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Anästhesie (Subject) / Biochemie (Lesson)

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• Acetylcholinesterase Acetylcholinesterase (AChE) is made in and secreted by muscle cells and it lies mainly in the junctional clefts, but remains attached to the muscle by thin stalks of collagen. Once released into the synaptic cleft, most of the acetylcholine reaches the postjunctional receptors, which at the neuromuscular junction. Once released from the nicotinic receptors acetylcholine is hydrolysed by AChE, which occurs within 1 millisecond of its release.
• Ernährung und Markerproteine Retinol binding protein has a half life of 10-12 hours and may therefore reflect more acute changes in protein metabolism. It is not commonly used as a nutritional assessment parameter. Transthyretin (thyroxine binding pre-albumin) levels are less sensitive as the half life is only one to two days.  This protein is not an albumin precursor.  A value 15 mg/dl reflects early malnutrition and the need for nutritional support. Albumin levels have been frequently used.  However, it is not a very sensitive marker.  The half life of albumin is over 30 days so it takes a long time to see a change.  In addition, albumin synthesis is decreased with onset of the stress response after burns.  Acute phase protein synthesis increases and albumin decreases unrelated to nutritional status. Transferrin is a more accurate indicator of protein stores. It responds more readily than serum albumin to acute changes in protein status. Serum transferrin has a shorter half life (8-10 days) and smaller body stores than albumin. A serum transferrin level below 200 mg/dL is considered low and below 100 mg/dL is considered severe. Non-nutritional factors can also affect serum transferrin level. Fibronectin is a glycoprotein that plays a role in enhancing the phagocytosis of foreign particles. It is used a nutritional marker but levels decrease after seven days of starvation.
• Inulin polyfructose (from Jewish artichokes)   molecular weight of 5000 freely filters through the glomerular barrier  uncharged  not bound to plasma proteins freely crosses most capillaries but does not traverse the cell membrane (distribution volume is the ECF) The elimination of inulin is exponential, that is, the fraction (k) of the remaining amount in the body that disappears per unit time is constant.
• Erythrozyten Each red blood cell is about 7.5 μm in diameter and 2 μm thick. They are anucleate cells that do not contain mitochondria. In humans, they survive in the circulation for an average of 120 days. They are initially released from the bone marrow as reticulocytes, which contain residual ribosomal RNA and are still able to synthesise Hb. The membranes of erythrocytes contain a variety of blood group antigens, but not HLA class II antigens.
• Überempfindlichkeitsreaktion nach Coombs und Gell Typ 1 (Sofort-Typ): Ag-Bindung an Basophilen- und Mastezell-IgE  -> IgE-Vernetzung („bridging“) -> Degranulation mit Freisetzung von Histamin, Bradykinin, Serotonin, LT, PG, IL-4, IL-5 u.a. Mediatoren Rkt < 30 Minuten. ZB Allergische Rhinokonjunktivitis, Asthma bronchiale, Urtikaria, QUINCKE-Ödem, Anaphylaxie. Typ 2 (Zytotoxischer Typ): IgG, IgM bindet -> Komplementaktivierung, Phagozytose. Rkt in Minuten.   zB Transfusionsreaktion (ABO, RhD) Typ 3 (Immun- komplex-Typ): IgG, IgM bindet -> Immunkomplexablagerung an der Basalmembran kleiner Gefäße (Haut, Niere) -> Komplementaktivierung, Phagozytenaktivierung, Gefäß- und Gewebsschädigung Rkt innerhalb 3-8 h ZB  Vasculitis allergica Typ 4 (Zellulär vermittelter Typ, Spät-Typ) Transkutane Resorption -> Aufnahme durch Langerhans-Zellen und Transport in die regionären Lymphknoten -> Präsentation durch APZ -> T-Zell-Reaktion -> IL-1, TNF, NO, MAF, Zytokine -> Entzündungsreaktion Rkt nach 24 - 48 h zB Allergisches Kontaktekzem, Tuberkulinreaktion, Transplantatabstoßung
• Citratzyklus AS, Fett, Kohlenhydrate > Citratzyklus Acetyl-CoA > CO2, NADH/H+, FADH2, GTP oxidative Phosphorylierung in den Mitochondrien NADH/H+, FADH2 > Atmungskette > ATP Pyruvat (C3) > Acetyl Co A (C2)  Acetyl Co A (C2) + oxaloacetat (C4) > citrat (C6) Citrat > Isocitrat (C6) > alpha-ketoglutarate (C5) > succinyl-CoA (C4) > succinate > fumarate > malate > oxaloacetate. Biochemie: 200
• Anti-insulinic hormones     Growth hormone Adrenaline Glucagon Corticosteroids (not mineralocorticoids like aldosterone).  
• Peptidhormone   Typical examples of peptide hormones include hypothalamic and some pituitary hormones and are chains of amino acids which are structurally dissimilar to the cholesterol-derived steroids. Unlike the steroids, the vast majority of peptide hormones are lipophobic and interact with a cell surface receptor. These peptides have autocrine and paracrine as well as endocrine effects. Luteinising hormone-releasing hormone (LHRH) analogues are a well established treatment for prostate cancer. Peptide hormones are synthesised through deoxyribonucleic acid (DNA) techniques, for example luteinising hormone/follicle-stimulating hormone (LH/FSH), growth hormone-releasing hormone (GHRH).  
• Hypothalamus The hormones produced by the hypothalamus include: Corticotrophin-releasing hormone (CRH) Thyrotropin-releasing hormone (TRH) Growth hormone-releasing hormone (GRH) Growth hormone-inhibiting hormone (GIH or somatostatin) Lutenising hormone-releasing hormone (LHRH or gonadotropin-releasing hormone GnRH) Prolactin-inhibiting hormone (PIH) and a Prolactin-releasing hormone (PRH). Antidiuretic hormone (ADH or vasopressin) is produced in the supraoptic and paraventricular nuclei of the hypothalamus and released from the posterior pituitary.
• Entzündungsmarker Coeruloplasmin Complement (C3a and C5a) Ferritin Thrombozyten Fibrinogen    
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• Bilirubin Haemoglobin is broken down in the reticuloendothelial system, where the haem moiety (ferroprotoporphyrin) is cleaved to form biliverdin and then bilirubin, which is non-steroidal. The conjugation of bilirubin occurs in the hepatocytes and is catalysed by the enzyme glucuronyl transferase > Bilirubin wird wasserlöslich (> direktes Bilirubin, messbar im Blut, da nicht  mehr an Albumin gebunden) The process is increased by rifampicin, which is an enzyme inducer, and inhibited by valproate. Conjugated and not unconjugated bilirubin may be filtered by the glomeruli. Conjugated bilirubin is stored in the gall bladder with bile salts and acids, and the gut bacteria convert bilirubin into urobilinogen and thence urobilin  In Gilbert's syndrome the bilirubin cannot enter the hepatocyte causing unconjugated bilirubinaemia. With Crigler-Najjar syndrome the bilirubin cannot conjugate causing unconjugated bilirubinaemia. In Dubin-Johnson syndrome the conjugation is unimpaired but the bilirubin cannot leave the hepatocyte causing conjugated bilirubinaemia.  
• Hypocalciämie   total calcium < 2.10 millimoles per litre ionised calcium < 1.0 millimoles per litre. In hypoproteinaemia the total calcium is reduced but the ionised portion is normal thus clinical features are absent. causes  Hypoparathyroidism Disorders of vitamin D metabolism Sepsis Burns Rhabdomyolysis Pancreatitis. Symptome: Muscle cramps Spasm and tetany Seizures Hyperreflexia Paraesthesia Stridor A prolonged Q-T interval on the ECG.    
• Glucose Absorption Glucose absorption from the gastrointestinal tract is an active process and is dependent on sodium transporters. Glucose absorption also shares a common carrier with galactose. All carbohydrates are broken down into their constituent monosaccharides or disaccharides. Dietary starch undergoes luminal hydrolysis by pancreatic amylase prior to the release of glucose and in the case of sucrose, two glucose molecules by sucrase, which is a disaccharidase found on the brush border.
• Glukagon   Glucagon is a hormone secreted by the alpha cells of the pancreatic islets. It causes hepatic adenylate cyclase stimulation leading to the recruitment of glucose from hepatic stores (glycogenolysis and gluconeogenesis). It stimulates the secretion of growth hormone, insulin and somatostatin. It has a positive inotropic and chronotropic effect on the heart, which is unrelated to adrenergic receptors. Glucagon has a half life of less than ten minutes.  
• Isomere In cis-trans isomerism, cis refers to both substituents being on the same side of the double bond, whereas in trans there is one on either side of the bond. Diastereomers are compounds without mirror images but they do have identical molecular formulae and chemical structures. Enantiomers (optical isomers) are mirror images of each other and can rotate the plane of polarisation of polarised light around a chiral centre to the left (-, laevo, l or L) or to the right (+, dextro, d or D). The R- / S- system describes the configuration of the atoms around the chiral atom, R to the right and S to the left. The atoms of an R- enantiomer are arranged in a clockwise manner and an S- enantiomer in an anticlockwise manner (not clockwise). Tautomerism or dynamic isomerism
• Katecholamin-Synthese The precursors of adrenaline in order are: Phenylalanine Tyrosine DOPA Dopamine Noradrenaline Adrenaline. The conversion of tyrosine to DOPA is the rate limiting step, as tyrosine hydroxylase is subject to negative feedback by dopamine and noradrenalin
• Blutzuckerregulierung zu Hungerzeiten   During the first 24 hours of starvation liver and muscle glycogenolysis occur due to lower plasma insulin levels. The muscle and liver glycogen stores are exhausted by 24 hours.  This is followed by an increase in gluconeogenesis and increase in glucagon levels. Mobilisation of fat stores occurs due to increased cortisol and epinephrine concentrations. If starvation is prolonged ketone bodies replace glucose as fuel for the nervous system.  Ketone bodies are mainly synthesised in the liver. Plasma glucagon levels fall after peaking at 48 hours and reach pre-starvation levels by 10 days. The resting metabolic rate decreases by 30% after prolonged starvation.  
• Acetylcholinrezeptoren five subunits/ pentameric structure around a central ion channel subunits: 2x α, β, δ and ε (alpha, beta, delta and epsilon). In the fetus, γ (gamma) replaces ε. postjunktional auf Gipfeln der Membran. The entrance is 4 nm in diameter 
• Antikörper Fc (fragment crystalline) is formed from constant domains of heavy chains, which define isotope of antibody (for example,  IgG, IgA). The isotypes determine the properties of antibodies, for example, Activation of complement Ability to cross the placenta Half life of the immunoglobulin molecule and Binding of mast cells and basophils. FAB (fragment antigen binding) are highly variable regions, which determine the affinity/specificity of antibody for antigen.
• Plasma Cholinesterase = Pseudocholinesterase = Butyrylcholinesterase = Acylcholinacylhydrolase   Plasma cholinesterase activity may be reduced due to genetic variability. The alleles are found on chromosome 3. The alleles are usual (normal), atypical (dibucaine-resistant), silent (absent) and fluoride-resistant. About 96% of the population is homozygous for the normal gene with normal duration of action of suxamethonium. Dibucaine is a local anaesthetic agent that inhibits plasma cholinesterase. Dibucaine inhibits normal variant of the enzyme by 80% but other variant forms of plasma cholinesterases are inhibited less effectively. A patient homozygous for the fluoride-resistant genotype may still have a dibucaine number of 70 but with reduced plasma cholinesterase activity. Reduced plasma cholinesterase activity may be acquired and is associated with pregnancy, renal failure, hepatic disease, malignancy, malnutrition, hypoproteinaemia, cardiac failure, thyrotoxicosis, muscular dystrophy, burns patients and with certain drugs (Esmolol)  
• Hämatokrit Normal values are 0.4 - 0.54 (male) 0.37 - 0.47 (female). Venous blood has a higher haematocrit than arterial blood because of the entry of chloride ions into red cells (chloride shift) which is followed by water entry by osmosis. A fall in haematocrit decreases the viscosity and thus increases the flow. Therefore, a haematocrit of about 0.3 is thought to be optimal and does increase the tissue oxygen delivery. The hazards of blood transfusion and deep vein thrombosis are reduced. However, a haematocrit below 0.3 is undesirable because of reduced oxygen carrying capacity.
• Mol One mole of any gas is a gram molecular weight and at standard temperature and pressure (STP) occupies 22.4 litres, and contains Avogadro's number of molecules. Avogadro-Konstante NA: Teilchenzahl N pro Stoffmenge n. Entsprechend der Definition der atomaren Masseneinheit u beträgt die Masse m von 6,02214129 (27) · 1023 Atomen 12C im Grundzustand exakt 12 g. Auf Kohlenstoff-12 werden die molaren Massen aller anderen Elemente bezogen. At a given temperature/pressure, one mole of gas occupies the same volume as any other gas. At or above the critical temperature of a gas it cannot be liquefied by the application of pressure alone. Thus it can be liquefied by pressure when the temperature of the gas is below its critical temperature.
• Glykolyse Glucose -> Pyruvat Ort: Cytoplasma. Kein O2-Verbrauch, keine CO2-Entstehung.  Pro Mol Glucose-Abbau werden 2 ATP verbraucht und 2gebildet (Nettogewinn: 2 ATP).  Anaerob: Abbau von Pyruvat zu Lactat um NAD+ zu gewinnen und die Glukolyse fortzusetzen.   
• ANP und BNP   verstärkte Natriurese (Hemmung der tubulären Na+-Rückresorption durch Hemmung der apikalen Na+-Kanäle und der basolateralen Na+/K+-ATPase) im distalen Tubulus Erhöhung der glomerulären Filtrationsrate (Dilatation der afferenten und Konstriktion der efferenten Gefäße) Hemmung der Aldosteronfreisetzung in der Nebennierenrinde Hemmung der Renin-Sekretion allgemeine Vasodilatation (Hemmung der Endothelin-Freisetzung). antiproliferative, eine antihypertrophe und antimitogene Aktivität auf das kardiovaskuläre System  
• Rückresorption von Wasser in der Niere- wo wieviel? Most of the water of the glomerular filtrate is reabsorbed by the proximal convoluted tubule (65-70%) and is termed "obligatory" absorption. Sodium is the main osmotic driving force for the reabsorption of water and other solutes as it enters the tubular cell via the apical membrane and subsequently actively transported out across the basolateral membrane. The filtrate remains isosmotic. Loop of Henle: Descending limb is freely permeable to water. The countercurrent exchange and multiplier arrangements of the vasa recta and the loop of Henle produce a hyperosmolar filtrate as water passively moves into the interstitium in the inner medullar. 20-25% of water is reabsorbed. Thick ascending limb impermeable to water (Na-K-2Cl co-transporter). In the distal convoluted tubule 5-10% of the filtrate is further reabsorbed passively down a concentration gradient driven by a Na+/K+ ATPase pump. In the collecting ducts under the influence of antidiuretic hormone (ADH) a further 1-3% of water can be reabsorbed.
• Growth hormone Growth hormone is synthesised by the somatotrophs of the anterior pituitary and it produces its effects mainly through IGF-1 produced by the liver. Production is controlled by the hypothalamic secretion of GHRH and somatostatin. Its effects include Anti-insulinic recruitment of glucose Anabolic effects and Lipolysis. It is also, in conjunction with priming of the anterior pituitary by sex hormones, responsible for the growth spurt during puberty.
• Hypophosphatämie The normal plasma range for phosphate is 0.8 - 1.45 mmol/l. Causes of hypophosphataemia include Hyperparathyroidism Osteomalacia Acute alkalosis (not acidosis) Haemodialysis, and Refeeding following prolonged starvation. The clinical manifestations of hypophosphataemia include Muscle weakness Respiratory failure Peripheral neuropathy Coma Seizures Rhabdomyolysis Haemolysis  Impaired platelet function. It is uncommon in children and is usually associated with malnutrition.

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