Blood, Nerve & Muscle Functions PDF

The cell: Def: it is the basic structure of the body it is surrounded by cell membrane it is formed of *cytoplasm *nucleus The cell membrane: -it is very elastic -surround the cell -separate the intra cellular fluid (ICF)from the extra cellular flui...

The cell: Def: it is the basic structure of the body it is surrounded by cell membrane it is formed of *cytoplasm *nucleus The cell membrane: -it is very elastic -surround the cell -separate the intra cellular fluid (ICF)from the extra cellular fluid (ECF) -it is semipermeable (allow some substances to pass and others not pass) -it is made of *protein (mainly 55%) *phospholipid & carbohydrates  Function of cell membrane protein: 1-structure of cellmembrane (structural proteins) 2-act as channels for water, and ions 3-act as pump for active transport of ions (pump ions against concentration gradient whether into cell or out of it) 4- act as receptors for hormones and chemical transmitters 5-act as enzymes to catalyze (make it rapid) the reactions 6-act as intercellular connections 7-identity proteins  Total body water 60% of body weight in adults 75% of body weight in infants 60% water 40% intracellular 20% extracellular *Inside cell *out side cell *Main cation +ve—K+ *main cation +ve—Na+ *Mg++ is high *Ca++ is low  Method of transport across cell membrane: 1-simple diffusion: Passage of MOLECULES from high concentration of molecules to low concentration of molecules *rate of diffusion is directly proportional with -concentration gradient (the more the concentration the more the diffusion) -surface area (the more the surface area the more the diffusion) -temperature -solubility of the substance *simple diffusion need no energy & no carrier  2-facilitated diffusion: -it is the transport of the molecules from high concentration to low concentration but the molecules are large in size so they need carrier to carry them but no need for energy -the carriers needed in facilitated diffusion are *specific: (there is carrier for each kind of molecules not used for other kind) *have the saturation property: the diffusion stops when all carriers are fully saturated NB: *if molecule X have same structure as another molecule Y and they try to pass through same membrane , they may compete with for the same carrier and facilitated diffusion may stop (competitive inhibition) *facilitated diffusion is affected by temperature  3-Active transport: Passage of MOLECULES from low concentration of molecules to high concentration of molecules -against concentration gradient -need energy -need carrier -need enzymes -Affected by temperature -has the same saturation property & competitive inhibition  4-Osmosis : It is the passage of H2O from high concentration of WATER to low concentration of water through semipermeable membrane. *along concentration gradient (from high to low) 5-vesicular transport: *Cell engulf particles *large substances come in contact with cell membrane *cell membrane invaginate around substance *substance enter inside cell *it is either phagocytosis or pinocytosis  Function of blood: 1-Transport function: O2, CO2, glucose, hormones 2-Defensive function: by White blood cells form antibodies 3-Homeostatic function: the blood help to keep internal environment constant 4-Hemostatic function: stop bleeding when blood vessel is injured  Composition of blood: 45% Cells 55% plasma 1-RBCs 5 million/cmm *clear yellow fluid 2-WBCs 4000-11000/cmm *Formed of: 3-Platelets 250000/cmm 1-water 2-gases O2, CO2 3-organic substances *plasma proteins 7 gm /dl *lipids, hormones, glucose * 4-inorganic substances *Na+,CL-,K+,HCO3-  Plasma proteins: Def: they are proteins in the plasma 7 gms/dl They are 1-Globulin 2.5gm/dl *50% formed in liver *50% formed in RES (Reticuluendothelial system) 2-Fibrinogen 0.4gm/dl *Formed in liver ONLY 3-Prothrombin 0.01gm/dl *Formed in liver ONLY 4-Albumin 3.5-5gm/dl *Formed in liver ONLY  Albumin /Globulin ratio: A/G ratio Def: it is the ratio between the Albumin and Globulin concentration in the blood. The normal A/G ratio is 1.2---1.6 The A/G ratio may decrease in 1-liver disease----due to decrease Albumin 2-Kidney disease—due to increase loss of Albumin 3-infection---due to increase formation of globulin  Function of plasma proteins: Specific function Non Specific function 1-Albumin—Responsible for formation of 1-*plasma proteins act as CARRIERS for THE EFFECTIVE OSMOTIC PRESSURE of substances----carry VITAMINS , plasma----due to high concentration. HORMONES,& IRON. (ADSORPTION *Effective osmotic pressure = 28mmHg FUNCTION). 2-Globulins-----they are 3 types 2-*plasma proteins act as BUFFER *Alpha , Beta ---transport proteins action.(Keep the PH of the blood constant). *Gamma-----form antibodies---(Defensive function). 3-Fibrinogen---form viscosity of plasma(1.5 3-*plasma proteins close the PORES in the times as water). wall of the capillaries------limit their 4-*Fibrinogen & Prothrombin---needed for permeability blood clotting. 4-Diet reserve:---the plasma proteins act as source to replace tissue proteins.  Erythrocytes: help flexibility of cell *biconcave discs increase surface area *Non nucleated *7 microns in diameter *5.5 million/cmm in Male *4.8 million/cmm in Female *Life span 120 days. *surrounded by semipermeable membrane. *contain _ Hb 34% of its weight. _ K+, & carbonic anhydrase enzyme *NO mitochondria  Hemoglobin: (Hb). Def: it is the red pigment which carry oxygen. * 15-16 gm/dl in Male 13-14 gm/dl in Female 19 gm/dl in infants Function of Hb: 1- Carry O2, CO2 2- Buffer action (Keep PH of blood constant).  Erythropoesis: Def: process of formation of RBCs Site of formation of the RBCs: *Fetus-------------------- in liver & spleen *Children---------------- in bone marrow of all bones *Adults------------------- ends of long bones *over 20 years---------- in membranous bones (sternum)  Factors affecting erythropoesis: 1-oxygen supply to tissues 2-healthy liver 3-healthy kidney 4-healthy bone marrow 5-hormones 6-diet  1- Oxygen supply to tissues: Hypoxia (decrease O2 supply to tissues) +++++ RBCs formation Causes of hypoxia: *decrease O2 tension---high altitudes increase demand *hemorrhage---decrease RBCs *heart diseases *lung diseases  Mechanism: Hypoxia (decrease O2 supply to tissues) Liver15% Kidney 85% Erythropoetin hormone +++ Bone marrow +++ RBCs formation  Factors affecting Erythropoetin secretion: Erythropoetin hormone is secreted due to: *hypoxia *androgen *alkalosis *catecholamines *adenosine , cobalt  2-healthy liver: The liver forms----*15% of Erythropoetin * store iron, & vitamin B12 3- healthy kidney: The kidney forms----*85% of Erythropoetin 4-healthy bone marrow: It is the site of formation of RBCs Destroyed by: *x-Ray, atomic radiation, drugs, tumors 5-hormones:there are hormones which +++ erythropoesis as: *Erythropoetin *Thyroid hormone *Androgen  6- diet: In order to form RBCs normally the diet should contain---*vitamin B12 , folic acid *iron , & cobalt  Vitamin B12 & Folic acid: Cyanocobalamines, Maturation factor Extrensic factor Function of vitamin B12 in RBCs formation: *needed for DNA formation *needed for cell division *needed for RBCs maturation *needed for myelin sheath formation of nerves  Decrease vitamin B12 may lead to: *failure of DNA formation *failure of cell division *failure of RBCs maturation *failure of myelin sheath formation *RBCs increase in size ----form megaloblastic anemia-------*large RBCs *oval *short life span  Handling of vitamin B12 by the body (absorption): *Vitamin B12 is present in liver , meat , chiken *Daily needs are minimal HCL—may break vit. B12 intrensic factor cover vit.B12 protect it from HCL Absorbed from lower ileum And carried on transcobalamin Stored in liver  Intrinsic factor: *glycoprotein *secreted by parietal cells of fundus & body of stomach *cover vitamin B12 & protect it from HCL Defeciency: its deficiency may lead to MACROCYTIC ANEMIA  Iron. Function of iron in erythropoesis. *daily needs of iron 0.6mg/day Iron in food in Ferric form Fe+++ (not absorbed) HCL + Vitamin C Ferrus Fe++ (absorbed) (from upper small intestine by the use of Apoferritin (iron carrying protein))---in blood iron is carried on Transferrin(iron transport protein) to bone marrow Iron is stored as ----FERRETIN  Defeciency of iron may be due to : -decrease intake -decrease absorption -chronic blood loss This leads to microcytic hypochromic anemia  Anemia. Def: decrease number of RBCs Hb content OR both. Anemia is considered to be present: RBCs number less than 4.5 million/cmm in male RBCs number less than 3.9 million/cmm in female Hb content less than 13.5 gm% in male Hb content less than 11.5 gm% in female  Blood indices: *MCH (Mean corpuscular Hb): Def: amount of Hb in single RBC MCH = Hb * 10/RBCs count in million 15 * 10/ 5-------= 30 picogram *Mean corpuscular volume (MCV): Def: volume of a single RBC MCV = haematocrite * 10 / RBCs count in million 45 * 10/ 5 = 90 cubic micron  Classification of anemia: Normocytic Microcytic Macrocytic Normochromic Hypochromic Hyperchromic *Normal size *Decreased *Increased size RBCs size RBCs RBCs *Normal Hb *Decreased *Increased Hb in Content in each Hb in each each RBC. RBC RBC  Normocytic normochromic anemia: Causes of normocytic normochromic anemia: 1-Aplastic anemia 2-hemorrhagic anemia 3-acute blood loss 1-Aplastic anemia: The bone marrow fail to form RBCs due to bone marrow depression. This may be due to: *antibiotic *tumors *radiation  2-Hemolytic anemia: Excessive hemolysis of RBCs ----lead to decrease in RBCs number. This may be due to: Intrinsic causes: causes in the RBCs itself. *spherocytosis----the RBCs have sphere shape (disorder in membrane) cell membrane is fragile on entry in narrow blood vessel they got broken (hemolysis)  * Sickle cell anemia: The RBCs contain abnormal Hb—HBs On decrease O2 tension RBCs are hemolysed  *(G-6-P-D) defeciency: (favism) Glucose 6 phosphate dehydrogenase enzyme defeciency. RBCs are usually exposed to oxidizing agents as (beans,& aspirin) this lead Hb to be oxidized the enzyme G6PD reduce Hb and return it to normal and protect it (defend RBCs against oxidants) If G6PD enzyme is decreased or defecient on exposure to oxidizing agents (beans, aspirin ) RBCs hemolysis  Extrensic disorders: 1-hemolysis of RBCs due to incompatible blood transfusion. 2-bacterial toxins 3-drugs as antibacterial 4-chemicals 3- Acute blood loss: Loss of large amount of blood in small amount of time.  Causes of Microcytic Hypochromic anemia: Causes of Iron defeciency. 1- decrease iron in diet as in starvation 2- increase demand as in pregnancy. 3-decrease iron absorption as in: *decrease vitamin C *gastrectomy *intestinal disease *increase phosphate and phytate-----form large compound with iron -----insoluble 4-Chronic blood loss: Loss of small amounts of blood for long time as in: *ankylostoma ,bilharzia , 5-increase Tannic acid ----decrease iron absorption  Causes of Macrocytic Hyperchromic anemia: 1- vitamin B12 defeciency. 2- folic acid defeciency Both Lead to decrease DNA formation & Failure of maturation of RBCs  Causes of vitamin B12 deficiency: 1-Rare to be deficient in diet as its daily needs are minimal. 2-liver disease------------no storage of vitamin B12 3-defecient absorption----- in intestinal disease. In gastrectomy (defecient intrensic factor).  Causes of folic acid deficiency: 1-decrease intake. 2-increase demand ---as in pregnancy. 3-decrease absorption---intestinal disease. 4-cancer drugs---interfere with formation and absorption of folic acid  Pernicious anemia: *familial disease *common in woman than males *autoimmune disease *there are antibodies against parietal cells secreting intrensic factor------this lead to decrease intrensic factor or its absence-------- *deficient vitamin B12----Macrocytic hyperchromic anemia.  Treatment of anemia: *treat the cause *iron by mouth in iron deficiency *iron injection in severe cases *vitamin B12 injection in pernicious anemia *folic acid *Blood transfusion in severe cases.  Polycythemia: Def: increase number of RBCs Types: 1-primary polycythemia (polycythemia vera)-------------due to tumor in bone marrow 2-secondary polycythemia---in cases of hypoxia Effects of polycythemia: *increase blood viscosity----decrease venous return *increase blood pressure *cyanosis ----due to increase reduced hemoglobin  Hemostasis: Def: prevention of blood loss after injury. It carried by 3 mechanisms Vascular platelet stabilize platelet spasm reaction plug by fibrin Vasoconstriction form platelet form blood clot Of blood vessles plug *weak *temporary  Platelets: *300000/cmm in number *formed in bone marrow *the membrane contain PF3 needed for clotting Platelet function: *platelet adhesion *platelet activation *platelet release *platelet aggregation *platelet procoagulant activity *platelet fusion  1-platelet adhesion: injury platelets adhere to exposed collagen under endothelium clotting factor Vlll (von willbrand factor) help adherence glycoprotein cover help adhesion 2-platelet activation: The platelets ---swell form pseudopodia discharge their granules The activation of platelets depends on *ADP *thrombin *collagen  3-Platelet release: *the platelets release ---- Serotonin make platelets sticky *the platelets release----thromboxane A2 +++ platelet aggregation cause vasoconstriction *the platelets release --- ADP stimulate aggregation  4-platelet aggregation: The membranes of the adjacent platelets adhere to each other. Aggregation Helped by inhibited by 1-ADP 1-Aspirin(used to 2-Thromboxane A 2 prevent thrombus)  5- platelet procoagulant activity: the membrane phospholipid is exposed (platelet factor -3) form surface for the coagulation factors of plasma to concentrate on start blood coagulation  6- platelet fusion: Platelets fuse together at site of injury-----this is helped by ADP.  Blood coagulation: *The blood clott is formed of -fibrin -blood cells -platelets -plasma *the clotting factors are present in the plasma in an inactive form *the clotting factors become activated on cut wound to form blood clot *the clotting factors are 12 (1-13) no factor Vl *the clotting factors are activated by---intrinsic , extrensic pathway  Intrinsic pathway: Wound Negative charges Xll------------Xll(a) Xl---------Xl(a) lX--------lX(a) Ca++,Vlll X----------X(a) V,PL,Ca++ prothrombin-------thrombin fibrinogen------fibrin Ca++,Xlll---fibrin tight  Extrinsic pathway: injury of tissue release tissue thromboplastin Vll---------Vll(a) Ca++, PF-3 X-------------X(a) V,Ca++,PL prothrombin------thrombin fibrinogen-------fibrin Ca++, Xlll fibrin tight  Intrinsic pathway: *All factors involved are present in the blood. *It begins by activation of factor 12 either by: Invivo----Exposed collagen Invitro---expose blood to negative charges *Ca++ is needed to complete the pathway Extrinsic pathway: *need the presence of other factor which arise on injury---(tissue thromboplastin).  Notes: *both systems act together on vessel injury. *Extrensic pathway is much faster (15 sec.) ,while the intrinsic pathway is slower (1-6 min). *the extrensic pathway is more extensive. *Ca++ is needed for all steps of fibrin formation except the first 2 steps. *the loose fibrin formed is transferred to tight fibrin by factor Xlll (fibrin stabilizing factor).  The Anti clotting mechanisms: Mechanisms inside body to prevent blood clot Function: 1-limit the tendency of blood to clot inside body 2-break down the already formed clot Mechanism of anticlotting General Specific 1-smooth vascular endothelium 1-Antithrombin III *not suitable for formation of clot -Present in blood -it inactivate clotting factors IX,X,XI,XII 2-liver remove the active clotting factors and 2-prostacyclin inactivate them -it inhibit platelet aggregation 3-Heparine 3-fibrinolytic system 4-protein C & protein S -inactivate factors V, VIII -increase plasmin formation -inhibit the INHIBITOR of tissue plasminogen activator  The anticlotting mechanisms Physiologic limitation of blood coagulation. Def: they are the mechanisms which limit blood coagulation inside the blood vessles. General mechanisms specific mechanisms 1-liver---remove activated 1-fibrinolytic Coagulation factors system 2-smooth endothelium *plasmin Prevent activate factor Xll *protein C 3-rapid blood flow Prevent activate factor Xll 2- Antithrombin lll 4-heparine present in blood inactivate IX,X,XI,XII  1-fibrinolytic system: Plasminogen—tissue plasminogen activator plasmin streptokinase (fibrinolysin) Fibrin (fibrinogen) Fibrinolysin fibrin degradation (plasmin) product Fibrinolysin: *active enzyme *cause lysis of fibrinogen & fibrin-------FDP *  Streptokinase (bacterial enzyme) Urokinase (formed by kidney) Used for treatment of myocardial infarction *exercise increase release of tissue plasminogen activator-----help to protect against infarction.  Fibrinolytic system: endothelial cells (not in brain) form thrombomodulin bind to thrombin form complex activate protein C Inactivate factors V, Vlll increase plasmin cause lysis of fibrin to FDP  2-Antithrombin lll: *it is a heparin cofactor *its action is facilitated by heparin *it inhibit activated clotting factors  Anticoagulants: Def: substances used to prevent blood coagulation Invitro anti coagulants invivo anticoagulants Used outside body used inside body  1- invitro anticoagulants: * citrate------in blood bags bind ionized Ca++ precipitate Ca++ inhibit intrensic and extrensic pathways *Oxalate-----precipitate Ca++ *Silicone coated tubes-----prevent activation of factor Xll ------prevent activation of platelets  2-invivo anticoagulants: *heparine , *Dicumarol Dicumarol Heparine source Plant origin In basophil cells mast cells liver Intake Oral IV , IM Onset Slow onset , long duration Rapid onset , short duration Site of action Only invivo Act invivo , & invitro Action Compete with vitamin k for *increase antithrombin lll its receptors in liver----so activity prevent liver to form factors *increase lipase enzyme--- 2,7,9,10 clear blood from lipids Antidote Vitamin K Protamine sulphate  Abnormalities of hemostasis: 1-vitamin K defeciency. *Vitamin K is used by liver to form factors ll ,Vll ,lX ,X *vitamin K is formed by the bacterial flora in the intestine *delay circumcision one month after birth---as the baby new born has no bacterial flora in his intestine so he may bleed due to defecient vitamin K-----defecient coagulation factors ll ,Vll ,lX ,X  Causes of deficiency of vitamin K: *sterile intestine----new born infant long antibiotics intake *anticoagulants---inhibit vitamin K 2-Hemophelia: *heriditary disease *congenital *sex linked recessive *females are usually carriers *affect males  *there are 3 types of Hemophelia: A------deficient factor Vlll` 85% B------deficient factor lX 10% C------defecient factor Xl 5% Symptoms: *There are severe prolonged bleeding on mild & minimal trauma *clotting time is prolonged 3-Thrombocytopenic purpura: *decrease number of platelets below 50000/cmm *there is subcutaneous hemmorrhages---petichae *prolonged Bleeding time.  Blood groups: *The RBCs contain on their surface type of antigen called Agglutinogen *According to this antigen we detect the type of blood group *There are 2 types of Agglutinogen----A , & B A -------------blood group A --------------blood group B B AB ---------------blood group AB ---------------blood group O _  *Plasma contain type of antibodies called Agglutinins *if the antigen (Agglutinogen) meet its antibody (Agglutinins)-----there will occur Agglutination & break (hemolysis )of the RBCs. *for that the plasma contain the agglutinins OF THE ABSENT Agglutinogen on the RBCs  -------------Blood group A------Plasma contain Anti B A B --------Blood group B------Plasma contain Anti A AB ---------Blood group AB----Plasma do not contain antibodies _ ---------Blood group O------Plasma contain Anti A & Anti B  *The RBCs contain on their surface other Antigen beside the A, & B ------this is called the Rh antigen (D antigen) A, Rh *85% of the people contain the Rh antigen on their RBCs and they are called------Rh +ve *15% of the people do not contain the Rh antigen on their RBCs and they are called-----Rh _ve. *The Rh+ve is dominant over the Rh_ve *The Rh+ve & Rh-ve persons have no AntiRh normally in the plasma *The Rh -ve person if given Rh+ve blood will form antibodies (Anti Rh) while the Rh+ve person do not form antibodies (Anti Rh) whether given Rh+ve or Rh_ve blood.  ------blood group A_ve ---plasma contain Anti B A A, -----blood group A+ve ---plasma contain Anti B Rh -----blood group B_ve ---plasma contain Anti A B ----blood group B+ve ---plasma contain Anti A B,Rh A,B, -----blood group AB+ve ---plasma contain ---- Rh -----blood group AB _ve ---plasma contain ---- A,B -----blood group O _ve ---plasma contain Anti A,B -  ----blood group O+ve—plasma contain Anti A,B -,Rh  Importance of blood groups: 1- Medicolegal :)(Desputed paternity). The blood groups can deny paternity (good negative test ) but can not proof it 2- Blood transfusion: Law of blood transfusion: During blood transfusion we consider ONLY RBCs of donor & plasma of recepient Not to make agglutination between them INCOMPATIBLE BLOOD TRANSFUSION occur in *the DONORS RBCs agglutinate with the corresponding ANTIBODIES in the PLASMA OF RECEPIENT *Blood group O----universal Donor as it contain no (No antigen (agglutinogen)) *Blood group AB -universal recepient as it contain no agglutinins (No antibodies) Blood group A----40% Blood group B----10% Blood group AB---5% Blood group O---45%  Importance of Rh : 1-Erythroblastosis foetalis: (Rhesus haemolytic disease of the new born) *Rh+ve male marry an Rh _ve female *the first baby is Rh+ve *during delivery some of the blood of the baby go to the mother *the mother will form Anti Rh against the Rh antigen of the RBCs of the baby *on the second baby he is Rh+ve *the Anti Rh in the mother will cross the placenta to the second baby----meet with Rh antigen on the RBCs of the baby----Agglutination---break RBCs  Agglutination---break RBCs Anemia, jaundice,bile pigments cross blood brain barrier & deposit in brain (Kernicterus) Treatment: 1-Mother ---give the mother within 72 hours of delivery----Anti D injecctions------which prevent the formation & neutralize the Anti Rh antibodies in the mother -----prevent the mother from being sensitized (has Anti D antibodies in her plasma) and so on every delivery 2-baby----if born alive----blood exchange by O_ve blood  2- Blood transfusion: * If Rh_ve person is given Rh+ve blood his body will form Anti Rh (agglutinins) * If this person is given another time Rh+ve blood - -----Agglutination will occur * There for any Rh_ve person should be given Rh_ve blood always, & if he is given Rh+ve blood it should be given once to prevent Agglutination  Notes: The first baby in case of erythroblastosis may be affected IF THE MOTHER IS ALREADY GIVEN Rh+ve BLOOD BEFORE (sensitized) No fetal complication regarding the ABO system blood groups as the antibodies of the blood groups from the type M can not cross the placenta  Complication of incompatible blood transfusion: This lead tohemolysis of the given RBCs this lead to: *clumping of RBCs--block blood vessels—joint pain back pain block coronary vessels—angina *intravascular hemolysis: Lead to: -release of Histamine----VD---- BP----shock -release K+----------arrhythmia -release Hb----billirubin----jaundice block renal tubules----renal failure  White blood cells: *the mobile units of the defensive system *4000-11000/cmm *the WBCs are Granulocytes Agranulocytes *have granules in cytoplasm *have no granules 1-Neutrophils 1-Monocytes 2-Esinophils 2-Lymphocytes 3-Basophils  Function of leucocytes: Esinophils 1-Attack parasites 2-form mediators in Allergy Basophils 1-form histamine-----increase flow of blood---increase antibodies Neutrophils 1-kill bacteria lymphocytes Formed in lymph nodes, spleen, thymus 1-has a role in immunity Monocytes Have ameboid movement-----go to area of inflammation In the tissue ------they form tissue macrophages----form defense  Immunity: Def: Ability of the body to resist microorganisms Antigen: Def: substance can stimulate the immune system Types of immunity Non specific immunity specific immunity *not directed to specific *directed to specific organism organism  Non specific immunity: Characters: 1-rapid 2-not directed to specific organism 3-Innate (no need for previous exposure) 4-it include -mechanical & chemical barriers -non specific cellular mechanisms -non specific humoral mechanisms  1-mechanical & chemical barriers: 1-epithelium ----cover the skin line GIT & respiratory tract 2-mucus----in respiratory tract----trap dust Acid ----from stomach 2-Non specific cellular mechanism: 1-microphages-----neutrophils & esinophils 2-macrophages----monocytes , tissue macrophages form phagocytosis 3-natural killer cells:---lymphocytes (large) can destroy tumor cells can destroy virus  3- non specific humoral mechanisms: 1-lysosomes:----dissolve bacteria 2-interferon:----they are released from virus affected cells -----they kill the virus & cell -----they are alpha, Beta, gamma 3-acute phase proteins: *formed in liver *during acute inflammation *during tissue distruction *they are C reactive proteins  4-properdin system: Complex system of protein ---- can activate complement 5-complement system: 11 plasma protein enzymes (C1-C9) they mediate humoral and cellular immunity  II- specific (Aquired immunity): Def: it is the ability of immune system to respond to foreign antigen. *the specific (aquired) immunity is divided into Humoral immunity cell mediated immunity *involve B lymphocytes *involve T lymphocytes *form antibodies *major defense against *major defense against virus, fungs, allergy, Bacteria & tumors &reject transplants Humoral immune response: Mechanism: B lymphocytes detect antigen by antibodies on their surface When they detect the antigen They change to plasma cells plasma cells form antibodies memory B cells act on second exposure of same antigen and produce secondary response NB: the secondary response is more rapid and more potent than primary response Primary response Secondary response -follow initial exposure to antigen -occur on second exposure of same antigen -the antibodies start to appear in plasma after -concentration formed is much higher than 8 days first time -reach high level in few weeks then decrease -antibodies formed are igG -the antibodies formed are IgM  Antibodies:---gamma globulins immunoglobulins Types of antibodies: Immunoglobulins Ig M, A, G, E, D IgA----in body secretions protect against infection Act against virus IgE----play role in allergy act on parasitic infection IgD----present on B lymphocytes detect antigen  IgG---lowest Mw highest concentration cross plasenta Rh antibody secondary response IgM---highest Mw lowest concentration ABO blood group not cross plasenta primary response  Function of antibodies: They bind to antigens----& destroy them by: *agglutination *neutralization *activate natural killer Antigen : Def: any substance that can stimulate immune system  Cellular immunity: On exposure to antigen T lymphocytes are activated Types of T lymphocytes: 1-T helper cells CD4: -most numerous -detect antigen -stimulate cytotoxic cells to attack antigen -secrete interferon  2-cytotoxic T lymphocytes CD8: -they secrete hole forming proteins (perforins) -defend against virus -they reject transplants 3-suppressor T lymphocytes: -suppress T, B lymphocytes  Inflammatory response: Def: response of the living tissue to infection , trauma , or chemicals -There will be vasodilation of blood vessles and this leads to reddness , hottness and accumulation of fluid ( edema )  Steps of the inflammatory response : 1-Migration : The WBCs stick to the inflammed capillary wall 2-Diapedesis: The WBCs squeeze themselves through the capillary pores 3-Ameboid movement : The WBCs move by ameboid movement through wall of vessels to tissue to reach the bacteria 4-Chemotaxis : Positive chemotaxis Negative chemotaxis -attract the WBCs by bacterial Repulsion of WBCs away from toxins bacteria  5-Oppsonization : Prepare the bacteria to be easily phagosytosed The oppsonins are the IgG , complement proteins 6-Phagocytosis: -bacteria is phagocytosed then act on by lysosomes NB: Leucocytosis : increase WBCs over 20000/cmm As in acute infection as tonsilittis Leucopenia : decrease WBCs count as in radiation or drugs Leukemia : malignancy of bone marrow ---increase WBCs count  Muscle: Neuromuscular junction: Neuromuscular transmission: Motor end plate:junction between motor nerve and muscle Events of neuromuscular transmission:  Events of the neuromuscular transmission: *Action potential reach end of nerve *open Ca++ channels *Ca++ enter in nerve terminal *rupture vesicles in nerve terminal *release acetylcholine *acetylcholine cross cleft & sit on receptors on muscle *open Na+ channels and Na+ enter to muscle Forming depolarization (End plate potential) (EPP) *action potential is propagated in muscle *acetyl choline is degraded by acetylcholine estrase enzyme  Miniature end plate potential: Minute depolarization-----due to spontaneous release of acetylcholine Properties of NMT: 1-unidirectional----from nerve to muscle 2-delay 0.5 msec 3-easy fatigue---due to exhaustion of acetylcholine 4-Effect of ions: Ca++ increase NMT---increase rupture vesicles Mg++ decrease NMT—block rupture vesicles  *Effect of drugs: 2-Drugs block NMT *having acetylcholine like action: Curariform drugs: (Curare) 1-metacholine Mechanism of action: 2-carbachol Compete with acetylcholine receptors on 3-nicotine small dose the muscles----prevent binding of acetylcholine to receptors----prevent depolarization *having anticholine estrase activity: 1-neostigmine 2-phsostigmine 3-DIF  Myasthenia gravis: *heriditary disease *affect female more than males *autoimmune disease *patient has antibodies against acetyl choline receptors on the muscle side considering them non self *this may lead to weak muscle contraction *in severe cases patient may die from paralysis of respiratory muscles Treatment: Anticholine estrase drug----Neostigmine----increase acetylcholine-----increase muscle contraction  NB: the same condition may occur in case of presence of curare like substance OR Secretion of small amount of acetylcholine  Electric changes following skeletal muscle stimulation: FL -40 RMP -90mv duration of A.P. 2-4 msec velocity 5m/sec  *The action potential preceds the contraction by 2 msec. NB: there is absolute &relative refractory periods in the muscle similar to nerve  Molecular mechanism of muscle contraction: -the action potential cross the NMJ to muscle -it pass on surface of muscle -it enter inside muscle by T tubules -stimulate DHP receptors on the T tubules -stimulate ryanodine receptors -release Ca++ into cytoplasm -Ca++ bind to troponin--- form complex -complex remove tropomyosin from active site of actin -head of myosin bind to active site of actin generate tension bending of arm need energy from ATP release then attach again Cross of Actin over Myosin  Relaxation: -Ca++ is removed from cytoplasm actively ---to the sarcoplasmic reticulum. -break complex -tropomyosin return to cover active site of actin -relaxation All Or Non law: Def: the muscle either contract maximally OR does not contract at all *the nerve, muscle, cardiac muscle, visceral muscle obey all or non law  Types of skeletal muscle contraction: Isotonic contraction: muscle shorten----tension remain constant Isometric contraction: tension increase while length of muscle remain constant  Isometric isotonic length constant Decrease Tension increase Constant work No work done Work is done Effeciency Zero 25% Energy Less energy consumption More energy Time Less time Long duration Example Muscle contract to move Contract muscle---lift object— weight which is too heavy to body moves be removed or (push the wall)  Most muscles contract as a mixture of isometric & isotonic contractios Muscles start contraction isometric & completed isotonic Factors affect muscle contraction: 1-muscle fiber 2-stimulus 3-length tension relation ship 4-load velocity relation 5-muscle fatigue  1- muscle fiber: Each muscle is formed of slow fibers & fast fibers Slow fibers Fast fibers Small muscle fibers----supplied by slow Large fibers---supplied by rapid conducting conducting fibers fibers Contain many OXIDATIVE enzymes Contain many GLYCOLYTIC enzymes Have low ATPase activity Have high ATPase activity Red due to ---contain myoglobin Pale due to---less blood supply has high blood supply less myoglobin Highly resist fatigue Less resistance to fatigue Contract slowly & relax slowly Contract rapid & relax rapid Adapted for long posture maintaining Adapted for skilled movement  2-stimulus factors: Strength of stimulus: *increase strength of stimulus Increase active muscle fibers Increase force of contraction Frequency of stimulation of muscle: Increase frequency of muscle stimulation Increase Ca++ released from Sarcoplasmic reticulum Increase force of contraction Low frequency of stimulation Moderate frequency of High frequency of stimulation stimulation *Separate twitches *clonus *tetanus *enough time for relaxation *contraction with incomplete *contraction with no relaxation relaxation *no time for relaxation  3-length tension relation ship: Starling law: Def: the more the initial length of the muscle (preload) the more the force of contraction (tension) within limits. maximal force (optimal over lap Actin& myosin tension 2.2micron length of sarcomere  decrease force(decrease Tension overlap actin & myosin) cross bridges with no actin >2.2 micron length of sarcomere  decrease force (over lap two Tension ends of actin & myosin) < 2.2 length of sarcomere  4-load velocity relation: The weight which the muscle contract to lift is the after load Increase after load----increase duration of contraction decrease velocity of shortening decrease amount of shortening  5- muscle fatigue: Repeated strong stimulation of muscle Lead to muscle fatigue *decrease strength of contraction *incomplete relaxation causes of fatigue: 1-accumulate metabolites (lactic acid) 2-deplete ATP,creatine,glycogen 3-deplete acetylcholine  Energy sources & muscle contraction: Energy is consumed by the muscle during rest and during muscle contraction Energy during rest Energy during muscle contraction *to maintain RMP Energy consumption increase *formation of chemical substances *formation of muscle tone The ATP is the immediate source for energy for contraction ATP in muscle not enough except for 5-6 seconds The ATP is reformed continuously by 1-phosphocreatine (phosphagen system) 2-anerobic system (glycogen lactic acid ) 3-aerobic system(oxidation of food to provide energy) Phosphagen system Anerobic system Aerobic system *for normal power surges *for extra power *for prolonged activity *Ex: intermediate race 200- 800 meter run 10-15 seconds 30-40 seconds Un limited time  Oxygen debt: Def: it is the O2 consumed post exercise above the pre exercise level OR the basal O2 consumption level. Causes of O2 debt: -remove excess lactic acid formed during exercise -replenish ATP , & creatine phosphate -replace O2 from myoglobin -  Rigor mortis: Def: rigidity of muscle several hours after death Cause of rigor mortis: -loss of ATP needed for relaxation -destruction of muscle protein 15-25 hours later Importance of rigor mortis: Medicolegal -----determine time & shape of body at death  Smooth muscle: Characters of smooth muscles: -involuntary -innervated by ANS -not divided into sarcomeres -no troponin -no T tubules -weak sarcoplasmic reteculum  Skeletal muscle Smooth muscle *Resting membrane potential *un stable potential = _ 50mv *Firing level = _35 mv depolarization take 15 mv *the smooth muscles have Na+ channels they leak Na+ to inside the muscle DURING REST ---form slow waves over surface of muscle When the muscle reach firing level Open Ca++ channels which is greater than Na+ channels & form depolarization The action potential is either -spike potential ----duration 50 msec -Action potential with plateau  Contractile process of smooth muscle: *The Troponin –Tropomyosin are replaced by Calmodulin in the smooth muscles *the smooth muscle has weak sarcoplasmic reticulum ----so the contraction depends on the Ca++ which enter from outside beside the Ca++ which is released from sarcoplasmic reticulum *Ca++ combine with calmodulin *Calmodulin phosphorylate myosin *phosphorylated myosin interact with actin  Characters of smooth muscle contraction: - Dual nerve supply (sympathetic & parasympathetic) - spontaneous contraction - length tension relation ship (the more the length of muscle before contraction the more the tension in muscle within limits) -ions & hormones affect contraction