Blood Physiology Lecture Notes PDF

Blood physiology Blood: —> Blood makes up approximately 8% of the body weight in an adult person —> 8% equal round about 5L of blood => an adult person has 5L of blood within the body Functions of blood: —> main function related to transport of: a. Respiratory gases like O2 and CO2 between resp...

Blood physiology Blood: —> Blood makes up approximately 8% of the body weight in an adult person —> 8% equal round about 5L of blood => an adult person has 5L of blood within the body Functions of blood: —> main function related to transport of: a. Respiratory gases like O2 and CO2 between respiratory system and tissues b. Nutrients from gastrointestinal system through whose wall they are absorbed into the blood up until the organs which use them for energy production or storgae c. waste products from tissues to excretory systems like the kidneys, the respiratory system, the gastrointestinal system or sweat glands d. takes part in endocrine regulation by transporting biologically active substances like hormones from the endocrine glands to the tissues where they signal for a certain function e. equilibrates heat into different regions of the body —> transports heat from the place it is produced at to all other tissues which distributes the heat almost fairly around the body to keep every organ warm and steady —> blood helps to maintain homeostasis, defined as: —> relatively stable internal environment => ensured through transport of different substances like heat etc from the point at which they enter the blood stream to any body part (all around the body) thus making a stable external environment for each of the cells to be in ad to exist —> blood also secures hemostasis: --> plasma proteins and blood cells interact with each other in case of blood vessel damage to form a clot which then prevents severe bleeding and therefore immense blood loss —> blood participates in defense: —> mostly immunological —> released with immune cells located within the blood such as certain plasma proteins which form antibodies => defend body against foreign, dangerous and contagious antigens which might enter the body from the external environment Blood composition: —> blood needs to be put into a centrifuge, which rotates extremely fast, to separate blood into its two main compartments —> blood contains: a. blood plasma (upper part of blood content when leaving the centrifuge) —> mostly yellowish coloured —> liquid part of body content b. blood cells (white line, middle part and bottom part of blood content after leaving the centrifuge) —> erythrocytes (make up the biggest part of blood cells) => 99% of all cells in the blood are erythrocytes —> leucocytes (small amount) —> platelets (small amount) Hematocrit index: —> shows percentage of whole blood volume which is occupied by erythrocytes ≈> amount of blood cells is defined as hematocrits index —> differs for males and females: a. males: 40-50% b. females: 35-45% => mainly depends on erythrocyte amount since they make up the greatest part of the blood cells Functions of blood cells: a. Erythrocytes: —> make up the greatest part of the blood cells —> Function: => general function related to transport of haemoglobin —> Amount/ Number: => differs for males and females a. males: 4.5-5.5x10^6 mm^-3 (4.5-5.5 millions of cells per micrometer of blood or also known as cubic millimetres ) b. females: 4.0-5.0x10^6 mm^-3 —> Origin: => red bone marrow —> Live: => 120 days —> 120 days until the majority of them is removed from circulation —> they are transferred to the spleen of capillaries which are quite narrow for all the erythrocytes to pass through without the rupture or break down of their membrane —> erythrocyte development: erythopoesis Erythropoiesis: —> development of erythrocytes —> takes place in red bone marrow —> has one single stimulating regulatory factor known as: erythropoetin —> besides erythropoetin the erythrocyte development depends on other factors as well: a. DNA synthesis and multiplication of erythrocytes, which urgently requires vitamin B12 and Folic acid Vitamin Ba ) => a deficiency of those two majorly important substances in food leads to a large erythrocyte development which are really rich in haemoglobin (impaired absorption in alcoholics causing the important dinitrosalicylic acid not to be able to be produced to be part of the genetic material needed for the make up of new erythrocytes —> causing a macrocytic anemia as the little amount of erythrocytes which is still present needs to compensate the lacking erythrocytes which makes them grow in their size ) b. Hemoglobin synthesis: —> hemoglobin is main part of erythrocytes and the actually part the oxygen binds to —> primarily needs iron since that it the molecule the oxygen binds to within the hemoglobin => in case of an iron deficiency the erythrocytes become small and are quite poor in the amount of haemoglobin which they carry (microcytic anemia) —> besides iron, hemoglobin consists of proteins a. heme (porphyrines) b. globine part  Erythropoetin: —> produced primarily (up to 90%) in kidneys —> small amount of it is produced in the liver and other tissues (approximately 10%) —> production is stimulated by: Hypoxia => low partial pressure of oxygen in the blood (like in a- and dyspnoea, reduced partial pressure of oxygen in the environment) —> stimulation of the erythropoetin activity by: Sympathetic nervous system => during exercises the sympathetic nervous system such as the low partial pressure of oxygen might lead to an increased amount of erythropoetin in combination —> since erythrocyte amount in exercise creates much better conditions for the oxygen transport to peripheral tissues erythropoetin can be used as doping in sports to secure a great oxygen supply and better working capacity of muscles by the artificial increase of the erythrocyte amount in the blood General metabolism of the B12 vitamin (Cobalamine): 1. incorporated to the body by the diet, mostly of animal products as it is bond to proteins 2. by the help of an acidic medium and the protein break-down enzyme pepsine, the vitamin B12 is separated from the dietary proteins ↳ gastric juice 3. As the vitamin B12 is released it bind to Haptocorrin (transport portein) —> Haptocorrin (HC), also commonly known as the R-protein, or the R-factor, or previously referred to as transcobalamin I (TC-1), is a unique glycoprotein —> produced and secreted by the salivary or gastric glands of the oral cavity, in response to ingestion of food => The essential function of haptocorrin is protection of the acid-sensitive vitamin B12 while it moves through the stomach 4. Transportprotein, Haptocorrin, transports vitamin B12 into the duodenum 5. Transport protein is degraded in duodenum 6. Vitamin B12 is released 7. Free vitamin B12 binds to intrinsic factor which is secreted by the gastric parietal cells 8. Intrinsic factor and the vitamin B12 complex is transported to the end of the small intestine 9. Once the ileum is reached, the intrinsic factor bind to the epithelial receptor 10. Receptor binding initiates the vitamin B12 complex, that is coupled to the intrinsic factor, to be up-taken by the endosomes ( EndOclftosis ) 11. Endosomes, vesicles, recycle the cell surface receptors or degrades them 12. Vitamin B12, together with a second transport protein known as transcobalamine, is transported into the interstitial space and the blood 13. From the blood the vitamin B12 is transported to the liver 14. The liver finally stores vitamin B12 and is able to release it in small quantities in case it is needed for the erythrocyte development Storage capacity of vitamin B12 in the liver: —> thousand times greater concentration than it is actually needed for the everyday erythrocyte development => if something goes wrong in the vitamin B12 metabolism or transport it will eventually lead to macrocytic anaemia (after approximately 3 years as that is when the storage is depleted) —> most issues in the vitamin B12 metabolism and supply are related to a shortness of food, vegan life-style, gastric diseases in which parietal cells can no longer secrete intrinsic factors (vitamin B12 cannot properly be transported to the epithelial cells)  => person might develop anaemia, with large erythrocytes that are rich in hemoglobin !! Vitamin B12 is working as a co-factor in the folate metabolism and the homocysteine metabolism which are both needed for the multiplication of erythrocytes Iron metabolism: —> Iron is required for erythrocyte or more precise hemoglobin synthesis —> also used for enzyme synthesis (several different tissues) —> can be stored (in liver) 1. Received/ Up-taken via the diet/ food —> mostly found in animal products but also some kinds of plants contain iron —> plant iron is absorped far less intensively than animal or heme iron 12 - Finger - 2. On the duodenums apical surface the iron, in its ferric form Fe (III) is reduced to ferrozine Fe (II) Darm 3. Ferrozines are transported via the divalent transporters (DMT) into the epithelial cells 4. From epithelial cells the ferrozine is transported out through the ferro poritins/ iron transporter into the blood 5. Within the blood the ferrozine is converted back into ferric iron Fe (III) 6. In the blood stream ferric ion is bond to the transport protein known as transferrin (Tf-Fe2) 7a. Via the blood, the iron that is coupled up with the transferrin, is transported to any place where it is needed (several different tissues) but in regard to the hemoglobin synthesis it is delivered to the: => to the red bone marrow 7b. for any other case like enzyme synthesis it is transoprted to various tissues 7c. for storage purpose it is transoprted to the liver 8. If erythrocytes are synthetized and later on about to end their life as they are finally digested by splenic macrophages, their iron content can be recycled by getting back to the transferrin in the ciculation Iron overload in hepatocytes: —> more iron is taken up than actually used in the body —> hepatocytes are able to secrete a hormone called Hepcidine => Hepcidine is able to block the ferron poritins/ ferronize transporters —> dietary iron is no longer absorbed into the blood stream !! Hormone Hepcidin is used to regulate the blood iron levels Iron metabolism within the cell: —> Transferrin, which is transported to the tissues, binds to a specific receptor —> receptor binding initiates uptake not just of Tranferrin but also of receptor into an endosome —> receptor and Apotranferrin are recycled, the receptor is moved back to the cell surface while the transferrin, without an iron, is moved back into the circulation so the iron is stored in the cell in Ferritin form when it is not recently used for the heme synthesis —> Heme is incorporated into erythrocyte Protein content of heme- focused - globin part: —> hemoglobin structure contains protein part known as globin part —> Globin part changes during the life-time of the individual a. in embryonic life: —> epsilon (ε) and zeta (ζ) hemoglobin chains b. in feti: —> hemoglobin F is pre-dominating which consists of 2 alpha (α) and 2 gamma (γ) chains => gamma (γ) chain synthesis is suppressed after birth while beta (β) chain synthesis is activated c. adult hemoglobin: —> mostly consists of two (2) alpha (α) and two (2) beta (β) chains that together form hemoglobin A —> a small amount consists of hemoglobin A2, which consists of two (2) alpha (α) and two (2) delta (δ) chains —> another very small amount is haemoglobin F, which is made of two alpha (α) and two gamma (γ) chains Hemoglobin content: —> differs for males and females a. males 14-18g/dl b. females 12-16g/dl —> besides of these general numbers each single cell is further characterised by three parameters: a. mean corpuscular hemoglobin (MCH): I. Physiological condition: 26-34pg (picograms) II. Iron deficiency anemia: reduced hemoglobin amount III. Vitamin B12 deficiency: increased hemoglobin amount => amount of hemoglobin in each single erythrocyte b. mean corpuscular hemoglobin concentration (MCHC): I. Physiological condition: 31-38% => for each single erythrocyte c. mean corpuscular volume: I. Physiological condition: 82-98 fl (femtoliter (1 fl = 10-15 Liter)) II. Vitamin B12 deficiency: increased III. Iron deficiency: decreased  Hemoglobin in blood is present in two different forms in physiological conditions: a. Oxyhemoglobin - hemoglobin transports oxygen b. Carbaminohemoglobin - helps in transport of carbon dioxide (CO2) Hemoglobins pathological forms a. Methemoglobin - pathological form (unable to transport O2) —> ferrozine is substituted by ferric ion, which cannot transport oxygen sickggm.io ? —> in very minor concentrations in the blood —> in case of poising or drug use the amount of methemoglobin will increase tremendously ← => especially in those whose oxidative stress is more expressed on erythrocytes like in glucose-6-phosphate dehydrogenase deficiency b. Even other diseases leads to the pathological globin formation —> instead of alpha and beta chains the hemoglobin might contain different chains Main function of hemoglobin: —> Transport of respiratory gases (O2) —> Buffer function, especially in erythrocytes as they bind hydrogen ions which are produced by carbon dioxide transport form generation Hemolysis: —> rupture of erythrocyte membrane releasing free hemoglobin into the blood stream —> physiological condition: => occurs physiological after approximately 120 days, when all the erythrocytes are removed mostly by spleen macrophages => their structural proteins and iron is recycled —> pathological condition: => Erythrocytes do not live the full 120 days and die off before that Pathological hemolysis triggered by: —> erythrocyte defects: a. hemoglobin defects (pathological) => if abnormal hemoglobin is formed like in sickle cell anemia (hemoglobin molecules polymerize intracellularly and lead to a cascade of events resulting in decreased deformability and increased adhesion of red blood cells (RBCs)) b. enzyme deficiencies => like glucose-6-phosphate dehydrogenase c. membrane defects => erythrocytes are deviated from normal disk form causing them to become spherical leading to a decreased flexibility and correspondingly their rupture in the small capillaries —> external factors: a. mechanical damage - => if blood is subjected via mechanical vibrations causing the erythrocytes to rupture  b. osmotic hemolysis => if erythrocytes are exposed to a hypotonic they rupture => if they are put into a hypertonic solution they tend to shrink instead of rupture, even though ruptures can still occur c. thermal hemolysis - increase or decrease in temperature as: => an increased temperature denaturates proteins of the erythrocyte membrane making it fragile while => decreased temperature cold could cause crystals of proteins within the erythrocytes which eventually causes the rupture of the cell membrane d. toxic damage of erythrocyte membrane => mostly through substances that dissolve through phospholipid layer like alcohol e. drug induced hemolysis => membrane gets more fragile f. infections => streptococci inefctions => malaria infections g. autoimmune triggered hemolysis => triggered by antibody and antigen reaction like in wrong blood group transfusions h. radiation Consequences of hemolysis: a. hypoxia => due to the loss of haemoglobin —> as it is no longer in the erythrocytes it loses its ability to carry oxygen —> Problem: hemoglobin should usually be in erythrocytes to prevent its removal from circulation to the capillary wall or the kidneys => in case erythrocytes rupture and hemoglobin is freed up it is removed from the circulation through the oxygen carry capacity of blood decreases b. obstruction of blood vessels in microcirculation —> occurs if ruptured erythrocytes are not removed fast enough  c. removal of nitric oxide - vasoconstriction —> hemoglobin which is getting free and into the circulation attracts the nitric oxide, which is an endothelial derived potent vasodilator degraded by the hemoglobin in blood plasma it leads to vaso- constriction so deficient microcirculation => increase of blood pressure d. Kidney failure —> hemoglobin is filtrated through the kidneys as it is now small enough to pass the glomerular filtration membrane => becomes rather big to move through the nephron tubules where water is getting absorbed back into the blood stream —> hemoglobin which is filtrated in high amounts can obstruct nephron tubules leading to inhibition of further filtration so kidney failure e. increased potassium (K+) concentration in extracellular fluid (potassium concentration inside the cell is greater than in the outside) —> if erythrocytes rupture the potassium concentration outside the cell rises just as when they undergo… —> Erythrocyte hemolysis which leads to the increased potassium as lots of potassium, which inside of the erythrocytes, is getting freed up into the circulation —> potassium concentration increase might lead to the depression of the excitable tissues => heart muscle is not able to generate impulses and contract => nerve cells are not able to generate impulses and conduct them along nerve fibers => suppression of excitable tissue function b. Leukocytes —> 4000-8000 cells/mm^3 of blood —> Leukocytes are produced by the bone marrow —> divided into different sub-groups: I. Neutrophils: —> amount: 50-70% of all Leukocytes => biggest portion —> main function: phagocytosis een eating => able to phagocytose in blood stream and, according to the bodies need, they can cross the capillary wall and enter the tissue where it causes phagocytosis as well in inflammatory areas —> They can phagocytose all cells and cell parts and also microorganisms —> subdivided according to their maturity level a. segmented neutrophils —> rather older neutrophils —> make majority of neutrophils in circulation b. bent forms —> rather new neutrophils —> make minor portion —> in case of infection: => bent forms are getting released more from the bone marrow causing their number to increase in the circulation designating inflammatory process in the body due to… —> rather slow neutrophil development in relation to their need/ use in the circulation or in tissues during an inflammatory process II. Eosinophils: —> make up 2-4% of total leukocyte number —> Eosinophils also make weak phagocytosis —> main functions are related with the: a. defense against the allergic inflammation and b. defense against the parasitic infections III. Basophils: —> approx. 0-1% in circulation => 0% doesn’t mean that the person doesn’t have any cell but… —> just from the randomly counted 100 cells there can be no or just one single basophil leukocyte as they are that rare —> can also cause weak phagocytosis —> contain granules which store: a. heparin => inhibiting blood clotting b. histamine => stimulating inflammatory reactions and pain in the tissues => mostly connected with allergic inflammation is tissues c. bradykinin => helps in inflammatory processes IV. Monocytes: —> belong to the agranulocytes ( no gran u / es ) —> make up 2-10% of all the leukocytes —> main function: phagocytosis in tissues => in case of inflammation they are going through the capillary wall and turn into macrophages —> macrophages are able to digest the damaged cells and also microorganisms V. Lymphocytes: tound in 14MDM nodes which —> Make up 20-40% of all the leukocyte amount integrale them into lymph cousin g lymph to have —> related to the immune reactions an immune function as —> divided into 2 general groups well a. T-Lymphocytes or T-plasm cells —> related to the cellular immunity b. B lymphocytes or B-plasm cells —> related to the humoral immunity meaning the antibody production ↳ immun ity againts extraCellular / foreign Substances c. Platelets —> Third part of the cells is made of platelets —> no actual cells but rather parts of the megakaryocytes cytoplasm —> megakaryocytes are generated in the red bone marrow => responsible for making platelets, which are necessary for blood clotting —> live approx. 8-12 days —> mostly needed when blood vessel is damaged —> approx. 150.000-300.000 mm^3 of blood —> Main function: hemostasis a. cell membrane of platelets —> inhibits adhesion/ attchment to normal endothelium —> stimulates attachment of them to the damaged sides b. store granules I. Thromboxane A2 and Serotonin => trigger blood vessel constriction in the side of damage —> released of thromboxane A2 and serotonin upon the need of the body II. Thromboxane A2 and ADP (adenine diphosphate) —> activates other platelets and stimulate their adhesion and aggregation => Activated platelets express receptors for fibrinogen —> able to concentrate fibrinogen in the clot formation side III. Calcium —> released for effective hemostasis IV. Fibrin —> stabilizing factor => stabilizes fibrin tract after the formation V. Growth factors for endothelium VI. Fibroblasts in smooth muscles —> stimulate growth of blood vessel wall after the damage => renewal of blood vessel and also circulation d. Blood plasma —> Last part of blood —> not occupied by blood cells —> Makes up approx. 5% of the body weight = 3 (three) litres of blood plasma for adult person —> Composition is mostly made of water ≈ 90% —> next biggest portion is made of proteins ≈ 6-8% (6.5-8.5 g/dl) —> approximately 1% of blood plasma contains inorganic substances: a. sodium b. potassium c. calcium d. chloride e. bicarbonate ions => flowing with the blood stream —> contains and transports different nutrients like a. glucose b. amino acids c. different lipoproteins (lipids) } } main nutrients —> waste products like a. creatinine from the muscle creatine → protein metabolisch b. bilirubin from the heme breakdown c. urea from protein breakdown —> contains dissolved gases a. O2 and b. CO2 => rather in low concentration —> not very well soluble in the water environment —> contains: a. different hormones, b. vitamins, c. biologically active substances and d. different ingested substances from the gastrointestinal strand e. Plasma proteins —> make 6,5-8,5 g/dL —> further subdivided into several types according to the electrophoresis a. albumins —> majority of plasma proteins —> make approx. 60-70% of total plasma protein amount —> produced in liver b. globulins —> divided into 4 fractions according to the electrophoretic properties I. Alpha1 approx. 3%, II. Alpha2 approx. 8% III. Beta globulins approx. 10% and IV. Gamma globulins 12% (antibodies) c. Fibrinogen —> makes 2-4 g/dL —> All these proteins, except gamma globulins, are produced in the liver => Gamma globulins are antibodies/ Immunoglobulins —> produced by the B cells (specialised white blood cells) Function of plasma proteins: a. albumin is mostly related to: —> determination of colloid-osmotic pressure A- =T Dressuren = Es filtration => keeps water in the circulation ↑ BP = Es = ¥ presste b. Buffer function ☆ filtration Es BP = = —> plasma proteins can accept free hydrogen ions => help to maintain normal plasma pH c. Bind and transport various substances like I. hormones e.g. thyroid hormones II. ions - iron is transported by the transferrin III. cholesterol IV. bilirubin V. different drugs => binding causes substances to remain longer in circulation d. take part in the coagulation —> work as coagulation factors —> fibrinogen is converted into fibrin to make a blood clot e. provide immune function as antibodies —> gamma globulins f. in extreme cases: —> plasma proteins can be used as an energy source in extreme severe circumstances due to the long fasting  Blood groups and grouping —> on the surface of erythrocytes there are more than 30 different antigens => determine blood group —> 2 most important and most antigenic blood group systems a. AB0 system b. rhesus system a. Blood groups in AB0 system: —> 4 blood groups in AB0 system —> named according to their aglutinogen/ antigen on the erythrocyte membrane => antigen is genetically determined —> Besides of these aglutinogens one has different aglutinins in the blood plasma which => do not correspond to aglutinogen which is on the erythrocyte 1. 0 blood group —> doesn’t have any of A and B agglutinogens on erythrocytes —> blood plasma has both anti A and anti B aglutinins => approx. 47% of the total population 2. A blood group —> A agglutinogen on the erythrocyte while —> Anti B agglutinin is in blood plasma —> second most common blood group ≈ 41% of the population 3. B blood group —> B agglutinogen on the erythrocyte —> Anti A agglutinins in blood plasma —> quite rare blood group ≈ 9% of population 4. AB blood groups —> both agglutinogens A and B on the surface of erythrocyte —> neither of anti A and anti B aglutinins in the plasma —> least common blood group in the population ≈ 3% only of people Determination of blood group in ABO system: —> use of 2 (two) standard serums with antibodies: a. anti-A and b. anti-B Blutgruppe Blutgruppe A 1. 10 times smaller blood drop into each standard serum B 2. mix the combination properly ↳ Antigen 4) Antigen 3. result visible with certainty after 3 minutes but tendency observed right away aglutinin a. anti A serum seeks for A aglutinogen on erythrocyte surface —> If it is present: anti A binds with A aglutinogen and causes agglutination b. anti B serum seeks for B agglutinogen on erythrocyte surface —> if it is present: anti B binds with the B agglutinogen and blood agglutinates I. no agglutination with anti A and B standard serum: —> indicates that no A and B aglutinogen is present on the surface of erythrocytes => corresponds to 0 blood group  II. If agglutination takes place in anti A standard serum but not in anti B => having A blood group III. If agglutination is taking place in anti B but not being present in anti A => having B blood type III. if aglutination takes place in both standard serums => indicates presence of both blood groups and agglutinogens => known as AB blood group type —> Blood group should be known before the blood transfusion Blood transfusions: —> made only in between persons of corresponding blood group types —> Sometimes in AB0 system cross transfusion is allowed Cross-transfusions: —> only allowed for a small amount of blood —> In this case 0 group blood can be given to all other blood group type persons => universal donor 10 ) - —> AB blood group person => can receive blood from all other three blood group type persons —> universal recipient —> allowed only in small volumes => In case of transfusion of 0 blood group into the AB person —> no aglutinogens takes place —> small amount of anti A and B which is transfused together with the blood plasma is dissolved in about 3 liters of persons blood plasma => antibody concentration is not enough to destroy erythrocytes which are having A or B aglutinogens on the surface Probability: —> European countries: 0> A > B> AB —> Asian and African countries: B> A> AB> 0 b. Blood groups in rhesus system: —> 3 possible paths of agglutinogens on the surface of erythrocytes: 1. C 2. D, causing most of transfusion reactions in rhesus system 3. E —> D agglutinogen: —> causing most of transfusion reactions in rhesus system which is why… => Rhesus blood groups are determined according to the D agglutinogen presence 1. Rhesus positive (Rh+): —> D agglutinogen present —> most popular ≈ 85% of white skin coloured population ≈ 95% of black skin coloured population such as Asians => relative stable and not greatly changing according to geographical reasons —> dominant allele, causing it to be more common 2. Rhesus negative (Rh-): —> D agglutinogen not present —> less popular ≈ 5-10% => Neither case comes along with any agglutinants against D agglutinogen in the blood plasma Blood group determination in Rhesus system: —> same principle of typing than in ABC system —> only difference: using standard serum with the anti D antibodies seeking for D agglutinogen on the surface of erythrocyte => If it would be present: antibodies will bind to agglutinogen and cause erythrocyte clotting => If the D agglutinogen wouldn’t be present: no agglutination —> other serum which is used = control serum/ Negative control —> doesn’t contain any blood group antibodies => if agglutination takes place something is wrong with blood group typing (taken either clotted blood from finger or agglutination took place due to the other antibody- antigen complexes which are outside the blood group system) —> if negative control comes back positive (clotting occurred/ agglutination) a mistake was made => mistakes are mostly due to temperature; agglutination due to cold  => serum tests are kept in the fridge and if test comes back the test serum most likely was too cold —> negative D/ control serum can be artificially made in comparison to the Anti A and Anti-B —> test result takes up to 5 minutes until it is certain Rhesus positive (Rh+): —> agglutination in anti D —> no agglutination in control serum => no agglutinogen on erythrocytes => no agglutinin in plasma Rhesus negative (Rh-): —> no agglutination in either of them (standard serum + control serum) => Agglutinogen on erythrocytes => no agglutinin in plasma Blood transfusions: —> transfuse of rhesus negative blood into rhesus negative blood —> transfuse of rhesus negative blood into rhesus positive blood I no agglutinogens in Rh-0 ) => since rhesus negative people are less in the population, usually rhesus negative blood is not wasted for rhesus positives —> transfuse rhesus positive blood into rhesus positive person —> NO transfusion of rhesus positive blood into a rhesus negative person lagglutinogen Dcauses —> rhesus positive blood into rhesus negative blood antibody Production ) => antibodies against the D agglutinogen are produced —> reach the maximum concentration after 3-4 months —> form agglutination over the first 2-4 weeks after transfusion which are enough to built the base for damage when… —> transfuse rhesus positive blood into rhesus negative person a second time: antibodies destroy erythrocytes after repeated transfusion !!! Rhesus immune response or incompatibility in rhesus system can happen also in pregnancy of rhesus negative (Rh-) mother with rhesus positive (Rh+) fetus Pregnancy of rhesus negative (Rh-) mother with rhesus positive (Rh+) fetus: I. mother does not have any antigens and antibodies of rhesus system II. fetus is rhesus positive and has D antigens on the surface of its erythrocytes but no antibodies present in blood plasma —> During the first pregnancy, nothing happens with the fetus to mother because circulation from mother is separated the fetus —> During the delivery of fetus, the inner placenta develops small microscopic damages which lets fetal erythrocytes flow into the mothers circulation => Within 2-4 weeks or 3-4 months maximally the antibody production agains the D agglutinogen ( antigen ) reaches its maximum concentration => mother has finally developed antibodies against this D antigen —> injections are made from human products 1. pregnancy with rhesus positive child: —> mother after first pregnancy: blood still does not contain anti D-antigens but therefore now contains D- antibodies —> no harm for the first child as it is out of the mothers body and therefore no longer in danger/ no harm to the child (antibodies cannot be transferred by breast-mild or air) 2. pregnancy with rhesus positive child: —> anti D antibodies which were formed after first pregnancy can penetrate normal placenta wall and enter the fetal circulation => cause agglutination of fetal erythrocytes which have D antigens on the surface —> Agglutination leads to the hemolysis of erythrocytes which can lead to either a. the hemolytic disease of newborn b. death of the fetus in the uterus —> To prevent such an antibody production in the mothers organisms, all these rhesus negative mothers receive donated antibodies from blood donation which cannot cross placenta barrier and thus are unable to kill erythrocytes in the circulation => mother herself is not producing antibodies as the donated ones are strong enough —> doesn’t matter anymore which pregnancy the rhesus negative mother has --> No harm for the second fetus either —> The mother is never at risk, the harm only refers to the child as mother will not produce any extra anti- bodies which would otherwise be able to cross the barrier to the fetus  Hemostasis —> Hemostasis = blood clotting —> divided into 2 groups and 3 stages 1. Group: Primary hemostasis (including stage I and II) —> takes place as first events on injured side I. Vasoconstriction at the side of injury —> decreases blood flow through the injured blood vessel => decreases blood loss II. platelet clot/ plug formation —> done by the platelet sticking to the injured blood vessel wall and sticking to each other => make a platelet clot/ plug —> decreases blood loss out of the injured blood vessel 2. Group: Secondary hemostasis - known as coagulation hemostasis —> In blood vessels which have high blood pressure and very fast blood flow as they can wash away these platelets => decreasing ability to make a plug —> In these blood vessels secondary hemostasis is needed —> interaction of plasma proteins activating each other —> lead to the fibrin mesh formation => prevents blood cell and also blood loss through the injured side I. Vasoconstriction: —> Neural vasoconstriction: => done by sympathetic nervous system which is activated due to: a. the tissue injury b. pain c. blood loss which causes physical stress to the body —> Sympathetic nervous system doesn’t constrict blood vessel only in the injured side but all over the body => sometimes sympathetic activity leads to the increase of blood pressure in the blood vessels => increase blood flow through some regions of the body —> Local smooth muscle contraction is triggered by: a. injury of blood vessel wall => leads to the contraction of nearby smooth muscle cells —> due to the electrical synapses between smooth muscle cells => constriction exactly in the side of injury —> Humoral vasoconstriction is triggered by: a. substances released from damaged tissues and platelets => Two most important substances are : 1. Thromboxane A2 2. Serotonin => released by the platelets and cause vasoconstriction in side of injury => works exactly on the side of injury - not affecting blood flow through the other blood vessels which are not damaged  —> Decreased endothelial function => if endothelium is removed from the inner surface of the blood vessel it is not able to keep normal concentration of vasodilator substances like: a. nitric oxide b. prostacyclin and ( PGIZ POTEZ ) , c. endothelial derived hyperpolarizing factor (EDHF) —> synthesized in the endothelial cells => increases of vasoconstriction triggered by the reduction of vasodilators => works exactly on the side of injury - not affecting blood flow through the other blood vessels which are not damaged II. Platelet plug formation: —> depends on the platelet function —> Platelets at the side of injury bind to the subendothelial tissues => change their shape thus activate them —> If platelets contact with the sub-endothelial tissues they activate and stick to the subendothelial tissues by the help of two (2) receptors: I. 1a receptor —> sticks platelet directly to the sub- endothelial tissues; meaning collagen fibers II. 1b receptor —> uses von Willebrand factor —> sticks platelet even more tightly to the sub-endothelial tissue —> Further receptors are involved in the plaque formation: III. 2b/3a receptor —> expressed only on the activated platelets —> binds fibrinogen => platelets concentrate fibrinogen in the sides of blood formation —> later it will be converted into the fibrogen  IV. Platelets are also expressed other receptors like receptors for: a. Thrombin (which will appear later) b. ADP (adenosine diphosphate) c. Thromboxane A V. alpha 2 receptors —> cell surface receptors => meant to bind epinephrine I additional vasoconstriction ) —> Platelets sticking to the sub-endothelial tissues also changes their secretory abilities => granules which are inside the platelets are released out => signal the other platelets about the injury of the blood vessel —> When the blood vessel also is injured or endothelium is removed: => platelets which are coming by this injury side stick to the sub-endothelial tissues => start to secreting substances —> two most important substances: a. Thromboxane A2 b. ADP => make these circulatory platelets sticky allowing them to stick to the other platelets —> formation of platelet plug —> At the same time endothelial tissues which are still on the surface of the blood vessel secrete substances like: a. PGI2 (Prostaglandin I2) (prostacyclin) b. nitric oxide => decrease stickiness of the platelets which escape the clot formation side —> In case if platelets escape this side and come into the place where normal blood vessel wall is present, prostacyclin and nitric oxide doesn’t let these platelets stick to the endothelium anymore => allow further flow of platelets with usual blood flow => prevents primary clot formation all over the cardiovascular system blood vessel  Substances and need to inhibit platelet activation: —> inhibition of platelet activation to prevent them stick to rough endothelial wall like in the cases of arteriosclerosis => inhibition of interaction between Thromboxane A2 and ADP with the platelets by: a. Aspirin (most commonly used to calm down platelets) E —> blocks synthesis of thromboxane A2 Ivasoconstrictor ) × => inhibits cyclic oxygenase pathway inhibitor —> thromboxane A2 is produced less ☐ OH & => not able to activate platelets as strong Dain b. Ticlopidine/ Clopidogrel (in case aspirin can not be used like in gastric ulcers and inflammation of gastric lining) - (Aspirin increases acidity and decreases protection of gastric mucous membrane) => blocks ADP (adenosine diphosphate) receptor on the platelets => no rapid activation ADP => no clot formation in the places where its not necessary nervus Vasari lotion trigeminus → migraene Primary Hemostasis Testing aspirin pain vasoconstrich.cn & Pair release as Different types of tests that can be used to evaluate primary hemostasis: COX 182 Inhibitor 1. Bleeding time/ Duke’s method: =D reauced DIOOD —> According to Duke the bleeding stops after 1-5 min Gotti zog a. small prick/ cut in the fingertip or more often in the ear lobe b. every 30 seconds wound has to be touched with the filter paper to check whether bleeding has stopped or not c. time from the prick of the ear lobe until bleeding has completely stopped 2. Standardised/ Ivy’s method: —> According to Ivy the bleeding stops after 1-9 min => bleeding time depends on the circulation in the skin such as the blood pressure in the circulation a. Cuff is wrapped around the upper arm b. inflated until 40 mmHg c. small scratches are made in the middle side of the lower arm d. similar method with the filter paper e. time until the bleeding stops is taken —> bleeding time can extend from 1-9 min. => tests are very dependent on: a. the skills of the doctor b. blood flow in the skin c. temperature of body and outer environment => tests are not considered as very precise => tests are replaced by platelet function analysis 3. Platelet function analysis —> more precise and most commonly used a. venous blood is taken b. blood is put into thin glass tube covered by collagen and ADP or collagen and epinephrine c. time needed by the blood to form a platelet clot is taken —> time at which the blood stops bleeding from the thin glass tube I. For collagen and epinephrine: should be below ( Coagulation is organized into 3 separate stages 1. Formation of prothrombin activator complex 2. Prothrombin activator complex converts plasma protein prothrombin into thrombin 3. Thrombin converts plasma protein fibrinogen into the fibrin —> fibrin threads make the fibrin mesh work in which blood cells (erythrocytes) are trapped => form the secondary/ red clot —> since 99% of all blood cells are erythrocytes (also within this clot) the clot appears red —> Difference to primary clotting that was formed within the primary hemostasis: --> primary clot is made up only of platelets and therefore known as white clot --> secondary clot also contains erythrocytes causing a reddish appearance 1. Formation of prothrombin activator complex: —> realized through 2 pathways: I. Extrinsic pathway —> begins in damaged tissues and proceeds in blood —> extrinsic as it begins outside the blood or determined by the substances secreted from outside the blood vessel —> activates within several seconds II. Intrinsic pathway —> begins and proceeds in blood converting inactive factors into their activated form —> activates slower —> Both of them lead to prothrombin activated complex formation 2. The coagulation cascade: —> In all the stages of coagulation cascade different but certain coagulation factors participate —> Coagulation factors are numbered from 1 to 13 under these are particular names: —> First coagulation factors are usually called by their names —> later factors called by factor number —> some factors have several names —> no sixth factor because after the discovery it was found that sixth factor is actually the activated 5th factor => excluded from the coagulation factor list Coagulation factor list: I. Fibrinogen II. Prothrombin → Converter into Thrombin III. Tissue thromboplastin IV. Calcium → needed for activities of Many factors V. Proaccelerin VII. Proconvertin VIII. Antihemophilic factor A IX. Antihemophilic factor B or Christmas factor X. Stuart-Prower factor XI. Plasma thromboplastin antecedent XII. Hagemann factor XIII. Fibrin-stabilizing factor (a added to any number indicates activated coagulation factor) —> Coagulation cascade: 1. begins with first stage known as prothrombin activator complex formation —> either intrinsic or extrinsic pathway a. the extrinsic pathway: I. tissue damage leads to the tissue thromboplastin release =>II tissue thromboplastin is mostly made of tissue phospholipids and proteins located in the damaged tissues II. tissue thromboplastin in the clot converts seventh (7th) factor into its active form III. if calcium is present the activated seventh (7th) factor converts the tenth (10th) factor (I I ) into its active state b. the intrinsic pathway: --> cascade begins with the damaged endothelium or foreign surface (like a test tube, floor or table wherever the lost blood falls on to) I. damaged tissue/ foreign surface leads to the activation of the 12th factor (XII) => 12th factor is also activated by the kinin system positive feedback II. 12th factor (XII) activates a11th factor (XI) III. activated 11th factor (XI) converts 9th factor (IX) into the active form IV. Activated 9th factor (IX) together with 8th (VIII) and calcium ions also converts 10th factor (X) into the active form => end of first stage —> later 10th factor (X) together with the 5th factor(V), calcium, and platelets factor 3 (PF3)/ platelet phospholipid forms prothrombin activated complex —> In the first part from prothrombin activated complex there is no 5th (V) factor => after thrombin activation, the 5th factor gets activated which might accelerate clotting 2. stage: —> newly made prothrombin activator complex activates prothrombin into thrombin 3. stage: I. thrombin, in the presence of calcium ions (Ca2+) converts plasma protein fibrinogen into the fibrin => At the beginning fibrin is made in the making the loose mesh —> fibrin threads are connected by a rather non-covalent bonds (easy detachment) II. In the presence of activated 13th factor fibrin is stabilized => fibrin stabilizing factor —> makes stable mesh with strong bonds in between fibrin treads III. Fibrin mesh rogue trapps erythrocytes (red blood cells) causing the formation of red clot —> clots damaged side Positive feedback mechanism in the coagulation cascade: —> Thrombin triggers fibrin mesh formation —> Thrombin also exerts positive feedback in the coagulation cascade on the factors that enforce the coagulation cascade => Factors 13th (XIII), 5th (V) and also 8th (VIII) factor, which were not directly activated by previous factors, are activated by the thrombin (Ice ) —> first thrombin molecule which is produced is not able to activate them on itself causing prothrombin conversion to thrombin to be rather slow => When first thrombin molecule is made it leads to the following effects: Positive feedback effects a. exerts positive feedback activation on the formation of next thrombin => accelerating it by 5th and 8th factor activation => increased thrombin production which supports further positive feedback reactions b. Thrombin binds with the platelet receptors => activating platelet aggregation => makes it irreversible (platelets cannot detach from each other anymore c. Thrombin also activates the VII factor, accelerating clot formation  Evaluation of secondary hemostasis —> need of venous blood 1. blood is drawn 2. Blood is put into test tube with added sodium citrate 3. Sodium citrate (na citrate) binds calcium ions (Ca2+) in blood plasma 4. Coagulation stops calcium is no longer available to support coagulation —> since almost in every step of coagulation cascade calcium ions are needed cascade 5. blood is put into centrifuge to separate blood cells from blood plasma —> blood plasma with sodium citrate = citrated blood plasma 6. clotting factors and calcium ions which can bind to citrate, are added to citrated blood plasma 7. time needed for blood plasma to make a fibrin clot is measured —> The 2 most important tests used for secondary hemostasis are: a. prothrombin time and b. activated partial thromboplastin time Explanation of tests for secondary hemostasis: 1. Test: Prothrombin time 1. citrated blood plasma is added by tissue thromboplastin, phospholipids and calcium ions 2. check how much time is needed for blood plasma to clot !!! since it includes tissue thromboplastin (which is working in extrinsic pathway) it is used for the evaluation of extrinsic and also common pathway (2nd and 3rd stage) —> test should lead to the clot formation within 12-15 seconds (physiological condition) —> To standardize the prothrombin time, the international normalized ratio is used, where prothrombin time of the subject is expressed against the prothrombin of the normal blood plasma => International normalized ratio normally should be of 70-100% Oral anticoagulants: —> act indirectly —> prothrombin time will prolong 2. Test: Activated partial Thromboplastin time 1. In this test to the citrated blood plasma surface, a surface active substance (foreign surface) is added just as, phospholipids and Ca2+ ions 2. Time taken for clot to form in blood plasma is measured !!! Since in this test the foreign surface substance triggers clot formation it is used to evaluate the intrinsic and common (2nd and 3rd stage) pathway —> The clot formation normally happens in 30-35s Classical hemophilia (deficiency of factor VIII) or under the influence of direct anticoagulants (e.g. heparin) --> Time is prolonged  —> at the end of secondary hemostasis the fibrin threats coil in between platelets and trap big blood cells like erythrocytes and leucocytes in the clot => prevents cells of flowing out Mechanism of clot retraction and fibrinolysis Clot retraction: —> After clot formation the clot retraction begins within several minutes —> Clot retraction is triggered by: a. the actin and myosin interaction within platelets => leads to their contraction —> platelets are attached to the blood vessel wall just as fibrin threats —> both of them pull the clot much closer by their contraction causing… => the closure the wound edges => blood serum being squeezed out and leaving the wound —> Blood serum is blood plasma without the clotting factors —> simply runs off the wound without clotting => yellowish liquid which appears on the surface of the wound and runs off = blood serum which is squeezed out with the help pf blood retraction —> clot retraction as ending point for clotting process itself => clot stops not only blood cells loss but also blood plasma loss through the blood vessel injury side Summary of clot retraction: —> „shrinking" of a blood clot over a number of days => edges of the blood vessel wall at the point of injury are slowly brought together again to repair the damage that occurred —> dependent on the release of multiple coagulation factors from platelets trapped in the fibrin mesh of the clot Fibrinolysis: —> takes place after hours or days —> plasmin breaks down fibrin and other coagulation factors to renew blood circulation through the blood vessel => freeing the place where new blood vessel cells can grow into —> When fibrinolysis is finished in the blood vessel, the blood flow through the blood vessel is renewed => everything is like before the clot formation Plasmin: —> Plasmin is made from the plasma protein plasminogen with the help of tissue and blood plasminogen activators —> Tissue plasminogen activators are: —> the strongest —> released from growing tissues at the side of injury Lyse ? ? —> help to dissolve the clot near the growing cells —> used in the emergence clinics to dissolve clots in unwanted places => if clot is formed in the coronary arteries leading to the coronary blood flow disruption or in brain arteries leading to the decreased CNS blood flow  —> If person is delivered to a hospital within a few hours, tissues plasminogen activator can be induced in higher concentration into the blood stream => leading to plasmin activation and clot removal —> clot is not dissolved only in the place where it wasn’t supposed to be but also in the other places in which it is urgently needed —> contraindications also for such a treatment Plasminogen activator inhibitors: —> Blood contains plasminogen activator inhibitors as well a. Plasminogen activator inhibitors sei. => inhibit plasminogen activators thus decrease plasmin formation b. Alpha-2-antiplasmin ↳ Ey degradation of dots due to ↳ => Alpha-2-antiplasmin binds to the free plasmin no fibrin distler btion => doesn’t let dissolve fibrin threats dissolve in the clot increased du ration of —> greater concentration in the normal clot b 100A Clothing => in the case of blood vessel injury this plasmin doesn’t dissolve clot immediately —> when tissue or blood activators are secreted in the higher concentration than inhibitors plasmin is activated and is able to secrete fibrinolysis !! To actually dissolve a clot for plasminogen activators need to be secreted than their inhibitors Factors that opposite blood clotting —> certain mechanisms that oppose blood clotting thus do not let clot form in all of the blood as they are stimulated 1. Endothelial factors: a. smooth surface of endothelium and also glycocalyx → redet tisslte factor ( Protein ) fand in platelets —> prevents platelets adhesion through the normal endothelium =D all 0W no proteins => repel platelets and keep them in the circulation to get dose b. prostacyclin and nitric oxide ( PGIZ Platz ) , —> decrease platelet adhesion and aggregation to the normal endothelium → vasodilalion c. tissue factor inhibitor marder to Catch Dialekt —> secreted from the normal endothelial cells and inhibits tissue factor ability to activate the 7th factor d. thrombomodulin —> endothelial surface receptor => binds to thrombin I. clot formation leads to an excessive amount of thrombin to be produced II. thrombin can escape the clot formation side III. attaches to surface receptor of the endothelial cell, known as thrombomodulin * IV. thrombin-thrombomodulin complex leads to the activation of plasma protein C anticoagu - land V. activated plasma protein C stimulates breakdown of activated factor 5 (Va) and 8 (VIIIa) VI. thrombin formation will be decreased, due to disturbed processes in coagulation cascade: a. factor 5 (V) used to accelerate thrombin formation by the protein activator complex b. factor 8 (VIII) used to accelerate the 10th back to formation with the help of 9th factor => if these 2 factors are degraded, the positive feedback on thrombin formation is eliminated => thrombin formation gets slower making it… —> unable to escape from clot formation site  reactiue * ± c- —> no clots anywhere else in the circulation can be formed Protein , => positive feedback of thrombin is inhibited c- protein aeavea from insulin 2. Thrombin inactivation: —> Most of thrombin is inactivated by absorption on the fibrin threats in the clot formation side => never escapes the clot in the general circulation —> 10-15% of thrombin is able to escape —> escaped thrombin is inactivated by the antithrombin III => plasma protein produced in the liver —> able to inactivate thrombin and other coagulation factors like 7th, 9th, 10th, 11th, 12th also kallikrein and High Molecule Work Kininogen (HMWK) in the circulation => eliminating rest of thrombin that is not absorbed by fibrin threat —> thrombomodulin helps to convert thrombin —> thrombin as an important coagulant is converted into the anticoagulant known as a protein C 3. Heparin —> itself is not anticoagulant thrombin unableto —> increases activity of antithrombin III about 1000 times provider ⑦ feedback => in presence of heparin enables antithrombin III to digest thrombin and other coagulation factors about 1000 times faster —> normally produced from the basophil leukocytes and mast cells 4. Alpha-2-macroglobulin —> works similarly to the antithrombin III —> binds only coagulation factors => doesn’t let them activate the other factors in the circulation 5. decreased temperature —> all fermentative reactions occur slower; also coagulation hemostasis is working slower => later clot formation --> that is why blood and blood components are usually kept in the lower temperatures to prevent blood clotting  Anticoagulants —> used to prevent blood clotting in the body and test tubes Used in the human body: a. direct anticoagulants —> stimulate natural anticoagulant activity —> like heparin —> injected under the skin or intra venously => can decrease coagulation but stimulates antithrombin III activity b. indirect anticoagulants —> which inhibit coagulation factor synthesis in liver —> like warfarin => coagulation factors II, VII, IX and X are vitamin K dependent factors —> warfarin inhibits vitamin K metabolism and the physiological vitamin K development => The partially carboxylated clotting factors are synthesised !! are rather inactive though —> When previously synthesised clotting factors are used up in the body, the formation of new clotting factors is not effectively => prolonged clotting Used in test tubes: a. sodium citric and b. sodium oxalate c. sodium edetate (not as common) —> anticoagulatns bind calcium ions in blood plasma => calcium ions are needed for activation of multiple coagulation factors —> coagulation factors are made up of proteins and thus they are negatively charged, just the like the proteins themselves => cannot approach each other and activate because this negative charge causes them to repel form each other —> calcium ion which is charge positively can help to keep these proteins close enough to each other to get activated —> sodium citrate and oxalate cannot be used in the body because: a. they will bind also calcium ions which are necessary for other functions (muscle contraction, activation of cardiac muscle cells generation of impulses, for nerve cells to release neurotransmitter in the synapses and so on) => if introduced to the body functions will not be realised anymore => person will be dead before coagulation will be affected  Factors stimulating blood clotting in body 1. rough surface of blood vessel —> like in case of arteriosclerosis or during the injury of blood vessel wall —> rough surface is used to stimulate clotting in the bleeding wounds => wound dressings also with the rough surfaces to stimulate clotting in the wound 2. sympathetic nervous system —> Alpha-2-receptors located on the platelets lead to aggregation —> epinephrine stimulates receptors => triggers platelet aggregation thus primary clot formation 3. increased temperature —> all the fermentative reactions, also clotting, happens faster => increases clot formation in case of injury and even without injury Some factors are needed for coagulation: —> deficiency of these factors causes coagulation to slow down 1. Coagulation factors —> needed to form the clot in the injured blood vessel 2. Vitamin K is needed —> needed for synthesis of coagulation factors —> deficiency in vitamin K causes clot formation to slow down 3. Calcium ions —> needed for coagulation in almost all stages of the coagulation cascade —> keeps these proteins close enough for activation  => condition known as anemia —> high hematocrit: —> dehydratation —> enough blood cells but not enough blood volume VB12: —> vegetarian need supplements as VB12 is not found in plants —> oral supplements might not be enough —> some injections are available for deficiencies and are absolutely necessary in case of anaemia Folic acid: —> absolutely important for women who plan to get pregnant or are pregnant —> protects and supports development of neural tube which develops brain and medulla spinals => deficiency leads too abnormalities which might me lethal —> most commonly a condition called spina bifida Iron: —> some vegetable food might contain iron but the need is so great that it is hard be covered (1kg of spinach leaves) => spinach has to be cooked for it to release the iron —> iron of raw spinach cannot be extracted —> issues with iron supplements: body can up-take only relatively small amount of iron ions which are offered to the body —> iron deficiency is the most common reason for anaemia —> even though the food might be iron rich there can still be a deficiency of the body due to the limited up- take possibility —> up-take requires acidic by-product —> iron up-take depends on iron form in food or supplements —> iron tablets might cause obstruction or diarrhoea —> great risk of allergy against iron supplements => relatively easy to get an iron deficiency but hard to get out of it —> deficiency mostly hits women due to periodical bleedings and also to the greater amount of vegetarian or vegan Hypoxia: —> either physiological or pathological —> all overweight people have a general risk for hypoxia => fat tissue consumes a lot of oxygen for oxidation and energy release —> extremely overweight people suffer from constant hypoxia even without physical effort —> risk for mountain climbers —> need to adapt to low oxygen in atmosphere —> normal people might need 24h for the adaption to high as they experience nausea, dizziness, shortness of breath etc; the body will though adapt —> in sportive competition undergoing hypoxia is a common thing to increase the amount of mitochondria and the oxygen supply => needs to be within 120 days before the competition as the erythrocytes otherwise die off —> people born and living in mountain region have a physiological increased amount of erythrocytes —> even if they migrate elsewhere the amount of erythrocytes will be kept up Intrinsic factors: —> they can get lost due to stomach removal or gastric surgery => great risk of anemia —> loss of intrinsic factors —> loss of stomach surface Sickle cell anaemia: —> erythrocytes break down any moment, way earlier than 120days, due to their sickle form that makes them less stable and more sensitive to mechanical induced hemolysis Blood grouping: —> known aglutinin; unknown antiglutinogen —> aglutinin (Anti A and Anti B) cannot be artificially made => probes come from blood donation are are taken from them for grouping Blood donation: —> 4 times a year as erythrocytes need 120days till they are recovered —> plasma donation possible every week => universal donor: blood group AB —> plasma donation: —> normal blood donation during which plasma is separated from cells —> cells are injected back into the body —> condition in which only plasma is needed: —> burned patients as they do not actively bleed but they lost and lose proteins through burned surface and liquid loss —> bleeding patients whose bleeding does not stop will receive plasma as well, besides to the erythrocytes —> patients suffering from leukaemia will receive leucocytes —> greyish mass —> also platelets can be transfused —> blood can be rejected just as an organ due to biological reactions even though grouping was a fit (happens on the level of antibodies) —> symptoms: —> shortness of breath —> fever —> loss of consciousness —> kidney failure Blood donation of O-grouped blood: —> donations, regarding the entire blood content and not separated erythrocytes, partially cause clotting/ coagulation, since O blood contains Aglutinin Anti-A and Anti B in its plasma which react with their opposite Aglutinin in the recipients blood => Aglutinin Anti-A will react with the Anti-B in the plasma of blood group A => Aglutinin Anti-B will react with the Anti-A in the plasma of blood group B —> As not the entire blood volume of Ines body is donated the coagulation is limited and not lethal —> erythrocytes will be damaged and undergo hemolysis but not at such a great rate which leads to death => donation will still be life-saving !!! Danger for second try of blood transfusion might be dangerous as antibodies are build —> When just the erythrocytes are donated no issues will occur as O group blood does not contain any antiglutinogens on their erythrocytes which might correlate with those on the A, B or AB blood type erythrocytes => aglutinogens would react with their opposite —> no aglutinins are transfused within the plasma, unlimited donation possible (hypothetically) Respiratory system Colloquium no.3