Jan Kirchhof


UMF Targu Mures

Physiology – Topics – UMF Targu Mures – 2012
Topic 1
Cell membrane – structure, types of membrane proteins    Organization: fluid mosaic lipid-protein model (1972 Singer, Nicolson)  fits on TD stability o Semi permeable lipid bilayer (hydrophilic heads outside, lipophilic tails inside) in which membrane proteins are inserted Chemical composition: 30% H2O, 70% organic substances (proteins + lipids  barrier: more lipids; metabolism: more proteins) Membrane proteins: o Ensure functionality:  Transporter (e.g. maintaining of ion conc.)  carrier proteins, channel proteins  Enzyme (protein synthesis)  adenylate cyclase  guanilate cyclase  phospholipase C  protein kinases A, C  Cell surface receptor (signal transmission, reaction with ligands  inducing special reactions inside the cell)  Adrenergic (react to symphatic neurotransmitter noradrenalin) o Alpha 1 receptors contraction of smooth muscles of vessels and bronchioles o Alpha 2 receptors contraction of smooth muscles of digestive sphincters o Beta 1 receptors stimulating effects on heart o Beta 2 receptors relaxation of smooth muscles of vessels and bronchioles  Cholinergic (react especially to acetylcholine) o Nicotinic receptors  stimulated by acetylcholine and nicotine  present at ganglionic synapses, neuromuscular junctions  blocked by curare o Muscarinic receptors  stimulated by acetylcholine and muscarine (Pilzgift)  present in end-organs (ACh released by postganglionic neurons/parasympathetic)  blocked by atropine  Cell adhesion (interacting/identifying between cells  cell identity marker  role in immune response)  Attachment to cytoskeleton o Intrinsic (peripheral) proteins  outside of bilayer (on outer or inner surface, often to integral proteins attached) o Extrinsic (integral) proteins  inside of bilayer (can be completely through membrane  transmembrane proteins)

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Jan Kirchhof


UMF Targu Mures

Topic 2
Mechanism of transport through cell membrane  Passive transport (no energy consumption, transport with/ down the conc. gradient) o Simple diffusion  Uncharged particles flow from higher to lower concentrations (speed depends on: permeability, lipid solubility)  lipophilic particles through lipid bilayer, hydrophilic ones through aquaporins o Facilitated diffusion by carrier proteins  High speeded transport for too large particles (e.g. glucose)  Transmembrane protein transporter/ carrier protein (specific for certain particle)  Can be coupled with other transport (e.g. sodium)  cotransport o Diffusion using channel proteins  Integral membrane proteins (bidirectional)  Ion channels (sodium, potassium, calcium channels) o Valtage-gated  opening depends on electrical gradient  Aquaporins (water channels) Active transport (energy consumption (ATP), transport against conc. gradient, optimal at 37°C)  Primary active transport (direct use of energy (ATP hydrolysis))  Sodium potassium pump (maintains resting potential): o ATP-ase (membrane protein) +  intracellular face: binds 3 Na to ATP  pumped out +  extracellular face: binds 2 K to ATP  pumped in +  secondary active transport (use of stored energy in Na conc. gradient)  made by carriers (integral membrane proteins)  uniport transport: single substance in certain direction  cotransport: transport of a substance is coupled with transport of another substance o symporters: 2 substrates in same direction (e.g. sodium glucose transporter) o antiporters: 2 substrates in different direction, using conc. gradient of one to drive the other Vesicular transport (transport of macromolecules):  Exocytosis: releasing proteins  Endocytosis: importing proteins by enclosing them in membrane  Phagocytosis (cell eating): immersion of solid substances  pinocytosis (cell drinking): immersion of liquid substances


Jan Kirchhof


UMF Targu Mures

Topic 3
Membrane potential  resting potential: o selective permeability of cell membrane:  inside (neg.): potassium ions, organic anions (macromolecules, cannot pass membrane)  outside (pos.): sodium ions, chloride ions o ions are asymmetrically distributed  causes membrane potential of -70 mV o many blablablablabla hier muss noch weitergemacht werden (s.28) Action potential: o Cell is in resting state and receives a signal (voltage variation) +  Membrane permeability changes  voltage gated Na channels open  sodium flows inward  inside becomes positive  If a certain threshold is reached  action potential (all or nothing, amplitudes same value, strengthen by frequency) o Depolarization phase (strong depolarization until +30 mV) +  All Na channels open + +  Na channels start closing, K channels start opening o Overshoot (amplitude is reached) o Repolarization phase: +  K channels opened  potassium flows out  inside gets back to resting potential  Sodium potassium pump restarts and renews resting potential o Hyperpolarization (-90 mV): 2+ + 2+  at depolarization Ca gets into cell  gets out at repolarization and keeps K channels open until Ca level is low  Sodium potassium pump renews resting potential o Resting potential is reached (process lasts 1-2 ms) Potentials can be measured by intracellular microelectrodes (recorded on oscilloscope)


Jan Kirchhof


UMF Targu Mures

Topic 4
Water content of the body and organs, water compartments, control of water intake  Water content: o Age:  fetus 100%  baby at birth 80%  adult 70%  elderly person 50% o organs:  brain 85%  heart 77%  lungs 80%  teeth 10%  liver 73%  bones 22%  kidneys 80%  muscle 73%  skin 71%  blood 79% o total body water (compartments):  intracellular 30-40%  Extracellular 16-20% (plasma 4%, interstitial 16%)  lymph, fluid around brain, plasma, joint fluid, fluid in stomach + intestines, blood  solid matter 40%  tissue, bone daily water requirements: 30-40ml/kg/day o sources (2500ml/day)  water drinking, food, metabolic water o losses (2500ml/day)  urine, feces, respiration, skin o pathological losses  bleeding, vomiting, diarrhea control of water intake: neuro hormonal mechanisms and sensation of thirst o osmoreceptors  thirst center  in hypothalamus  involved hormones:  ADH (antidiuretic hormone)  reduces water elimination by kidney (at night for not peeing in your pants)  Atrial natriuretic peptide  enhances renal elimination of sodium, sec. of water  Renin-angiotensin aldosterone system reduces renal elimination of sodium and water  Renin from kidney  ANG1  ANG2  thirst, production of aldosterone (reduce elimination)


usually legs  gravity) o causes:  reduced concentration of plasma proteins (loss. liver disorders). 6. 300 mOsm o Movement of water across capillary wall:  More permeable than cell membrane.  the higher the conc. diet deficiency)  increased capillary permeability (inflammation)  increased venous pressure  no balance between pressure gradients (heart failure. the higher the osmotic pressure o Physiologic solution: 5500 mmHg. reduced synthesis (kidney. membrane ruptures (H2O into cell) Osmotic pressure: o Generated by water movement from low to high conc. standing still)  blocked lymphatics (filarial worms (Fadenwürmer). impermeable for proteins  depends on balance between hydrostatic pressure and oncotic pressure (osmotic pressure of proteins) gradient edema: o accumulation (Anhäufung) of fluids in interstitium (swelling of parts of the body. causes of edema      Movement of H2O through semi permeable membrane to higher concentrated solution (influenced only by particles number) Isotonic solution: equal concentration of solutes (isotonic physiologic solution: 9gNaCl/l) Hypertonic solution: higher concentration of solutes  cells become wrinkled (H2O out of cell) Hypotonic solution: lower concentration of solutes  cells swell. removal of lymph vessels)  5 .7 atm.Jan Kirchhof Physiology UMF Targu Mures Topic 5 Osmosis and osmotic pressure.

high altitude (Höhe). alcoholic  keto acidosis. arrhythmia. of HCO3 and Ca (HCO3 + H  H2CO3  CO2 + H2O) o Metabolic alkalosis (HCO3 too high)  Caused by: vomiting (loss of HCl). angina     6 . coma. pH balance + pH: negative decadal logarithm of the amount of basic or acidic character due to the concentration of H in a solution of water o pH scale: 0-14  pH = 7  neutral +  pH < 7  acidic (high conc. fever. seizures. alkalosis  blood: fluid tissue (cells and plasma) o primary functions: transportation.4)  mechanisms to maintain the acid/base balance:  lungs expel CO2  kidneys eliminate acids in urine  skin secrets excess acids  plasma contains buffer that neutralize the pH buffer systems are a mixture of a weak acid and a conjugated base or vice versa that have a buffer capacity o blood buffer (total amount: 48 mEq/l):  bicarbonate/carbon dioxide buffer system (most important plasma buffer system – 75%)  HCO3 controlled (independent) in kidneys  CO2 controlled (independent) in lungs  Plasma bicarbonate: 22-26 mEq/l (at 40 mmHg pCO2)  Hb and OxiHb buffer (25%). nausea. buffers. lethargy (Schläfrigkeit).35-7. phosphate buffer (<1%) Acidosis (low blood pH.38 (7. of H ) +  pH > 7  basic (low conc. CNS lesion. disorder of 0. extreme exercise  lactic acid. thoracic or muscular disorder. fluid volume balance. cardiac arrest  Leads to: tremor (Zittern). tachycardia (Herzrasen). heat stress 2+ +  Leads to: low conc. anxiety. paralyzing agent o Metabolic acidosis (HCO3 too low)  Caused by: diarrhea. arrythhmia Alkalosis (high blood pH.2pH can lead to serious health consequences) o Respiratory alkalosis (CO2 too low)  Caused by: hyperventilation.2pH can lead to serious health consequences) o Respiratory acidosis (CO2 too high  too much CO2 production. acidosis. loss of acids in urine (diuretics). cushing syndrome  Leads to: confusion.Jan Kirchhof Physiology UMF Targu Mures Topic 6 Blood pH. too less CO2 excretion)  Caused by: airway obstruction. disorder of 0. exchange o secondary functions: immunity. thermoregulation. hypotension. pulmonary disease. of H ) o blood plasma and body fluids pH: 7. diabetic. renal failure. aldosterism.

2. control of blood volume  Blood volume: 2 o 5-6 liter (depends on body volume and gender  76 ml/kg.Jan Kirchhof Physiology UMF Targu Mures Topic 7 Blood volume. hematocrit.6 liter/m ) o Composition:  Plasma (55%)  Cells (45%)  White blood cells and platelets (<1%)  Red blood cells (45%) Hematocrit (ratio between blood cells and plasma  hematokrit = red cells / total): o Males: 42-50% o Females: 39-48% Control of blood volume: o Body functions controlled by vegetative nervous system and endocrine glands o Physiological blood volume control mechanisms:  Control of fluids and electrolytes  by kidneys  Control of cardiac output  by heart  Control of arterial blood pressure  by vessels  Control of erythropoiesis  by kidneys  Control of protein synthesis  by liver o Increased blood volume leads to:  Reduces secretion of ADH and aldosterone  renal elimination of water and sodium is increased  Increases blood pressure  high hydrostatic pressure  forces H2O to interstitium  increases glomerular filtration  Stimulates secretion of atrial natriuretic peptide (ANP/Herzvorhof-Faktor)  increases elimination of water and sodium  Causes dilatation of blood vessels (because reduced sympathetic activity)   7 .

maintenance of water balance (osmotic pressure gradient. their roles.) o Controlling concentration by active transport not really sure Plasma anion gap: o Important for diagnosis of metabolic acidosis + + o Calculation: AG = ([Na ]+[K ])-([Cl ]+[HCO3 ]) o VN(AG) = 12 (higher values if loss of HCO3. blood pH) + o Na + Cl  maintain osmotic pressure o HCO3  maintains blood pH (component of major buffer system) 2+ o Ca  role in: o neuro-muscular excitability (Erregbarkeit) o muscular contraction o blood coagulation o bone metabolism together with phosphates 2+ o activation of enzymes together with Mg 2+ 2+ o Fe + Cu  role in erythropoesis o I  component of thyroid hormones Balance of electrolytes o Maintaining balance with food + intestinal absorption and elimination.and no equalization by Cl )    8 .5 mmol  Anions (150 mmol)  HCO3 27 mmol  Cl 103 mmol  Proteins Role of electrocytes: o General: important for function of muscle and nerve cells. globulins. regulated by hormones (ADH. etc.Jan Kirchhof Physiology UMF Targu Mures Topic 8 Plasma electrolytes. fibrinogen) o Gases o Nitrogenous waste o Electrolytes (1 g/dl. anion gap  Content of plasma (90% H2O): o Amino acids o Proteins (albumins. 300 mmol/liter)  Cations (150 mmol) +  Na 143 mmol +  K 5 mmol 2+  Ca 2. aldosteron.

drugs 2+ o Binds Ca o Buffers pH Globulins: o Molecular mass: 90-1300 kDa o Produced in liver and immune system o Isolated by electrophoresis in: alpha 1. ceruloplasmin (Cu) o Glycoproteins (carrying carbohydrates): immunoglobulins (IgA. pole (in order mentioned above)) Albumin: o Molecular mass: 67 kDa o Most abundant (häufigestes)  >55% o Produced in liver o Maintains oncotic pressure o Transports: hormones. alpha 2. drugs) o Defence (globulins: immunoglobulins. complement. carbohydrates. obstacles in biliary tract  cause jaundice/icterus (test only on blood test. blood coagulation. gamma o Transport substances o Enzymatic active o Defensive role (immunoglobulins) Classification due to carried substances o Metalloproteins (carrying metals): transferin (Fe).8 mg /dl) o Final product of Hb metabolism o High values  in hepatis. enzymes o Seperation by electrophoresis (alkaline solution  proteins become neg. hormones. renal insufficiency. IgG. beta 1.6 mM) o Final product of protein metabolism o High value  hepatic insufficiency o Low value  ureamia in acute nephritis. kidney.3-6. fatty acids. lipids. roles   Plasma proteins (6-8 g/dl blood. reactive C protein) o Maintenance erythrocyte sedimentation rate o Enzymes (activation and inhibition of proteolysis (Proteinabbau). by globulins: ions. fibrinogen. gamma). IgM. IDLP.IgE) o Lipoproteins (carrying lipids): chylomicrons.Jan Kirchhof Physiology UMF Targu Mures Topic 9 Plasma proteins: classification.2-0. excessive hemolysis. creatine o Product of muscular metabolism o Synthesized in liver. beta 2. beta. after normal blood values skin is 4 more days yellow)    9 . fibrinolysis (Gerinnselauflösung))    Nonprotein nitrogenous compounds in plasma  Urea/Harnstoff (20-40 mg/dl. VLDL. pancreas Uric acid/Harnsäure (3-6 mg/dl) o Final product of nucleoprotein metabolism o High value  in gout/Gicht (disease affecting small articulation  urate crystals are deposited) Bilirubin (0. properdin. synthesis of 15 g/day in liver): albumin. 3. HDL (due to density) Roles of plasma proteins: o Maintenance of oncotic pressure (albumin) o Maintenance of pH (albumin) o Transport (espec. charged  go to pos. bilirubin. LDL. globulin (alpha. hormones. can cause coma Creatinine.

diet. tissue desensitizes to insulin. amino acids + lactic acid + fats (neoglucogenesis) o Liver is mainly involved in glucose production o Hyperglucaemiant (increase glycaemia) :  Food  Glucagon (alpha-pancreas)  Growth hormone  ACTH (Adrenocorticotropin hormone) stimulates synthesis of glucocorticoids  Thyroid hormones o Hypoglucaemiant (decrease glycaemia):  insulin (beta-pancreas) (normal glycaemia after 2h) o Diabetes Mellitus (fasting glycaemia >126 mg/dl.4-5. but not enough relative to body mass and glycaemia o no absolute but rather deficiency  beta cells get tired. obesity. cardiac infarction)  microangiopathy (kidney – nephro-. daily glycaemia >200 mg/dl)  failure in forming or utilizing (nutzen) insulin  leads to hyperglycaemia)  diabetes. 4. physical activity are important factors  beta cells produce enough insulin. does not take up glucose properly  insulin resistence  gestational diabetes  sometimes at women in pregnancy 10 . high cholesterol + keton bodies)  type 1 DM (IDDM)  insulin dependent DM  autoimmune disease  antibodies result beta cell destruction (only 5% survive)  failure of producing insulin  type 2 DM  insulin independent DM  obesity. nerves – neuropathy.Jan Kirchhof Physiology UMF Targu Mures Topic 10 Blood sugars  Glucose (main blood sugar) o VN (glycaemia): 80-100 mg/dl.5 mM/liter o Source: food. eyes – retino-. glycogen (glycogenolysis). arterial hypertension  risk factor for cardiovascular disease  complications:  macroangiopathy (arteriosclerosis  stroke.

9 o Overweight 25 – 29. fatty acids. country) Lipoproteins are transporter for blood fats o Made of lipids bound to proteins (especially globulins) forming globular micelle particles o Present a hydrophil surface: phospholipids. but when too much  deposits on vascular walls  atherosclerosis o VN (chol. apolipoproteins (transports hydrophob lipids). beta globulins (by electrophoresis)  Due to density (by ultracentrifugation)  in this order quantity of fat decreases. quantity of protein increases  Chylomicrons  Very low density LP (VLDL)  Intermediate density LP (IDL)  Low density (LDL) (“bad cholesterol”. collects cholesterol from tissue.5 – 24.7 mmol (but differences in age. carries cholesterol from liver to the cells)  High density (HDL) (“good cholesterol”.5 o Normal weight 18.9 o Obesity > 30 Waist circumference should be: o men < 90 o women < 80   11 .6-5. cholesterol o Present a hydrophob core: triglycerides.Jan Kirchhof Physiology UMF Targu Mures Topic 11 Blood fats      triglycerides. 2. sex. cholesterol esters o Classification:  Alpha. phospholipids. bringing it to liver) 2 2 Body mass index (BMI = weight [kg] / height [m ]) o Underweight < 18. cholesterol VN (blood fats/lipids): 700-800 mg/dl High levels of blood lipids are a risk factor for cardiovascular disease ( amount of cholesterol is considered as an index of risk) Cholesterol is important for body functions. diet.): 100-220 mg/dl.

role of iron  erythrocytes (red blood cells) o formed in the red bone marrow  erythropoiesis  controlled by erythropoietin (EPO)(hormone)  synthesized by kidney (. EPO acts on E-progenitor (Vorläufer) cells in bone marrow  production of new erythrocytes  3. no physiological excretion o VN (iron in serum):  Men: 65 – 175 µg/dl  Women : 50 – 170 µg/dl  Children: 50 – 120 µg/dl o Symptoms of iron deficiency:  Lethargy. proliferation o Erythrocytes contain iron in form of Hb oxygen carrier o 3-4 g iron in the body  10-20 mg/day intake (diet)  1 mg/day (absorption in duodenum and upper jejunum) 3+ 2+  Entering duodenal membrane: Fe  Fe (ferri reductase)  In duodenal membrane: passing membrane or binding to ferritin to be stored 2+ 3+  Exiting duodenal membrane: Fe  Fe (ferri oxidase). erythropoietin. cellular growth. cardiorespiratory disturbance  Impaired cognition (beeinträchtigte Wahrnehmung)  Impaired immune system  Endocrine. weakness. Kidney senses hypoxia (anemia)  increases endogenous EPO production  2.liver) when too less O2 in blood (altitude training)  1. headache  Angina.Jan Kirchhof Physiology UMF Targu Mures Topic 12 Erythropoiesis. depression. Kidney senses increased tissue oxygenation  decreases EPO production Erythropoiesis: o Hemocytoblast (stem cell)  at division remains one stem cell. binding to transferrin for transport  transport in blood by transferrin (globulin)  75% bound to Hb. 10-20% stored in liver and heart bound to ferritin. shortness of breath. the other becomes the precursor cell o Proerythroblast (committed cell/Vorläuferzelle) o Early erythroblast  phase 1: ribosome synthesis o Late erythroblast  phase 2: hemoglobin accumulation(Anhäufung) o Normoblast  phase 3: ejection of nucleus o Reticulucyte (youthful erythrocytes) o Erythrocyte Role of iron in the body: o Necessary for energy production of cells. metabolic disorders  Gastrointestinal disturbance Other nutrients important for erythropoiesis: o Vitamin B12 (size and function of erythrocytes) o Folate (vitamin B9) o Copper    12 . fatigue (Müdigkeit).

number.5 %)) o 1% destroyed per day by agglutination and hemolysis  80% in spleen      13 . sex (greater in males).Jan Kirchhof Physiology UMF Targu Mures Topic 13 Characteristics of erythrocytes: dimension.5 – 1.3-Diphosphoglycerate  binds to tensed form of Hb  lowers O2 affinity (O2 is emitted at higher partial pressures of CO2) Lifespan: o 120 days (youthful erythrocytes called: reticulocytes (0. altitude  Reduced number: characteristic of anemia  Increased number: poliglugolia  Different size and shape: category of anemia  Anisocytosis  size: <7 µm or >10 µm  Poikilocytosis  shape  Modifications can be observed with microscopes Properties: o Highly deformable  visco elastic property of membrane  important for circulation in small vessels Composition: o H2O: 57% -12 o Hb: 33% (30 pg or 30*10 g) o Lipids: 7% o Sugar: 3% Enzymes playing a role in erythrocytes metabolic activity: o Carbonic anhydrase  CO2 transport o 2. composition. lifespan  Dimension: o Disc diameter: 7 µm o Thickness: 2 µm 3 o Volume: 85 µm 2 o Surface: 125 µm 2 o Total surface: 3000 µm Number of erythrocytes: 12 o 4-6*10 /liter (physiological variations due to age (greater in newborn).

A.persons develop antibodies (anti D) at first time  anti D reacts with Rh+ blood at second time  destruction  Prevent sensitization at pregnancy: give mother 72h after birth Rh immune globuline o destroys Rh+ erythrocytes.patient  Rh. AB o Erythrocyte surfaces present antigenic determinants  antigens o Blood plasma presents opposite antibodies of blood group o Erythrocytes agglutinate if antigen and corresponding antibody come together (A with alpha. and B Rhesus system: o 85% (white people. 96% black) are Rh+ (have system) o 15% are Rho Rh antigen has many components: C.Jan Kirchhof Physiology UMF Targu Mures Topic 14 Blood groups: AB0 system. c. Rhesus system  AB0 system (by Landsteiner): o 4 main blood groups: 0. e  most powerful: D  Presence of antigen D (or D + another)  Rh+  Presence of other antigens  Rho 2 cases of risks::  Second transfusion with Rh+ blood to Rh. E. B with beta) o Group 0 (45%): no antigen antibody alpha and beta no agglutination o Group A (40%): antigen A antibody beta agglutination with group 0 and B o Group B (11%): antigen B antibody alpha agglutination with 0 and A o Group AB (4%): antigen A and B no antibody agglutination with 0. d. B. A. before she produces antibodies blood transfusions only permitted with Rh and AB0 compatibility (some blood group and Rhesus factor)   14 .mother with Rh+ fetus (at second pregnancy)  risk of erythroblastosis fetalis  Rh. D.

2 – 1. instead HbA2. bone marrow  rupturing of cell membrane): o Hb is degraded to:  Globin  recycled  Heme is degraded to:  Iron  recycled  Biliverdin is reduced to: o Bilirubin is bound to albumin o forming complex albumin-unconjugated/indirect bilirubin o  goes to liver where complex is broken o  bilirubin is recombined with glucoronic acid o  forming conjugated/direct bilirubin o  excreted in bile going to small intestine.0 mg/dl  > 2 mg/dl  icterus/jaundice (yellow colored skin and conjunctiva (Bindehaut))  excessive hemolysis (increased bilirubin production over liver’s capacity)  prehepatic  hepatic disease (decreased bilirubin uptake by the liver)  hepatic  obstacles on bilary truct (white stool  operate quick)  posthepatic     15 . disorders  Hb is red colored protein. porphyrine ring. transformed to:  Stercobilinogen and stercobilin   partially excreted (color of stool)   partially reabsorbed (excreted by kidney)  Urobilinogen and urobiln (color of urine) o Total amount of bilirubin in blood: 0. structure.5 – 16. HbF  instability of erythrocytes  quick destruction  inefficient erythropoiesis  chronic anemia  especially in mediterranean zone o Sickle cell disease:  Abnormal structure of globin chain (beta6 glutamine is exchanged with valine)  forming HbS (sickle)  erythrocytes are sickle shaped. have reduced resistance more hemolysis (excreted in urine  red color)  multiple organ infarcts (thrombosis) Red blood cell destruction (in spleen.Jan Kirchhof Physiology UMF Targu Mures Topic 15 Hemoglobin: quantity. beta.8 mg/dl o VN (bilirubin in blood) = 0. made by heme (synthesized in mitochondria) and globin (synthesized in ribosomes) o Globin: 4 polypeptide chains (alpha. liver. delta)  3 types of Hb due to the polypeptide chains:  A1 2 alpha + 2 beta dominant Hb at age of one year  A2 2 alpha + 2 delta  F 2 alpha + 2 gamma fetal Hb o Heme (4): tetrapyloric structure. capacity to carry oxygen)  hemoglobinopaties: o Thalasemia (recessive hereditary disease):  Deficiency in globin chain production: no or less production of beta chains  no HbA1. gamma.34 ml O2  1 liter blood can carry 2 dl O2 (5 liter blood = 1 liter O2) Hemoglobin disorders (modification of structure. but more volume) o  1 g Hb can combine with 1. contains iron. shape.5 g/dl o Women 12 – 15 g/dl o Children 11 – 16 g/dl o Pregnant women 11 – 12 g/dl (some amount of Hb. can bind one O2 molecule 8 Each erythrocyte contains 3*10 Hb molecules (88% of erythrocyte) Total amount of Hb in blood: o Men 13.

they do not have MetHb reductase sulfhemoglobin SHb o stable combination of Hb and sulfur o no carriage of oxygen o occurs when Hb is exposed to some drugs (phenacetin.3 – DPG  stabilizes T – form. 20 ml O2 / 100 ml blood (98% saturation. sulfonamides) relationship of Hb binding O2 o arterial blood: ca. 5%)  10%  impaired judgement  50%  unconsciousness (risk of death)  CO poisoning: reddish skin o Withdraw CO from Hb with high partial pressure of O2 (increases O2 affinity) methemoglobin MetHb 2+ 3+ o Fe  Fe (oxidation): cannot bind to oxygen o VN (MetHb/Hb) = 0 – 3%  higher values lead to cyanosis (can be caused by nitrates from water)  dangerous for babies. appr. because some venous blood) o factors increasing Hb affinity binding O2 (at lungs):  low temperature (in lungs)  weak basic pH.Jan Kirchhof Physiology UMF Targu Mures Topic 16 Compounds of hemoglobin  oxyhemoglobin O2Hb o labile combination Hb and oxygen  major form of oxygen transport in arterial blood o each Hb can bind 4 O2 molecules reduced Hemoglobin HHb + o deoxyHb: O2Hb  HHb + O2 + K o present in venous blood (3 g/dl. low pCO2  Bohr effect o factors decreasing Hb affinity binding O2 (in tissues):  high temperature (in tissues)  weak acidic pH. if amount increases to 4-5 g/dl  cyanosis (bluish lips and fingers)) carbaminohemoglobin CO2Hb o labile combination Hb and carbondioxide  form of CO2 transport in the blood carboxyhemoglobin COHb o stable combination of Hb and CO (great affinity of Hb to CO) o VN (COHb/Hb) < 1% (levels of city people and smokers are higher. O2 emission)       16 . high pCO2  Bohr effect  2.3 – DPG (tensed state of Hb takes 2.

number increased at parasitic worm infection Basophils (1% of leucos) o Staining: cytoplasmic lysosomal granules are stained basic blue o Nuclei: large. unlobed. proliferation by IL5) o Staining: cytoplasmic lysosomal granules are stained acidic red (eosin) o Nuclei: large. kidney-bean shape o 20 µm cell diameter (largest leucocyte) o Role:  Interact with lymphocytes  recognize and destroy foreign bodies  Stimulus: transformed to macrophages (200 µm)  Production of substances for immune response (ILs. monocytes)  Immunocytes (lymphocytes) Neutrophils (60% of leucos. basophil  lymphoblast (committed cell)  lymphocyte   stimulated by several growth factors/colony stimulating factors (CSF)  cytokines/interleukins (IL) Classification: o Form of nucleus (morphologic):  Polymorphonuclear cells (PMN) (neutrophils. two connected lobes o 12-14 µm cell diameter o Role: involved in allergies. interferons. lymphocytes) o Presence of granulations (morphologic):  Granulocytes (neutrophils. pinched in several lobes (metamyelocyte. inflammation process. growth factors. eosinophils (like acids). eosinophils. basophils (like basics))  Mononuclear cells (monocytes. lymphocytes) o Functions:  Phagocytes (neutrophils. classification. involved in allergies (bronchial asthma by histamin) Monocytes (6% of leucos) o Nuclei: large. inflammation process Eosinophils (3% of leucos. non-segmented. sometimes 3 lobes o 11-13 µm cell diameter o Role: production of heparin (anticoagulant). surrounded by thin rim of cytoplasm o 7-8 µm diameter (small) o Role: crucial (entscheidende) role in immune response       17 . basophils. toxic radicals)  Present antigens to lymphocytes and have MHC (major histocompatibility complex) Lymphocytes (30% of leucos) o Nuclei: round. basophils)  Agranulocytes (monocytes. segmented neutrophil) o 12 µm cell diameter o Role: destroy foreign invaders (bacteria) by enzymes of lysosomal granules.Jan Kirchhof Physiology UMF Targu Mures Topic 17 Leucocytes: number. proliferation by IL1): o Staining: cytoplasmic lysosomal granules are stained by acidic and basic mildy o Nuclei: elongated. eosinophil. leucocytic formula  Leucocytes (white blood cells): o Nucleated blood cells. eosinophils. irregular. role in defense mechanisms 3 o VN = 6000 – 8000 / mm o leucopoieses (formation) in bone marrow:  hemocytoblast (stem cell)  monoblast (committed cell)  monocyte  myeloblast (committed cell)  promyelocyte/granulocyte  neutrophil.

classification. distinguishable by specific markers (CD) T-cells (matured in thymus (T). roles   Both types are produced in bone marrow. natural killer T-cells o T suppressor (unterdrücken) cells (CD5 marker)  reduce activity of killer T-cells o T cytotoxic/killer cells (CD8 marker)  can kill all foreign recognized cells (cancer. interferons o T natural killer cells  front line soldier  kill directly any non-self cell without B-/T-cell action B-cells (matured in bone marrow (B)) o Stimulus: transformed in plasmocytes  they secrete antibodies/immunoglobins  react with specific antigens  18 . recognize antigens in antigen presenting cells): o T helper/inducer cells (CD4 marker)  stimulate activity of B-cells. tumor necrose factor.Jan Kirchhof Physiology UMF Targu Mures Topic 18 Lymphocytes B and T. cytotoxic T-cells. transplanted)  secrete: perforins. suppressor cells o T amplifier (verstärken) cells (CD4 marker)  stimulate activity of cytotoxic T-cells. virus infected.

beta. monocytes-macrophages (big eaters) o proteins:  interferons (alpha. eosinophils. fungi destroying them  lisozyme  present in saliva and tears  destroys cell membrane of bacteria  reactive C protein (globulin)  activates complement proteins  facilitates opsonization and phagocytosis 19 . basophils. gamma)  produced when cell is infected by virus  protect other cells around  resistance is short termed (one week)  complement proteins (have to be activated)  produced by liver  coat surface of microbe (opsonization)  facilitate identifying + engulfing (verschlingen) for macrophage  membrane attack complex (MAC)  form holes in microbe’s cell membrane  death of microbe  properidin  act with activated complement proteins  on microbes.Jan Kirchhof Physiology UMF Targu Mures Topic 19 Substances involved in the nonspecific body defense  non specific body defense belongs to the second line  immediate response involving: o phagocytes (neutrophils.

IL 10. activate tissue repair cells  7. tryptase  Eosinophils  leukotrien. IL 4  T-cells  IL 4. Phagocyte discharges waste material Inflammatory response (major part of non-specific defense system) o Activated by tissue damage (microbes. wound is repaired o Inflammatory signs:  Heat  Redness  Pain  Swelling  20 . Inflammatory response lasts until foreign material is eliminated. viruses) by leucocytes o steps:  1. Mast cells secrete factors mediate vasodilation + vascular constriction  more blood. Digestion of ingested microbe by enzymes  6. Neutrophils and macrophages remove pathogens  phagocytosis  6. IL 5. fungi. physical agents) o Effector-cells secrete mediators (involved in defense processes)  Mast cells  histamine.Jan Kirchhof Physiology UMF Targu Mures Topic 20 Phagocytosis and inflammatory response  Phagocytosis (part of non-specific defense system) o engulfing pathogens (bacteria. prostaglandine E2. Platelets release blood-clotting proteins at wound  3. IL 13 o Steps:  1. Formation of phagosome (phagocytic vesicle)  4.EDN. Adherence of microbe to phagocyte  2. Fusion of phagosome with lysosome (contains digestive enzymes)  forming phagolysosome  5. IL 13  Basophils  histamine. Pathogens enter wound  2. insects bites. plasma. Formation of residual body containing indigestible material  7. Macrophages secrete cytokines (hormone)  attract immune system cells to wound. ECP. prostaglandin E2. leukotrien C4. IL 4. Ingestion of microbe in phagocyte  3. TGF-beta. IL 5. Neutrophils secrete factors  kill and degrade pathogens  5. cells at wound  4.

viruses. MHC-complex is transported to cell surface by golgi apparatus  5. fungi.Jan Kirchhof Physiology UMF Targu Mures Topic 21 Types of immunity. Antigen (from pathogen) enters dendritic cell  2.and T-cells  Antigen presentation:  1. prions)  Immune tolerance: B-. active (immunization  vaccine)  21 . active (infection)  Artificial: passive (antibody transfer  serum). MHC  MHC (major histocompatibility complex): o Present in all body cells o MHC proteins belong to HLA (human leucocyte antigen) system  unique for an individual o MHC proteins present antigens (from pathogens) to B. antigen is breaken down  3. T-cells ignore own tissue considered as own tissue  Antigen  recognized by immune system as foreign  induce formation of antibodies  Antibodies (gamma globulins  immunoglobulins)  produced by plasma at stimulus from B-cells  Vaccines (contain killed microbes  antigens)  induce immune response  forming own antibodies  long term  Serums (contains antibodies)  act immediately  short term protection o Two types:  Innate (angeborene) immunity (non specific)  Natural resistence  Acts like barrier  Use process of inflammatory response  Adaptive/acquired (erworbene) immunity  Natural: passive (maternal). protozoa. MHC protein presents antigen in cell surface o Class I MHC (intracellular):  Presents antigens found inside of infected cell to cytotoxic T-cells (CD8)  Cytotoxic T-cells identify these infected cells and eliminate them  cellular immune response o Class II MHC (extracellular):  Presents antigens found outside the cell to helper T-cell (CD4)  Helper T-cell produces specific antibodies and stimulates activity of certain phagocytes o Phagocytes inactivate the extracellular pathogens and eliminate them  humoral immune response Immunity: o Introduction:  System that defends the body against pathogens (bacteria. these pieces bind to MHC protein in ER  4.

basophils) o secrete histamine. leucotrienes  act especially on smooth muscles  examples: urticaria (Nesselausschlag). allergic rhinitis (hay fever). bronchial asthma. anaphylaxis Cellular immune response (intracellular): o Based on action of T-cells (due to stimulus after contact with antigen presenting cell) o Autoimmunity: lymphocytes recognize own body cells as foreign/non-self  destruction of own cells o AIDS (acquired immune deficiency syndrome)  HIV (human immunodeficiency virus) destroys helper T-cells  depressed immune system  22 .Jan Kirchhof Physiology UMF Targu Mures Topic 22 The humoral immune response and cellular immune response  Humoral immune response (extracellular): o Based on production of antibodies by plasma cells (due to stimulus of B-cells)  Antibodies destroy antigens (activate complement proteins) o Humoral response in allergies:  Allergies are exaggerated responses at second meeting with an antigen  After first meeting: antibodies (IgE) are produced in high quantity  bind to effector cells (mastocytes.

thrombospondin. lymphocytes o Influence plaque progression  blood clots  blockade  heart. 2 – 3 µm diameter 3 o VN = 150000 – 300000 / mm o Lifespan: 8 – 10 days o thrombopoiesis (formation) in bone marrow  hemocytoblast (stem cell)  megakaryoblast  promegakaryocyte megakaryocyte platelets (approximately 8000 per megakaryocyte) o components:  canalicular system  alpha granule (contain Willebrand Factor (vWF). morphological characteristics. serotonin. inactivity  Antiplatelet agents can prevent arterial wall damage  Disorder of platelet quantity or quality  spontaneous bleedings  Thrombocytopenia (reduced quantity)  blood seeps in tissue  purpura (purple blotches (blaue Flecken))  Glanzmann’s thrombasthenia (hereditary): poor quality. ADP. Ca . DM. brain damage  Causes of arterial wall damage: high cholesterol.) in inner lining of artery o Creates plaque o Reduces blood flow  Activated platelets are involved at damage of endothelial lining and atherosclerotic lesion o interacting with monocytes. disorders  Thrombocytes (platelets): o anucleated (kernlos) o disc shaped fragements. thrombin. etc. growth)  irreversible o Coagulation reaction is promoted  platelet activation + coagulation  red clot o Disorders:  Atherosclerosis 2+  Building up of deposits (fatty substances. growth factors)  microtubules  glycogen  mitochondria 2+  dense body (contain ADP. fibrinogen)  Fibrin strengthens structure  platelet aggregation (thrombus formation. waste. obesity. vWF) o function:  scanning vascular system. smoking. Ca . respond to endothelial damage  bind to injuries (in seconds)  component of clotting system  platelet activation (when binding to injuries): o Exocytosis of dense granules and alpha granules o Activation of phospholipase A2 (membrane enzyme)  formation of thromboxane A2 (TXA2) o Shape change (projecting fingers)  reversible o Adhesion between platelets and collagen under endothelium  forming platelet plug (white clot)  Supported by receptors (vWF. cholesterol. serotonin)  microfilaments  surface glycoproteins (receptors for collagen. hypertony. disorder in GP IIb/IIIa (receptor) production o excessive bleeding 23 .Jan Kirchhof Physiology UMF Targu Mures Topic 23 Thrombocytes/Platelets: number. functions.

formation of fibrin mesh  coagulation of blood  fibrinogen is transformed to fibrin  forms a mesh over blood cells (red thrombus)  4. D. stent))    24 .Jan Kirchhof Physiology UMF Targu Mures Topic 24 Hemostasis: phases. vascular constriction  induced by pain (caused by injury) and vasoconstrictive substances (serotonin) by platelets  2. liver disease  Overwhelmed action of anticoagulant and fibrinolytic systems o  microthrombi. dissolution of the clot  Fibrinolysis destruction of fibrin filaments with the action of plasmin (protease) o Fibrin degradation products are E. snake bites. b) mechanical removal (angioplasty (balloon. disorders  hemostasis is the process that stops bleeding o primary/cellular hemostasis  1. consumption of platelets and coagulation factors and anticoagulants   severe bleeding o Clotting (risk for thrombosis)  Arterial/venous thrombosis:  Can lead to obstruction or mobilization of thrombi in blood vessels (embolism)  Medical treatment: deobstruct vessels  a) dissolve clot. activation. pregnancy complications. aggregation o secondary/plasmatic hemostasis  3. intervention of platelets  adhesion. tissue ischemia (Minderdurchblutung). Y fibrinopeptides medical practice o Not physiological fibrinolysis (dissolve intravascular clots):  Streptokinase (produced by streptococcus bacteria)  activates plasminogen to plasmin  activates fibrinolysis o Not physiological inhibiting of fibrinolysis (prevention of excessive blood loss during operation)  Aprotinin (trasylol) (from bovine (Rinder) lungs) Hemostatic and fibrinolytic system are balanced due to cooperation of activating and suppressing enzymes Disorders: o Hemorrhage (risk for bleeding)  Hemophilia (inherited disorder): deficiency of any clotting factors (most F VIII)  excessive bleeding  DIC (disseminated intravascular coagulation):  Caused by: massive tissue damage. cancer. sepsis. X.

IX. fibrin  pathways are series of reactins where enzymes + cofactors are activated and catalyze next reaction  learn picture of the book 2 pages after clotting factors o anticoagulants (inhibit coagulation)  natural anticoagulants:  heparin o produced in liver and lung (from basophils and mastocytes) o inhibits activity of thrombin o acts fast but not long  for acute problem  antithrombin III o inhibits activated II. VIII o Facilitates intravasacular clot lysis  Extrinsic anticoagulants:  Coumadin (inhibits vitK  no synthesis of II. X) 2+  Citrates (binds Ca )  Hirudin (blocking thrombin) 25 . of cascade  feedback mech. kallicrein. X need vitamin K for synthesis o Coagulation cascade:  Initiated by 2 pathways:  Contact activation pathway /small endothelial damage (intrinsic)  Tissue factor pathway / tissue damage (extrinsic)  both activate final common pathway of factor X. VII. thrombin (most imp. IX.). anticoagulants  Coagulation: o Enzymatic process: fibrinogen is transformed in fibrin that forms a mesh entrapping the blood cells (red thrombus)  Controlled by intervention of clotting factors: o Factor I fibrinogen o Factor II prothrombin o Factor III tissue thromboplsatin o Factor IV calcium ions o Factor V labile factor o Factor VII stable factor o Factor VIII antihemophilic factor o Factor IX Christmas factor/plasma thromboplastin component (PTC) o Factor X Stuart-Prower factor o Factor XI plasma thromboplastin antecedent (PTA) o Factor XII Hageman factor o Factor XIII fibrin stabilizing factor  Most of them are glycoproteins (globulins)  formed in liver  Factor II. subst.Jan Kirchhof Physiology UMF Targu Mures Topic 25 Coagulation of blood. plasmin. VII o heparin amplifies action  Protein C + S o Produced in liver with VitK o Inhibits activated V. clotting factors. XII. IX. X. XI. VII.

component of the nephron  Kidney: o Primary organ of homeostasis (Aufrechterhaltung des Gleichgewichts) of:  Volume of body fluids  Composition of body fluids  Excretion of metabolic waste in the urine o Anatomy:  Large. in cortex or medulla. protected by renal capsule (tough fibrous coat)  Urinary system (way of urine): kidney  ureter  urinary bladder  urethra  outside  Components (longitudinal section):  Cortex (low πb)  surrounds pyramids (darker. situated at dorsal side of visceral cavity. triangular structures)  Medulla (high πb)  made by pyramids  Renal pelvis (inner part of kidney)  collects urine from calyces  drains in ureter 6 Nephron: basic functional unit of kidney (approximately 10 in kidney.Jan Kirchhof Physiology UMF Targu Mures Topic 26 Kidney anatomy. depends on length  continued by…)  loop in medulla: juxtamedullary nephron (15%)  loop in cortex: cortical nephron o Distal convoluted tubule (situated in cortex  continued by…) o Collecting tubule (goes in medulla  continued by ureter)  26 . 90% have to work for proper function) o Glomerulus + Bowman’s capsule  form renal corpuscle (situated in cortex  continued by…) o Proximal convoluted tubule (situated in cortex  continued by…) o Loop of Henle (u-shaped) (sit. bean shaped organ.

HP in mmHg (hydrostatic pressure). 4 ml/min/g) one of highest blood flow values o Renal veins drain blood of kidney in vena cava inferior o Pressures: (values are inaccurate. pressures  Blood supply: o Renal artery  Receive approximately 20% of cardiac output (ca. πb in mmHg (oncotic pressure))  Arteria renalis HP 100 πb 30  Afferent arteriole HP 100-60 πb 30  Glomerular capillary HP 60 πb 30-35  Efferent arteriole HP 60-25 πb 35  meeting point of two curves  Peritubular capillary HP 25 πb 35-30  Infrarenal vein HP 25-10 πb 30  Vena renalis HP 10-5 πb 30  Afferent + efferent arterioles are major resistence sites  major sites for RBF (renal blood flow) control  If HP > πb  filtration (glomerular capillaries)  If πb > HP  reabsorbtion (peritubular capillaries) 27 .Jan Kirchhof Physiology UMF Targu Mures Topic 27 Renal blood flow.

Jan Kirchhof Physiology UMF Targu Mures Topic 28 Mechanisms of urine formation  mechanisms: o Glomerular filtration (blood plasma) at glomerulus  from vessels to renal interstitial fluid (primary urine) o Tubular reabsorbtion of water and solutes at prox. conv. tubules  from vessels to interstitial fluids Nephrons receive blood by afferent arterioles  entering glomerulus Blood leaves glomerulus by efferent arterioles o High vascular resistance  low pressure in peritubular capillaries  reabsorbtion (H2O and solutes from renal interstitial fluid) o 90 – 95% of postglomerular RBF: perfuses renal cortex o 5 – 10% of postglomerular RBF: perfuses renal medulla  vasa recta o 1% of postglomerular RBF: perfuses inner medulla that serves medullary osmolar gradient   28 . tubules  from renal interstitial fluid to vessels o Tubular secretion at distal conv.

papaverine)   29 . if: damage. GFR o Constriction of afferent arteriole   high afferent resistance   lower pressure in glomerular capillaries (lower filtration pressure) o  lower GFR o Constriction of efferent arteriole   opposite effects RBF/GFR regulation (autoregulation. RPF. concept of clearance    Glomerulus is surrounded by Bowman’s capsule  presents capillaries inside (podocytes around  cytoplasmic extension for filtration Capillaries are very permeable to plasma  large portion filtered from blood o Proteins are not filtered. ADH. serotonin  Hormones for vasodilation: prostaglandins. angiotensin. nervous regulation. natriuretic peptide. proteinuria. glomerulopathy Amount of filtered plasma depends on:  Capillary hydrostatic pressure 55 mmHg  Blood oncotic/ colloid osmotic pressure -30 mm Hg  Capsular hydrostatic pressure -15 mmHg  Capsular oncotic/ colloid osmotic pressure 0 mmHg o  +10mmHg towards outside  RBF (renal blood flow): 1250 ml/min  RPF (renal plasma flow): 650 ml/min  GFR (Glomerular filtration rate): 125 ml/min (10/55 * 650 ml) Resistance of afferent and efferent arterioles important for RBF. too big (>10µm). adrenalin. bradykinin. humoral regulation) o Autoregulation:  Can maintains RBF. GFR in blood pressures between 80 – 200 mmHg (in absence of neural/humoral factors)  Starts through myogenic response  Outside of 80 – 200 mmHg more pressure dependent  less than 40 mmHg severely reduced GFR o Sympathetic nerves:  Acts on afferent and efferent arterioles  effects RBF/GFR  Cardiovascular baroreceptors  effects RBF/GFR o Humoral regulation:  Hormones for vasoconstriction: noradrenalin.Jan Kirchhof Physiology UMF Targu Mures Topic 29 Glomerular filtration. dopamine (!).

tubule (macula densa))  Cl delivery and reabsorbtion rate at macula densa changes JGA determines vascular volume change by change of: o Arterial pressure (direct + arterial barareceptors) o Venous volume (indirect through  atrial receptors (Vorhof)  sympathetic nerv. sign.. catecholamine (hormons)) o Fluid delivery to macula densa (direct) JGA response: o Renin release  changes rate of excretion: H2O + salt.g. dist. loop of Henle.Jan Kirchhof Physiology UMF Targu Mures Topic 30 Juxtoglomerular apparatus (JGA) – structure and function     JGA is situated near glomerulus and distal tubule (with macula densa) Equilibrium between GFR and tubular function  tubular function is adapted to maintain GFR constant o  tubularglomerular feedback mechanism (TGF) JGA regulates RBF/GFR through TGF If GFR changes (e. tubule. changes peripheral resistance o GFR change  changes rate of excretion: H2O + salt o Peritubular capillary pressure change (HP and π)  changes rate of excretion: H2O + salt   30 . high GFR  high tubular fluid flow rate  high Cl delivery) o  tubular fluid flow rate changes (through prox.

gluc. HCO3 of filtrate is reabsorbed H2O (60 – 70% of filtrate) is reabsorbed by osmosis. atropine. bases (acetylcholine. HCO2 formate. aminoacids. contact with interstitial fluid and blood vessels + major function: Na reabsorbtion (60 – 70% of filtrate) o at basolateral membrane: + +  primary engine: prim.g. gradient (neg. K in)  creates strong conc. oxalate) – antiport o At basolateral membrane:  Cl channel +  K -Cl symport Some weak organic acids (uric acid. K .): glucose. PAH. tubule Some substances (e. Cl . HCO3 ) + o e. out cell by independent mechanism  90% of glucose. act. gradient) 2+ 2+ +  sec. sodium glucose transport: 2 Na + 1 glucose  into cell. nutrients. Mg .Jan Kirchhof Physiology UMF Targu Mures Topic 31 Function of renal tubules Filtration o Large portion of plasma is filtered from blood into renal tubules  glomerular filtrate o Needed substances are put back into blood  reabsorbtion o Rest is left and excreted by urine  Reabsorbtion o Movement of H2O (passive) + solute (active or passive due to substance and tubular segment)  from tubular lumen into peritubular capillary network  Secretion o solute (mostly active) from blood into tubular lumen proximal renal tubules  constitution: o inner surface: luminal surface of epithelium  brush border of microvilli (increases surface)  role of epithelium: reabsorb ions. transport (conc. morphine)  actively secreted in prox. urea)  reabsorbed or secreted by prox.g. gradient)  symport (cotrans. tubule        31 . electrolytes (Ca . rest filtrate remains isotonic Bicarbonate reabsorbtion: + o At lumen: HCO3 (filtered) + H (secreted)  CO2 + H2O + o Inside cell: hydration of CO2 (CO2 + H2O)  H (goes to lumen) + HCO3 (transported to ISF by (1)Na-(3)HCO3 cotransporter) o  reabsorbtion of HCO3 (1 disappears from tubular fluid and appears at ISF) Chloride reabsorbtion: o At luminal surface: Cl-base(HCO3. penicillin). in cell) o at luminal surface: +  passive transport of Na (conc. active transport (ATP-ase: Na out. aminoacid. H2O  transport it to capillaries o outer surface: basal/lateral cell membrane  infoldings.

Cl from filtrate to surrounding medium (needs energy. almost completely impermeable to H2O +  Passive diffusion of Na . tubule  25% reaches loop of Henle + o 15 – 20% of original Na conc. little perm. in medulla) Reabsorbtion of H2O + solutes (flowed in medulla) by vasa recta (capillary network around loop of Henle in medulla) 75% of original glomerular filtrate reabsorbed by prox. presents 3 regions: o Thin walled descending limb  Highly permeable to H2O. maintains osm. reabsorbed by loop of Henle Tubular fluid (filtrate) leaves loop of Henle: slightly hypotonic (200 – 250 mOsm/l) to blood. Cl . contains mainly urea + wastes Interstitial fluid of medulla is hypertonic     32 . to urea. conc. Cl from filtrate to surrounding medium o Thick walled upper part ascending limb +  Active diffusion of Na . grad.Jan Kirchhof Physiology UMF Targu Mures Topic 32 Role of loop of Henle (in medulla)  Continuation of proximal renal tubule. almost completely impermeable to solutes  H2O from filtrate to surrounding medium by osmosis o π increases up to 1200 mOsm/l (at hairpin turn)  filtrate reaches isotonic state there o Thin walled lower part ascending limb +  Highly permeable to Na .

leaves at basolateral membrane by aquaporin3/4 Kidney is able to maintain osmolality of body fluids constant wide range of osmolar conc. cAMP. in blood. reabs. at dehydration + + + + o stimulates Na -K ATP-ase. 2 cell types  P(principal) cells +  Secrete K +  Reabsorb Na +   aldosterone released at low Na conc. high number of Na -. protein kinase A)  forces insertion of aquaporin2 at laminal surface/apical membrane  H2O moves (due to osmotic pressure) in cells.Jan Kirchhof Physiology UMF Targu Mures Topic 33 Role of distal tubule   Reabsorbtion of electrolytes and H2O (quantity due to hormonal control by aldosterone and ADH) Distal tubule can be divided (anatomically + functionally) in 2 parts: o Cortical collecting tubule (action of aldosterone). K -channels) o Renin angiotensin aldosterone system (active at hypovolemia. of K . of H ) o Medullary collecting tubule (action of ADH)  H2O leaves from filtrate to hypertonic medullary interstitium (H2O conservation. (50 – 1200 mOsm/l) excretion  33 . reduced diuresis (renal elimination))  ADH mechanism:  ADH attaches to V2 receptor o Starts cascade (Gs protein  adenylate cyclase. hypotension)  I(interrelated) cells + + + +  Acid-base regulation (by K -H ATP-ase pump  secr.

Cl o events (transport-.: H2O is reabsorbed  NaCl conc.to ingoing-air  no loss of energy at inner medulla: high urea concentration o loop of Henle  at thin descending limb l. decreases   34 .o. impermeability for H2O) o vasa recta (passive exchange)  going down towards papilla: taking urea from ISF  conc.o.H.H.o. of tubular fluid increases  at thin ascending limb l.H.: NaCl is reabsorbed (passive diffusion.Jan Kirchhof Physiology UMF Targu Mures Topic 34 Urinary concentration and dilution (bad topic)  due to osmolar gradient between corticomedullary junction and tip of papilla + + o reabsorbtion at thick ascending limb (l. K . permeability-related) at distal tubule and collecting duct explanation of osmolar gradient in medulla: countercurrent (Gegenstrom) multiplication theory o depends on countercurrent flow (example of an oven)  energy (heat) transferred from outgoing.)  Na . increases  going up from papilla: loss of urea into ISF  conc.

alkalosis: chloride depletion (Schwund).4. acidosis: accumulation of acid products (lactic acid. at brush border) o At distal tubule (10 – 20%) with carbonic anhydras (sit. Pco2 = 40 mmHg Kidney: 2 ways maintaining acid-base balance o Retaining filtered HCO3 + + + +  Reabsorbtion of HCO3 by H secretion (Na -H antiport. regulated mainly by lungs and kidney o blood buffers react to acids and bases (products of metabolism)  lungs: control independently CO2 excretion rate +  kidneys: control independently concentration of HCO3  excr. o dynamic process.o. HCO3  increased production of HCO3 and NH3  Met. acidosis: increased secretion of H  increased production of HCO3  Resp.Jan Kirchhof Physiology UMF Targu Mures Topic 35 Role of kidney in acid base balance  acid-base balance in various body fluids maintained by a constant H conc. anhydrase)  H2CO3 (dissociates)  H + HCO3  caused by plasma concentration.H.  Most excreted NH4 is secreted at collecting duct + o Nonionic diffusion of NH3  excretion of NH4  loss of H  generation of “new HCO3 “ o Disorders in acid-base balance  acidosis/alkalosis (can be compensated with HCO3 . 50% of excreted acid) o NH3 (ammonia) produced in tubular cells (end product of amino acid metabolism)  Glutamine (major precursor)   deaminated to glutamate (+GDH (glutamate dehydrogenase))  NH3  + PDG (phosphate dependent glutaminase)  NH3  Alinine. tubule  reabsorbed as NH4 at asc. diaretics   increased filtration + excretion of HCO3 +  35 .)   reabsorbtion of all filt. but not as fast as in lung CO2) +  Resp. alkalosis: decreased reabsorbtion + production of HCO3  Met.4) o Production is accomplished by phosphate buffer (HPO 4Na2/H2PO4Na)  leads to generate “new HCO3 ” (renews consumpted buffer base of fixed acid)  Secretion of ammonium – NH4 (ca.HCO3 ) in urine  VN: pH = 7. of acids (NH4 )/bases (H2PO4 . extracellular fluid volume o Excreting acid (regarding to non-volatile/fixed acid  50 – 100mmol/day)  Made by:  Formation and excretion of titratable acid (ca. vomiting. urea. etc.glutamine can be transformed to glutamate o NH3 can easily diffuse into tubular lumen and plasma (secretion)  Big portion secreted at prox. inside tubular cells) +  CO2 + H2O (with carb. 50% of excreted acid) o Amount of measurable excreted acid in urine (determine amount of base (OH ) bringing pH to 7. H ATPase electrogenic process) o At proximal tubule (80 – 90%) with carbonic anhydrase (sit. limb l. [HCO3 ] = 24 mmol/l.

metalazone): inhibit NaCl transport at distal tubule (do not use in renal problems) + o K sparing (sparen) diuretics: spironolacetone: autogonize (works against) aldosterone + amiloride: inhibits Na channels o Carbonic anhydrase inhibitors (acetazolamide): inhibit transport of HCO3 out of prox.o.6g + o Na 0. Cl transport at thick asc. tubule o Osmotic diuretics (manitol): is filtered.1% 2.6% 6. heart failure. not reabsorbed remains in lumen  creates osmotic pressure  pulls H2O from cell into lumen Urine composition (variable proportion of dissolved substances): o H2O 95% o Urea 2% 25.2g o Creatinine 0.2g o Uric acid 0. diuretics. o Thiazide diuretics (chlorothiazide.5g o Cl 0.18% o Phosphate 0.7g o HCO3 1.6% 3.12% 2+ o Mg 0.g.Jan Kirchhof Physiology UMF Targu Mures Topic 36 Dieresis.5liter/day) o Excessive accumulation of body fluids in some diseases (e.01% 2+ o Ca 0. tubule l. 1ml/min (1.03% 0.1g + o K 0.H.6g o NH3 0. composition of urine   Tubular fluid goes along nephron  enters ureter  enters bladder Diuresis (production of urine): approx. K .015%   36 . hypertension.05% o Sulphate 0. pulmonary and systemic edema)  Use of diuretics (“water pills”)  increase urinary salt + H2O excretion Diuretics (present several classes for specific sites of action in nephron) + + o Loop diuretics: inhibit Na .1% 4.

Jan Kirchhof Physiology UMF Targu Mures Topic 37 Renal failure. artificial kidney  Renal function disturbance (can lead to renal failure) due to: o Intrinsic conditions: infectious process. transfusion reactions Renal failure leads to temporary or permanent kidney damage o loss of normal function  can be substituted by artificial kidney  renal dialysis  substance transfer by semipermeable membrane (diffusion (small particles). 500ml/min)  requires good artery and vein. disturbance of blood supply o Extrinsic conditions: shock. toxic materials. can lead to permanent renal failure   37 . potentially reversible o Chronic renal failure: progress slowly over 3 month. osmosis)  one side: blood (velocity: 300ml/min)  other side: dialyzing solution (always fresh. lasts 4 – 5h. obstructive lesions. 3 times a week 2 types of renal failure o Acute renal failure: abrupt onset. hemorrhage (Blutung).

400ml) o urine comes from ureter  no reflux because valvular flaps at uretral-vesical junction initial accumulation  slightly increase in pressure (10 – 20cm .01 – 0.02bar) later accumulation  pressure increases slightly until capacity is reached at 200ml afferent (to CNS) impulses in pelvic nerves  sensation of distension (Spannung)  wish to urinate voluntary (freiwillig) control of micturition until 400ml o over 400ml pressure can increase to 100cm/0.1bar  involuntary micturition initiation of micturition: voluntary act  willful relaxation of external sphincter by inhibition of pudendal nerves (somatic) micturition reflex is autonomic: o activation of parasympathetic fibres  stimulation of detrusor muscle  increase in intravesical pressure (up to 25 – 50cm) o sympathetic hypogastric fibres  action not entirely clear (int. sphincter) 38 .Jan Kirchhof Physiology UMF Targu Mures Topic 38 Micturition (Urinieren)        urine is accumulated in vesica urinaria (capacity of approx. 0.

increase dieresis Important role in 1. PGF1A.25-dihydroxyvitamin D3 2+ o maintains Ca balance in body (by action of PTH (parathyroid hormone) 2+  increased Ca absorption (small intestine) 2+  increased Ca reabsorption (kidney)  increased bone mineralization    39 . meat)  Liver  25-dihydroxyvitamin D3 o Kidney  1. PGF2) and leukotriens: o Control RBF o PGs: induce vasodilatation.Jan Kirchhof Physiology UMF Targu Mures Topic 39 The role of the kidney as endocrine organ   kidney produces some hormones.25-(OH)2VitD3) production o Sunlight + 7-dehydrocholesterol   cholecalciterol (VitD3) (in small amount via diet  fish. PGI2. involved in endocrine regulation of body functions renin: o proteolytic (protein break down) enzyme o produced at level of JGA o induces activation of ANG1  forms ANG2  releases aldosterone EPO: o Controls erythropoiesis (look topic 12) Prostaglandins (PGE2.

Na reabsorption  40 . Mg + +  Increase elimination of Na . HCO3 o Kalicrein-bradykinin system  Induces vasodilatation  Opposing action of renin-ANG system o Renal prostaglandins (PGE2. K . PGF2)  Induce vasodilatation with diuresis and natriuresis o Thyroid hormones  Increase GFR o Insulin  Influences glucose transport o ACTH and glucocorticoids +  Increase glucose. PGF1A. increased Na reabsorption at prox.Jan Kirchhof Physiology UMF Targu Mures Topic 40 The neuro-humoral control of renal function  neural control of renal activity is limited (even normal function of transplanted kidney): o adrenergic stimulation (by sympathetic splachnic nerves) +   vasoconstriction (especially at afferent arteriole  reduced GFR. tubule) Humoral control of renal activity by several hormones: o ANG2  Via AT1 receptors (ANG2 receptor type 1)  vasoconstriction with reduced diuresis  Via AT2 receptors (ANG2 receptor type 2)  vasodilatation with enhanced diuresis and natriuresis o Aldosterone +  Enhances Na reabsorption o ADH  Induces massive reabsorption of H2O o PTH 2+ 2+  Reduces loss of Ca .

V: volume urin)  Creatinine (endogenous substance) filtered + 10% secreted (prox. P: conc. 0 – 250 mg/dl). > 250 mg/dl) 41 . of a substance according to the clearance depends on handling the substance by tubules  Handling: filtered clearance is constant  Handling: filtered + reabsorbed clearance increases  Handling: filtered + secreted clearance decreases o With clearance you can determine GFR  Inulin (fructose polymer) it is only filtered  GFR = (U*V)/P (U: conc. urin. ca.Jan Kirchhof Physiology UMF Targu Mures  Clearance: volume of plasma. 90%  represents volume of RPF o Glucose clearance:  Glycaemia <250 mg/dl 100% of filtrate is reabsorbed  Glycaemia 250 – 375 mg/dl reabsorbtion decreases  Glycaemia >375 mg/dl 0% of filtrate is reabsorbed  Glycaemia >250 mg /dl excretion in urine starts  Clearance: 0 (glyc. plasma. tubules) o With clearance you can determine RPF  PAH (p-aminohippuric acid (weak acid)) filtered + secreted (renal venous conc. 0)  Renal extraction of PAH ca. cleared from a given substance per time unit o The effect of increasing plasma conc. like inulin (glyc.

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