Dentistry First Term 2022 PDF

Blood  Blood Blood is a vital fluid circulate within Cardio Vascular System (CVS), and its volume is 5600ml. Blood Functions: 1- Transport function (glucose, O2, CO2). 2- Defensive function (WBCs, anti-bodies). 3- Hemostatic function (stop bleeding). 4- Homeost...

Blood  Blood Blood is a vital fluid circulate within Cardio Vascular System (CVS), and its volume is 5600ml. Blood Functions: 1- Transport function (glucose, O2, CO2). 2- Defensive function (WBCs, anti-bodies). 3- Hemostatic function (stop bleeding). 4- Homeostatic function (keeps the composition of the tissue fluid constant). Blood Composition: 45% cells: 1- Red blood corpuscles (RBCs). 2- White blood cells (WBCs). 3- Platelets 55% plasma: 1- Water 90 %. 2- Inorganic substances (Na, Cl). 3- Organic substances (protein, lipid, glucose). 4- Gases (CO2, O2). PLASMA PROTEINS Concentration: 7.2 gm /dl. Composition: 1- Albumin : its concentration 3.5 – 5 g/dl. 2- Globulin : its concentration 2.5 g/dl. 3- Fibrinogen : its concentration 0.4 g/dl. 4- Prothrombin: its concentration 0.01 g/dl. Site of formation: All types of plasma protein are formed in liver except 50% of Globulin formed in plasma cells. 1 Functions: A- Specific functions: 1- Osmotic function it is function of albumin where water withdrawn from tissue to plasma by osmotic pressure of albumin (28 mmHg). 2- Defensive function it is function of gamma globulin while alpha and beta globulin have transport function. 3- Viscosity of the blood it is function of fibrinogen, the importance of this viscosity is to maintain arterial blood pressure. 4- Clotting of the blood it is function of fibrinogen and Prothrombin. B- Nonspecific functions: 1- Plasma proteins act as a carrier for important elements of the blood (vitamins, hormones). 2- Buffer function: plasma proteins adjust PH of blood at 7.4. Buffering function of plasma protein represent 15% of buffering power of blood. 3- Diet reserve: plasma proteins act as a source for rapid replacement of tissue protein. 4- Capillary permeability: plasma proteins control movement of substances across capillaries (in and out) through the pores. 2  RED BLOOD CORPUSCLES (RBCs) RBCs are the highest concentration of cells in the body. - In male = 5.5 million/mm3. - In female = 4.8 million/mm3. - RBCs are non nucleated, biconcave shape to provide large surface area for transport and to enhance cell flexibility. - RBCs life span = 120 day. 3  Erythropoiesis It is process of formation of RBCs. Erythropoiesis takes place in: Fetus → liver and spleen. Children → bone marrow of all bones. Adult → bone marrow of long bones. Above 20 year → bone marrow of membranous bones. Factors affecting erythropoiesis: 1-Healthy bone marrow 2- Liver and Kidney 3- Oxygen supply to tissue 4- Hormones 5- Diet 1- Healthy bone marrow is essential for formation of normal RBCs as it is site of formation. Destruction of bone marrow leads to anemia known as aplastic anemia which is (normocytic normochromic anemia). Bone marrow may be destroyed by drugs, radiation, and tumors. 2- Liver and kidney are essential for formation of normal RBCs as both are site of formation of erythropoietin hormone (15% liver – 85% kidney ) also liver is considered to be site of storage of iron and B12. 3- O2 supply to tissue is one of the most important factors in formation of RBCs decrease O2 supply will lead to stimulation of formation of RBCs through increase Erythropoietin hormone. Decrease O2 supply occurs in heart and lung disease, high altitude, and haemorrhage. 4- Hormones erythropoietin – androgen – cortisone and thyroid hormone are essential for formation of RBCs. 4 5-Diet Diet must contain vitamins as folic acid and B12, metals as iron, copper and cobalt and protein for formation of RBCs. Erythropoietin hormone site of formation: Fetus > liver Adult > 15% liver and 85% kidney Erythropoietin stimulated by : 1- Hypoxia 2-Alkalosis 3- Androgen 4- Adenosine 5- Cobalt salt 6- Catecholamine Erythropoietin hormone accelerates all stages of erythropoiesis and that is why in renal failure patient develops anemia. 5 Iron absorption 1- Iron absorbed in ferrous state while iron in diet is ferric. 2- Reduction of ferric to ferrous occurs by gastric Hcl and ascorbic acid (vitamin C). 3- Iron absorbed mainly in upper part of small intestine (duodenum). 4- Part of iron is delivered to mitochondria. 5- Remaining part is either combined with apoferritin (in intestine) or carried in plasma on transferrin. 6- Iron combined with apoferritin is changed to ferritin which is main storage of iron. 7- Iron transported in blood bound mainly to transferrin to all part of body and stored in liver as ferritin. 8- Deficiency in iron is due to decrease iron intake or decrease iron absorption or chronic blood loss lead to microcytic anemia. NB: apoferritin is present in intestine and liver. 6 B12 absorption 1- Intrinsic factor secreted by gastric gland (parietal cell). 2- Intrinsic factor combines with vitamin B12 for protection and transport of B12. 3- Vitamin B12 absorbed from lower part of small intestine (ileum). 4- Vitamin B12 enter mucosal cell with Intrinsic factor by pinocytosis. 5- Inside cell vitamin B12 set free in order to be absorbed to blood where it bound to transcobalamineII to every part in the body and stored in liver. 6- Deficiency in vitamin B12 may be due to decrease in vitamin B12 absorption lead to anemia known as macrocytic anemia. Iron B12 Function important for formation of - DNA formation hemoglobin and myoglobin - Cell division - Cell maturation - Formation of myelin sheath Storage in liver in liver Requirement 0.6 mg/day 5 g/day Site absorption upper part of small intestine lower part of small intestine Need Hcl and vitamin C for reduction intrinsic factor for protection of ferric iron to ferrous from Hcl Deficiency lead to microcytic anemia macrocytic anemia 7  Anemia Anemia is a decrease in number of RBCs, hemoglobin content or both. Anemia is considered when RBCs count → < 4.5 million in males & < 3.9 million in females & Hb content → < 13.5 gm % in males < 11.5 gm % in females. Blood indices: 1-Mean corpuscular Hb (MCH) = amount of Hb in single RBC = Hb content X 10 RBC count in million - Normally, it is 25-32 picogram. - Values less than 25 picogram are called hypochromic. 2-Mean corpuscular volume (MCV) = volume of single RBC = Hematocrit value X 10 RBC count in million - Normally, it is 80 -95 µ3 - Values less than 80 are called microcytes and values more than 95 are called macrocytes. Anemia is classified according to blood indices into: 1-Normocytic normochromic anemia : i.e normal blood indices 2-Microcytic hypochromic anemia : i.e lower blood indices 3-Macrocytic anemia : i.e. higher blood indices. 1-Normocytic normochromic anemia: Causes: a- Aplastic anemia: decrease RBC synthesis due to bone marrow inhibition by: antibiotic – malignant tumor – irradiation. 8  b- Hemolytic anemia: excessive hemolysis of RBC c- Acute blood loss: (Acute haemorrhage). 2- Microcytic hypochromic anemia: Small RBC with low Hb content inside caused by iron deficiency Causes of iron deficiency anemia: a- Decrease dietary intake: → starvation as in children & pregnancy where there is increase in their needs. b- Decrease iron absorption as in: - Gastrectomy where HCl is absent - Small intestine diseases - Vitamin C deficiency - increase phosphate & phytate where they form insoluble salts with iron. c- Chronic blood loss: as in piles, peptic ulcer & ankylostoma. N.B. Tea decrease iron absorption because it contains tannic acid & theophylline 3- Macrocytic anemia: Due to decrease vit B12 or folic acid → decrease DNA → decrease proliferation of erythroblasts → megalocytes which are macorcytes. Causes folic acid deficiency: vit B12 deficiency: Pernicious anemia: - It is a familial disease of elderly & more common in women - It is an autoimmune disease- There is an immune reaction against gastric parietal cells leading to achlorhydia and absent intrinsic factor. - There is degeneration of posterior and lateral column of spinal cord leading to neurological manifestations. 9  Treatment of anemia: 1- In each type, try to treat the cause: a- In iron deficiency : give ferrous salts by mouth, in severe cases give iron by injection. b- In pernicious anemia: give B12 by injection through the whole life. c- Macrocytic anemia due to folic acid deficiency is treated by folic acid. 2- In severe cases, blood transfusion is needed 10  Blood groups ABO system: - The cell membrane of RBCs contains mucopolysaccharide substances called antigens. Two types of antigens are known: A antigen & B antigen. - People are classified into 4 groups according to antigen (agglutinogen) on RBC membrane; the plasma contains antibodies (agglutinins) against the absent antigen. Group A B AB O % of people 40 10 5 45 Antigen A B A&B - Antibody Anti-B Anti-A - Anti-A & Anti-B - Blood group A : A antigen is present - Blood group B : B antigen is present - Blood group AB : A & B antigens are present - Blood group O : Neither A nor B antigens are present. - If an antigen is present in RBCs and the plasma contains its corresponding antibodies → agglutination → hemolysis. - The antigens are called agglutinogen and the antibodies are called agglutinins. Importance: 1-Medicolegal importance (Disputed Parenthood): Inheritance of blood groups is by 2 antigens from both father & mother The A & B antigens are dominant, while the O one is recessive. Blood group is a good negative test in disputed parenthood. 2-Blood transfusion: In incompatible blood transfusion, the donor RBCs is agglutinated by recipient plasma, as the donor’s plasma is diluted by the recipient blood. *Group O is universal donor, because there is no agglutinogen. 11 *Group AB is universal recipient, because there is no agglutinin *Cross matching test: should be done before blood transfusion in which the recipient plasma is mixed with donor’s RBCs, and recipient RBCs is mixed with donor plasma, If no agglutination→transfusion is done. Rh factor (D factor): -It is a system composed of C, D, E antigens -It is first discovered in blood of Rhesus monkey -D is the most antigenic component. -85 % of people are Rh positive i.e. have D antigen. -15 % of people are Rh negative i.e. have no D antigen. -Normally Rh + Ve & Rh – Ve have no anti-D -Negative Rh persons forms anti D if antigen D is transformed to them. -Positive Rh never form anti D, whether receives Rh +Ve or Rh -Ve Importance: 1) Erythroblastosis Foetalis: (Rhesus hemolytic disease of the newly born) The disease occurs if: - An Rh negative female is married from an Rh positive male & she carries an Rh positive fetus - At delivery of this first baby (which will be born normal), little fetal blood leaks into maternal circulation. - Mother will produce anti-D agglutinins (IgG) - During next pregnancy, maternal agglutinins (IgG) cross the placenta causing fetal hemolysis leading to : Anemia of fetus Jaundice, increase bile pigments which cross the undeveloped blood brain barrier and deposit in basal ganglia (Kernicterus). 12  The first baby is affected in case of maternal sensitization by: - Previous Rh + Ve blood transfusion - Fetal maternal hemorrhage during pregnancy. The disease can be prevented by: - Avoiding Rh + Ve blood transfusion to Rh – Ve females. - Anti-D antibodies are given to neutralize the Rh +Ve fetal cells and prevent maternal sensitization. *If baby is born alive, he would be treated by exchange transfusion with blood group O Rh negative. N.B. No fetal complication regarding ABO system because ABO antibodies cannot cross the placenta (IgM). 2) Repeated blood transfusion: - If Rh – Ve persons is transfused with Rh +Ve blood, he will produce agglutinins against Rh factor. - If this person is transfused (later on) with Rh +Ve blood, agglutination occurs. Blood transfusion Indications: 1) To restore whole blood as in haemorrhage. 2) To restore one element: RBCs, WBCs & platelets. 3) Erythroblastosis foetalis. Precautions: 1) Compatible. 2) free from contamination. 3) High Hb content. 4) Free from disease. 5) Fresh i.e. less than 2 weeks storage. Complications: 1) Mechanical: air or fat embolism 2) Physiological: excess transfusion → overloading →heart failure. - Pyrogenic reaction → fever. 13 3) Infective: infective hepatitis, malaria, AIDS. 4) Incompatibility: Transfusion with incompatible blood leads to clumping & hemolysis of given RBCs leading to: a- Blockage of blood capillaries: This occurs by clumping RBCs leading to →backache and joint pain. Blocking of coronary vessels leads to → angina pain b-Intravascular hemolysis leads to : 1. Shock due to release of histamine and vasodilators-→drop of arterial blood pressure. 2. Liberation of K+ (hyperkalemia)→cardiac arrhythmia. 3. Liberation of Hemoglobin which: a. is broken to bilirubin leading to yellow coloration of skin and mucous membrane (jaundice) b. Leads to blockage of renal tubules as it is filtered by renal glomeruli →leading to renal failure. 14  Hemostasis It is prevention of blood loss after injury and is done by the following mechanisms: 1- Vascular spasm i.e. vasoconstriction. 2- Platelet reactions and temporary hemostatic plug formation. 3- Formation of blood clot. 1-Vascular spasm: it results from: a- Nervous reflexes which are initiated by pain from ruptured vessels. b- Myogenic spasm of vessel due to trauma. c- Local factors: as serotonin, thromboxane A2 (released from platelets). 2-Platelets - Platelet’s count = 150,000 – 300,000 / mm3 - Platelets are non-nucleated oval in shape. - Platelets formed in bone marrow. Role of platelets in hemostasis (Functions of platelets): 1- Platelet adhesion platelet adhere to subendotheial collagen in presence of: I- glycoprotein layer of platelet II- von- willbrand factor 2-Platelet activation platelet swell, change in shape and put out pseudopodia. Platelet activation is stimulated by: I – ADP II- thrombin 3-Platelet release Platelet release its contents Platelet release 3 important substances: I – Serotonin which produce vasoconstriction II – ADP which stimulate aggregation 15  III- Thromboxane A2 which produce vasoconstriction and aggregation 4-Platelet aggregation Platelets stick to each other Platelet aggregation stimulated by: I - Thromboxane A2 II- ADP 5-Platelet procoagulant (Help coagulation through PF3) From the membrane of platelet PF3 exposed which form ideal surface for concentration of clotting factor. 6-platelet Fusion platelet fuses to each other in presence of ADP 16  Clotting mechanisms - Clotting factors are present in plasma in an inactive form. - Clotting mechanisms concern with activation of an inactive clotting factor lead finally to formation of fibrin clot. Fibrin formation occur through 2 pathways: 1- Extrinsic pathway Extrinsic pathway start by release of thromboplastin from injured tissue. Thromboplastin activates factor VII. Factor VII active activate factor X. Factor X active convert prothrombin to thrombin in presence of Ca, platelets and factor V. Thrombin converts fibrinogen to fibrin monomer. Fibrin monomer converted to fibrin clot by active factor XIII and Ca. 2- Intrinsic pathway Collagen fiber activate factor XII this activation is helped by high molecular weight kininogen and plasma kallikrein. Active factor XII activate factor XI. Active factor XI activate factor IX. Active IX, active VIII, Ca and platelets form complex activate factor X. Factor X active convert prothrombin to thrombin in presence of Ca, platelet and factor V. Thrombin converts fibrinogen to fibrin monomer. Fibrin monomer converted to fibrin clot by active factor XIII and Ca. 17 Important notes: 1- When blood vessel ruptures, blood clotting is initiated by both systems simultaneously. 2- The extrinsic system is very rapid (15 sec) & very extensive, while the intrinsic is slower (1-6 min). 3- Ca++ is required for promotion of all steps except the first 2 steps of the intrinsic way. Ca++ level rarely falls to level that affect clotting. 4- There is a link between intrinsic & extrinsic pathway: activated factor VII(extrinsic) & factor IX (intrinsic) activates factor X (common pathway). 5- Vitamin K is important for activation of factors II, VII, IX and X. 18  Anti-coagulants Anti-coagulants are substance that prevent blood clotting In vitro In vivo 1 Oxalate salt Heparin 2 Citrate salt Dicumarol 3 Silicon 4 Heparin Dicumarol Heparin 1- Source Plant source Basophils, mast cells & liver 2-Intake Oral (by mouth) Injection intravenous i.v. & intramuscular i.m. 3- Onset & Slow onset & long duration Rapid onset & short duration duration 4- Chemistry Similar to vitamin K Sulphated mucopolysaccharide 5- Site of action Only in vivo In vivo & In vitro 6- Action Competes with vitamin K. So, -It increases antithrombin III inhibits its utilization by liver activity. (competitive inhibition). - It prevents activation of factor IX It decreases synthesis of - It has a clearing action→it factors II, VII, IX, X, prtn C & increases lipase enzyme which clears prtn S. blood from lipids after meals. 7- Antidote Vitamin K Protamine Sulphate 1% (basic protein) 19  Abnormalities of Hemostasis (1)Vitamin K deficiency: -Vitamin K is important for synthesis of factors II, VII, IX & X by liver -It is synthesized by bacterial flora of intestine (it is advisable to delay circumcision one month after birth). -Its deficiency leads to deficiency of factors II, VII, IX & X. -Causes of its deficiency: a- Sterility of intestine as in: 1- Newly born infants. 2- Long treatment with antibiotics b- Decrease absorption as in: 1- Obstructive jaundice 2- Fat malabsorption because vit K is fat soluble vitamin a- Liver diseases. d- Anticoagulants: which act by competitive inhibition with vit. K (2)Hemophilia: Hereditary, congenital, sex linked recessive disease carried by female, transmitted always to male (carried on X chromosome). - It is 3 types: Hemophilia A due to deficiency of factor VIII (85 % of cases) Hemophilia B due to deficiency of factor IX (10 % of cases) Hemophilia C due to deficiency of factor XI ( 5 % of cases). - It is characterized by severe prolonged bleeding on mild trauma. - Clotting time is prolonged. 20  LEUKOCYTES, WHITE BLOOD CELLS (WBCs) AND IMMUNITY Total Leukocytic Count: Total leukocytic count is ranges 4000 - 10,000/mm3 of blood. Types (Differential Leukocytic Count): According to the presence or absence of cytoplasmic granules, leukocytes are classified into granular and agranular. Types of WBCs I. Granular leukocytes (Granulocytes): classified into: 1. Neutrophils ( microphage): They constitute 50 - 70% of leukocytic count. The main function of neutrophils is phagocytosis of microbes. 2. Eosinophils: About 1 - 5% of leukocytes. The function of eosinophils is detoxification of foreign proteins and other substances. 3. Basophils: 0-1% of leukocytes. Cytoplasmic granules contain mainly heparin and histamine. Heparin is an anticoagulant which prevents blood clotting. -Histamine which is responsible for allergy. II. Agranular leukocytes (Agranulocytes): They do not contain cytoplasmic granules. They include: 1. Monocytes: About 1-6% of the leukocytic count. Monocytes form macrophages, which are large highly phagocytic cells. 2. Lymphocytes: They represent 20-40% of leukocytic count. They are of 2 types T and B-lymphocytes. Lymphocytes are responsible for specific immunity. 21  BODY DEFENSE MECHANISMS (IMMUNITY) Definition: It is the ability to defend pathogenic agents that may cause diseases. Immunity may be non-specific or specific. A. Natural (Non-Specific) Immunity: This type of immunity does not depend on the type or nature of the harmful substance. It includes the following: 1- Skin and mucous membranes. 2- Acid secretion of the stomach. 3- Certain substances in the blood that attach to foreign organisms and toxins and destroy them. 4. Non specific cellular mechanism: -Microphages: →neutrophils & Eosinophils. -Macrophages:→monocytes & tissue macrophages: act by phagocytosis & produce cytokines. -Natural killer cells (NK cells) 1. Non T non B lymphocytes. 2. Large lymphocytes. B. Acquired (Specific) Immunity: This type of immunity is specified to a certain type of pathogens, and does not develop until after the body is first attacked by a certain pathogen (a microbe or a toxin). There are 2 types of acquired immunity. 1. Humoral (B-cell or antibody-mediated) immunity: The B-lymphocytes are activated into plasma cell which secretes antibodies that are specialized to attack the invading agent. Mechanism of Humoral lmmune response: Plasma cell formation and immunoglobulin secretion: Once the B-lymphocytes bind the specific antigen, they become activated, enlarge, proliferate and differentiate into plasma cells. 22  Plasma cells are active cells with expanded rough endoplasmic reticulum producing antibodies at a rapid rate. Formation of memory cells: Some of activated B-lymphocytes do not differentiate into plasma cells but forms memory cells. Memory cells are responsible for the more vigorous response that occurs on a second exposure to the same antigen, the secondary response. Structure of immunoglobulins (antibodies): Immunoglobulins (Ig) are the circulating antibodies formed as a result of B-cell activation by an antigen. Igs molecule is Y shaped and consists of two identical light chains (L) and two identical heavy chains (H) held together by disulphide bonds that permit mobility of the molecule. Types of antibodies: Immunoglobulin G (IgG): It constitutes about 75 % of the antibodies of normal person. It produces a major antiviral, antibacterial and antitoxic activity. 23 It has low molecular weight, thus it can cross placenta to reach fetal blood and is responsible for the passive immunity given to the fetus from the mother. Rh antibodies are of IgG type. Immunoglobulin M (IgM): It is produced in large amounts in the primary response. It does not cross placenta. ABO blood groups antibodies are of IgM type. Immunoglobulin A (IgA) (secretory immunoglobulin) It is the main antibody in the secretions as tears, saliva, and breast milk, and so it has localized protection in external secretions. It plays an important role in first-line defense at mucosal level against viral infection. Immunoglobulin D (IgD): It is present as an antigen receptor on B lymphocytes. It is responsible for antigen recognition by these B cells. Immunoglobulin E (IgE): It is important in parasitic infestations and some allergic responses. It has a role in degranulation and release of histamine, heparin and Leukotriens from basophils and mast cells. 2. Cellular (Cell-mediated or T-cell) immunity: By formation of activated T-lymphocytes that are specifically designed to destroy the pathogenic agent. Cell-Mediated Immunity: 1. On exposure to antigen, specific T lymphocytes are activated. 2. Memory T- lymphocytes are formed leading to rapid response on second exposure to same Ag i.e. secondary response. Types and functions of activated T-lymphocytes: They are classified according to cell surface markers or functional activity into: 1-Helper T-lymphocytes (Th)-CD4: a- They are the most numerous cells b- They recognize the Ag accompanied by MHC-II. 2- Cytotoxic T- lymphocytes (TC)-CD8: a- They recognize Ag accompanied by MHC-I b- Any pathological protein will be presented with MHC-I & stimulate TC. 24 c- Functions: - They are direct attack cells & secrete hole-forming proteins called perforins that produce holes in target cells. - They are important defense against viral infection & cancer cells. - They are responsible for rejection of transplants of foreign tissues & delayed allergic reactions. 3- Suppressor T–lymphocytes (Ts)-CD8: Functions: - Suppress activities of both B & T lymphocytes to provide an important negative feedback mechanism. 25 Respiratory System 26  Respiration Respiration is divided into external respiration & internal respiration I-External respiration: 1. Pulmonary ventilation. 2. Exchange of oxygen and carbon dioxide. 3. Transport of oxygen & carbon dioxide between the lungs and body tissues by the blood. 4. Exchange of oxygen and carbon dioxide between blood and tissues by diffusion. II-Internal respiration: Use of oxygen within mitochondria to generate ATP by oxidative phosphorylation & production of CO2 as a waste product. Non respiratory functions of the lungs: 1. Regulation of acid base balance. 2. Defense against pathogens. 3. Water & heat loss. 4. Increase venous return 5. Enhancing vocalization Air passes from pharynx to trachea to two main bronchi The bronchi repeatedly subdivide within the lungs, becoming smaller and changing in structure, until after 20 generation, the alveoli are reached. The total area of alveoli in contact of capillaries = 100 m2. The airways contain cartilage which gives their shape &support. They are surrounded by smooth muscle to allow change in diameter. Stimulation of vagus & histamine leads to bronchoconstriction. Stimulation of sympathetic leads to bronchodilatation through β2 receptors 27 o The alveoli contain the following cells: a) Type I cells overlying the basement membrane b) Type II cells which secretes surfactant. c) Alveolar macrophages which remove foreign particles inhaled in the lungs Pulmonary Ventilation - Air flows into or out of the lungs because of pressure gradients between the alveoli and the outside air (atmosphere). - The resting respiratory rate is 12-16 cycles/min - Tidal volume is the volume of air inspired or expired each cycle during rest equal 500 cc - Pulmonary ventilation = respiratory rate X tidal volume = 12 X 500 = 6000 c Mechanics of respiration Each respiratory cycle is composed of: 28  a- Inspiration b- Expiration ❖ Inspiration: 1. Inspiration is an active process 2. There is an increase in volume of thorax (increase all dimensions) 3. There is an increase in lung volume as it follows the thoracic wall. 4. There is decrease in intra-thoracic pressure (intrapleural) from - 4 to -6 mmHg 5. There is decrease in intra-alveolar pressure to become – 1mmHg. 6. Air rushes in. The inspiratory muscles are: a. The diaphragm: It is the most important inspiratory muscle. It is supplied by phrenic nerve (3rd to 5th cervical segment). When it descends, it increases the vertical diameter. It is responsible for 75% of the change in chest volume b. The external intercostal muscles: they run obliquely downward and forward from rib to rib. Contraction of external intercostal muscles increases: i. The lateral diameter by elevation of ribs. ii. Anteroposterior diameter by eversion of ribs. c. The accessory inspiratory muscles: contract only with deep (forced) inspiration. They are: i. Sternomastoid which lift the sternum. ii. Anterior serretai which lift many ribs. iii. Scaleni muscles which lift the first two ribs. ❖ Expiration: 1.Normally, expiration is a passive process. 2.It is due to elastic recoil of lungs & chest wall at end of inspiration 29  3.There is decrease in volume of thorax (decrease all dimensions due to relaxation of muscles) 4. There is decrease in lung volume. 5. Intra-thoracic pressure increases to -4 mmHg 6. Intra-alveolar pressure increases to +1 mmH 7. Air forced out 8. Expiration becomes active: i. During forced expiration ii. In conditions of bronchial obstruction e.g bronchial asthma In such conditions, the expiratory muscles contract. Expiratory muscles are: a. Internal intercostal muscles which run obliquely downward and backward from rib to rib so, they pull ribs downward. b. Abdominal muscles which when contract it increase intra- abdominal pressure and push diaphragm up. INSPIRATION EXPIRATTION Inspiration : active process Expiration : passive Thorax volume increase Thorax volume decrease Lung volume increase Lung volume decrease Intra pleural pressure decrease Intra pleural pressure increase Intra alveolar pressure decrease Intra alveolar pressure increase Inspiratory muscle Expiratory muscle - diaphragm only during forced expiration -external intercostal muscle internal intercostal muscle - accessory inspiratory abdominal muscle muscles > steromastoid > serratus anterior. > scaleni muscles. 30  Respiratory pressures Alveolar pressure: o It is the pressure inside the alveoli during respiratory cycle. o During normal inspiration, intra-alveolar pressure decreases below atmospheric pressure. It becomes -1 mmHg less than atmospheric pressure due to expansion of chest & lungs. So, air rushes in. o During normal expiration, intra-alveolar pressure increases above atmospheric pressure. It becomes +1 mmHg more than atmospheric pressure due to elastic recoil of lung & chest. So, air forces out. o At end of inspiration or expiration, intra-alveolar pressure = 0 mmHg. Intrapleural pressure: o Definition: it is the pressure between the two layers of the pleura i.e. between the visceral pleura and the parietal pleura. The intra-pleural space contains few cc of lymph for lubrication of movements. Normally, it does not contain air. During normal respiration, the intra-pleural pressure is Negative due to continuous tendency of the lungs to recoil inwards against continuous tendency of chest wall to expand outwards. 31 o Causes of negative inta-pleural pressure: The recoil tendency of lung against the expansion tendency of chest wall produce intra pleural pressure negativity 1) Recoil tendency of the lungs: Caused by a) Lung elasticity b) Surface tension of fluid lining the alveoli. 2) Expansion tendency of chest wall. At the end of normal expiration, the chest is compressed; its volume is 2.5 liter while its relaxation volume is 5 liter. So, the chest has a continuous tendency to expand. o Measurement: The intra-pleural pressure measured by intra-esophageal balloon connected to sensitive manometer. o Normal values of intra-pleural pressure (IPP): -At end of normal expiration----→ -4 mmHg -At end of normal inspiration---→ -6 mmHg -With deep inspiration ----------→ -12 mmHg because with deep inspiration there is maximal expansion of lungs --→ maximal recoil tendency--→IPP becomes more negative. -During forced inspiration against opened glottis (Muller’s experiment) --→ IPP becomes -30 to – 50 mmHg. 32  -During forced expiration against closed glottis (Valsalva’s experiment)--→IPP becomes + 50 mmHg. o Functions of Intra-pleural pressure: 1. It prevents lung collapse and allows for lung expansion. 2. It helps respiratory movement (pressure inside alveoli is positive while outside is negative). 3. It helps venous & lymphatic return from extra-thoracic vessels. Trans-pulmonary pressure (transmural pressure): It equals = alveolar pressure minus pleural pressure. It is the distending pressure of the alveoli i.e. the more the negativity of the intra-pleural pressure or the more the positivity of the intra-alveolar pressure the more the lung expansion. 33  Surfactant o Definition: It is a surface active agent, which means that when it spreads over the surface of a fluid, it reduces its surface tension. o Chemical nature: It is a complex nature, its components are: 1- Phospholipids: dipalmitoyl-lecithin 2-Surfactant apoproteins. 3-Calcium ions o Origin: it is secreted by type II alveolar epithelium o Functions: (1)Facilitates lung expansion as it reduces surface tension of the fluid lining alveoli (2)Surfactant prevents the collapse of alveoli during expiration: As the alveolus becomes smaller during expiration, the surfactant concentration is increased reducing surface tension further. (3)Surfactant prevents pulmonary oedema Surfactant deficiency occurs in the following conditions: 1- Respiratory distress syndrome (RDS)[ Hyaline membrane disease] It occurs only in premature infants who usually die at birth from failure of respiration 2- Inhalation of 100% oxygen for a long time or at 2 atmospheric pressure of oxygen as in cardiac surgery. 3- Heavy smokers: the smoke of the cigarette inhibits surfactant secretion. 34  Pulmonary Ventilation Static Lung Volumes & Capacities: (1) Tidal volumes (5) Inspiratory capacity (2) Inspiratory reserve volume (6) Functional residual capacity (3)Expiratory reserve volume (7) Vital Capacity (4)Residual volume (8) Total Lung Capacity (A)Lung Volumes: 1. Tidal volume (TV): it is the volume of air inspired or expired each respiratory cycle during rest = 500 cc. 2. Inspiratory reserve volume (IRV): it is the maximum volume of air which can be inspired by deep inspiration after a normal inspiration. It equals 3000 cc. 3. Expiratory reserve volume (ERV): it is the maximum volume of air which can be expired by forced expiration after a normal expiration. It equals 1100 cc. 4.Residual volume (RV): it is the volume of air that remains in the lungs after forced maximal expiration. It equals 1200 cc. i.e. it cannot be expired. It can be expelled after opening the chest to allow the lung to collapse completely. (B) Lung capacities: more than one volume 35 1. Inspiratory capacity (IC): it is the maximal volume of air that can be inspired by deep inspiration after normal expiration It equals TV + IRV = 3500 cc 2. Functional residual capacity (FRC): it is the volume of air remaining in the lung after normal expiration (i.e. at the resting expiratory level). It equals ERV + RV = 2300 cc 3. Vital capacity (VC): it is the maximal volume of air that can be expired by a maximal expiration following a maximal inspiration It equals IRV + ERV + TC = 4600 cc 4. Total lung capacity (TLC): it is the maximal volume of air present in the lung after a maximal inspiration. It equals IRV + TV+ ERV + RV= 5800cc All pulmonary volumes and capacities: - 10 % less in females than in males - Greater in athletes. - Less in recumbent than in standing position - Can be measured by 2 ways: o By the spirometer: it can measure tidal volume, inspiratory reserve volume, expiratory reserve volume, inspiratory capacity and vital capacity. o By Dilution method: it can measure the residual volume, functional residual capacity and total lung capacity. Residual Volume (RV) o Definition: it is the volume of air remaining in the lung after maximal expiration o Measurement: Dilution principle o Normal value : 1200 ml o Significance of residual volume: 1. Physiological: a-It maintains aeration of blood between breaths b-It prevents marked changes in the concentration of CO2 and O2 with each respiration. 36  2. Clinically: The ratio between the residual volume and total lung capacity is normally less than 30%. In diseases that make expiration difficult as in bronchial asthma and emphysema, the residual volume increases and the ratio rises above 30%---→70%. 3. Medico legal: RV can be expelled by opening the chest wall. When the chest wall is opened and the lung is allowed to collapse, however, the lungs still contain some air (minimal air). Minimal air: it is the volume of air (few ml) remaining in the lungs after opening the chest and complete collapse of lungs. It is sufficient for floatation of lungs in water. It is absent in babies born dead. Thus, their lungs sink when put in water. While in babies born alive and then killed, their containing minimal air, so, they float in water. Vital Capacity (VC) o Definition: it is the maximal volume of air that can be expired after a maximal inspiration = IRV + TV + ERV o Measurement: by respirometer o Normal standard: 4600 In males: 2.5 liters/square meter In females: 2 liters/square meter o Significance: It indicates the strength of respiratory muscle and lung elasticity and it determines the ability of the person to perform hard work. So, it can be taken as a measure for physical fitness. Factors affecting vital capacity: A) Physiological factors: 1. Increases in athletes because chest muscles are well developed →more distension of chest---→more distension of lungs---→more air comes in ----→ more vital capacity. 37  2.decreases in females, old age, pregnancy and recumbent position, which prevent descent of diaphragm B) Pathological factors: it is decreased in : a. Chest wall diseases: 1. Muscles: paralysis or myositis 2. Bones: fracture ribs, kyphosis, or scoliosis b. Lung diseases whether: 1. Obstructive e.g. bronchial asthma 2. Restrictive e.g. pneumonia c. Increase amount of blood inside the lung: In left sided heart failure, there is pulmonary congestion which gives less space for air--→decrease air reaching-→decrease lung capacity. d. Diaphragm: Any condition that interferes with free descent of diaphragm will decrease the VC e.g. enlarged liver or spleen. Dead Space (DS) o Definition: the air passage which does not share in gas exchange with blood. o Types: 1- Anatomical dead space (the conducting zone): air passages from nose to pharynx to trachea to bronchi to bronchioles down to respiratory bronchioles, because of their thick wall. 2- Alveolar dead space: some alveoli not undergo gas exchange because they have no blood supply. 3- Physiological dead space = anatomical DS + alveolar DS -Under normal conditions: Physiological dead space = anatomical DS because all alveoli are functioning Normal values = 150 – 167 ml = 30% of tidal volume Vagus leads to broncho constriction i.e. decrease dead space 38  While sympathetic supply leads to broncho dilatation i.e. increase DS o Significance: (1) In each respiration: 500 cc of air are taken 350 cc enter the alveoli (alveolar air) & Undergo gas exchange with blood while 150 cc remain in DS. (2) It protects alveoli against damage: It warms, filters and moistens the inspired air Particles with a diameter more than 10 microns are caught in nose hairs, stick to mucus of nose while particles with diameter 2 – 6 microns stick to the mucus of trachea & bronchi. These particles are then expelled by cough and sneeze reflexes and the movements of the cilia. Particles less than 2 microns are removed by phagocytic cells in alveoli. Particles less than 0.3 microns remain in the air phase in the alveoli and are breathed again. o Measurement: 1-Fowler method 2- Bohar method 39  The respiratory functions of blood Gas exchange between alveolar air & venous blood occurs by simple diffusion. Respiratory membrane is formed of the following layers: 1. Fluid lining alveoli and surfactant 2. Alveolar epithelium 3. Epithelium of basement membrane 4. Interstitial space containing fluid 5. Capillary basement membrane 6. Capillary endothelium ❖ Factors affecting diffusion of gas through the respiratory membrane: Diffusion is directly Diffusion is inversely proportional with proportional with Pressure gradient between alveoli Square root of molecular weight air and venous blood Surface area of pulmonary Thickness of pulmonary membrane membrane Temperature Diffusion coefficient 40  Hypoxia ▪ Definition: Oxygen deficiency at tissue level. It may be due to decrease O2 supply or decrease O2 utilization ability. Anoxia: complete absence of oxygen. ▪ Hypoxia is divided into four types: 1- Hypoxic hypoxia: in which PO2 of arterial blood is reduced. 2- Anemic hypoxia: in which PO2 of the arterial blood is normal but the amount of Hb available to carry O2 is reduced. 3- Stagnant (ischemic) hypoxia: in which PO2 in arterial blood is normal & Hb is normal but blood flow to tissues is low. 4- Histotoxic hypoxia: in which PO2 in arterial blood is normal, Hb is normal & blood flow is normal but due to toxic agents, tissue cells cannot utilize O2. Cyanosis Definition:it is bluish coloration of skin & mucous membranes due to presence of excess reduced hemoglobin in capillary blood Threshold for cyanosis: 5 gm reduced HB/100 ml capillary blood. Reduced Hb has blue color seen in lips, mm, nail beds, and ear lobules. Types: 1) Generalized (or central) cyanosis 2) Localized (or peripheral) cyanosis. 41 Nerve 42  Nerve The function of nerves is to carry messages to & from central nervous system. The unit of structure of the nervous system is neuron which is specialized for rapid transfer & integration of information. ❖ Neuron: It is formed of cell body & cell processes ▪ The cell body (Soma): -It is surrounded with cell membrane. It contains cytoplasm & nucleus. -Cytoplasm contains mitochondria, Golgi apparatus, endoplasmic reticulum, pigment, fat, glycogen, neurofibrils & Nissil granules which are rich in ribose nucleic acid (RNA) and play an important role in metabolism of cell. ▪ The processes: The dendrites: short branches which receive the ingoing impulses. The axon or nerve fiber which is a long process of the cell & usually carries impulses from the nerve. It is surrounded with the plasma membrane which is a continuation of cell membrane. It ends in a number of synaptic knobs which contain vesicles rich in chemical transmitters. 43 Two types of nerve fibers are found: (a)Myelinated nerve fibers: ❑ The axon is surrounded by a myelin sheath, made by Schwann cells, (important for rapid conduction of nerve impulse) & outer neurolemmal sheath (important for regeneration of axon). ❑ The myelin sheath is highly insulator to electric currents. It does not form a continuous layer, but is interrupted at intervals of 1 mm called “Nodes of Ranvier” which are uninsulated area. (b) Non-myelinated nerve fibers: The myelin sheath is absent. Excitability: -It is the ability of living tissues to respond to changes in environment. -The most excitable tissues in the body are nerves & muscles. ▪ Stimulus: It is the change in the environment. ▪ Types of stimuli: Electrical – mechanical – chemical – thermal Electrical stimulus is preferred because: 1/It is similar to natural stimuli inside the body. 2/It can be controlled. 3/It can be accurately measured. 4/It leaves the tissue undamaged. ▪ Method of nerve stimulation: For electrical stimulation of nerve: 2 stimulating electrodes are put on surface of nerve fiber: One connected to anode of stimulator & the other is connected to cathode of same stimulator. The important element is the cathode which induces flow of current *Conductivity: Is the ability of nerve fiber to propagate impulse. 44  Resting Membrane Potential ▪ Definition: It is membrane potential difference between inside and outside the nerve at rest. (i.e. No excitation). It is found in all cells but more marked in nerve cells & muscle cells. ▪ Measurement: - Two microelectrodes are used: One electrode is placed on surface of fiber membrane & the other is dipped inside the fiber. -RMP = - 90 mv in large nerve & skeletal muscle fibers. = - 70 mv in medium size neurons = -20 to – 40 mv in RBC & epithelial cells. ▪ RMP is caused by: ▪ 1- Selective permeability (form the majority of resting membrane potential). 2- Sodium – potassium pump. 45 I - selective permeability: 1- K+ is the main ion intracellular. 2- Na+ is the main ion extra cellular. 3- K-Na leak channels are present in membrane allowing movement of both Na and K. 4- K+ is present 35 time inside than outside 5- Na+ is present 10 times outside than inside. 6- K+ outflow is much greater than Na+ inflow (100 times) because of: smaller size of K+ than Na+ and high concentration gradient of K+. 7- Net effect is increase +ve charge outside and –ve charge inside. II – Sodium –potassium pump: - Is active and needs ATP - Na - K pump is a carrier protein in the cell membrane with three characters:- 1. It has three binding sites on the inside for Na+. 2. It has two binding sites on the outside for K+. 3. The inner part has ATPase activity. - Na is actively transported out of cell. - K is actively transported into cell. - The out ward pumping of 3Na+ is accompanied by inward pumping of 2K+. N.B if the RMP = -90 mv the selective permiability form -86mv while sodium potassium pump = -4 mv 46  Action potential It is rapid change in membrane potential due to stimulation of nerve fiber by adequate stimuli. I - Ionic change During rest: membrane potential = -70 mv. Application of stimuli: These stimuli must be threshold to stimulate the nerve. Stimulus artifact which is small oscillation indicates time of application of stimuli. Latent period: This is period between applications of stimuli and beginning of response. 1. Partial depolarization where membrane potential decrease to -55 mv due to opening of some voltage gated Na channels and entry of Na +. 2. Firing level at -55 mv all Na channels are opened. 3. Complete depolarization: where membrane potential decrease then lost then reversal of polarity occur to (+35 mv) due to opening of all voltages gated Na channels and entry of Na. 47 4. Repolarization phase where membrane potential return to resting due to inactivation of Na channels and opening of K channels. Repolarization process starts rapid then when 70% completed it slow down. (Repolarization is due to K exit). 5. After depolarization: membrane potential become below resting level caused by K exit and slow closure of K channels. 6. After hyper polarization: membrane potential return to resting level by Na – K pump. NB: step 5 & 6 collectively known as hyperpolarization. 48 II - Excitability change: Absolute refractory period the nerve dose not respond to any stimulus in this period, this period coincide with depolarization phase and first one third of Repolarization. Relative refractory period: the nerve show weak response in this period. It coincides with second and third part of Repolarization. It's occur due to recovery of some Na channel. Depolarization Repolarization Membrane potential decrease. Membrane potential return to rest. Composed of:- partial depolarization. Composed of: -Rapid part. - complete depolarization Slow part. Ionic change opening of Na channels. Ionic change opening of K channels. Form : ascending limb. From: descending limp. Excitability lost. Increase gradually. 49 Propagation (conduction) of action potential: The conduction of AP differs whether the nerve is myelinated or not. In unmyelinated nerve there is local circuit of current flow between the depolarized area and adjacent resting area lead to its depolarization while in myelinated nerve because myelin sheath is insulator the action potential jump at node of Ranvier. Action potential travels along the length of the nerve fiber in both directions. Propagation in unmyelinated axons: Passive ❑ A local circuit of current flow occurs between the depolarized area of the membrane and the adjacent resting areas i.e. positive charges flow passively to area of negativity on both outer & inner surface of the membrane. ❑ The adjacent areas become depolarized to firing level producing action potential and so on. ❑ The action potential propagated passively with same magnitude. 50  ❑ The propagation speed  square root of fiber diameter. Propagation in myelinated axons: salutatory conduction ❑ Propagation in myelinated axons follows same principle of propagation in unmyelinated ones. But: because the myelin sheath is insulator, the action potential generated only at nodes of Ranvier and the positive charges jump from resting nodes to activating ones (Salutatory conduction). 51