in joints, giddiness, dyspnoe, unconsciousness. That’s why nitrogen in air mixtures is changed on insoluble gases (for instance, helium).



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