Introductory Physiology PSL 250
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Date Created: 09/19/15
L1 Introduction to PhysiologyLevels of OrganizationHomeostasis 5242012 103700 PM What is Physiology Functional anatomy Dynamic Processes o Maintaining or moving to a control set point Organization Each level built on the one below Molecules 0 Assembly of atoms 0 Major physiological ones are proteins carbohydrates lipids and nucleic acids Cells 0 The cell is the basic unit of life Uses energy has metabolism removes waste 0 Produce energy ATP 0 Metabolism carries out reactions Tissues 0 Collection of similar cells with some local function term also used generally such as lung tissue Organs 0 Collection of different tissues 0 Carries out distinct function in the body Systems 0 Collection of organs 0 Controls major coordinated functions Reparation circulation etc Homeostasis Maintain the normal physiological state What does your body try to maintain Every cell is surrounded by liquid Maintaining extracellular environment Internal Environment 0 o Negative feedback 0 Most commonly used 0 Event X causes a change away from state set point 0 Response y causes a return to set point Basis of homeostasis n Examples Blood pressure ion concentration muscle reflexes o Positive feed back 0 Rare but important 0 Event x causes a change to new set point state change 0 No return to original set point Examples Blood clotting part nurtition L2 Cell Structure Cytosol 5242012 103700 PM Liquid portion high content Protein clusters Organized enzyme pathways enhance metabolism Metabolism 0 Thousands of reactions 0 Enzymes are protein Catalysts 0 Structural proteins energy production Protein Synthesis 0 Chains of connected amino acids 0 Structure determined by genes 0 MRNA from nucleus codes for protein manufacture on ribosomes Ribosomes 0 Combination of protein and RNA 0 Free ribosomes make proteins for use in cytosol 0 Few or no modifications after production 0 Chaperones help protein folding Storage 0 Glycogen is polymer of glucose In skeletal muscle for use during contraction In liver to maintain blood glucose between meals a To supply brain with energy between meals Some in many other tissue Body stores sugar and turns into a little fructose and a lot of glucose Only thing brain uses for energy is glucose Endoplasmic Reticulum Complex network of interconnected membrane tubules Production of exported or organelle proteins Rough ER has ribosomes 0 Site of protein synthesis o Smooth ER 0 No ribosomes Fat membrane synthesis o Cholesterol prevents cells from popping o Too low of cholesterol increases chances of cancer o Too high of cholesterol increases chances of heart disease o Rough ER 0 Ribosome linked amino acids 0 Newly formed protein threaded into ER lumen as it is made 0 New proteins move through ER to smooth ER o Smooth ER 0 Produces vesicles that carry new protein to golgi Apparatus o Produces new membrane complex liquid molecules Golgi Apparatus o Series of flattened membrane tubes o Revives vesicles from SER o Site of protein modification o Directs vesicles with new protein to specific organelles on the cell membrane o Docking proteins on vesicles and destination membrane ensure proper delivery Protein Modification 0 Proteins in GA have amino acids removed or modified 0 Sugars are added to proteins and modified proteins only work in specific shapes 0 Most proteins naturally fold into their appropriate shape 0 Chaperones ensure that proteins fold properly o Exocytosis o Vesicles from GA with export proteins merge with embrane and dump contents Increase in intracellular Ca triggers exocytosis ATP needed Lysosomes o Known for endocytosis Contain digestive enzymes Merge with endocytotic vesicles Digest molecules down to usuable size 0 Proteins to amino acids 0 Complex Carbohydrates to monosaccharides Endocytosis 0 Must occur to balance exocytosis o Extracellular molecules bind reveptors and trigger membrane folding o Bateria or dead cells trigger phaygocytosis Peroxisomes 0 Many reactions 0 Contains antioxidatns Vitamin C and vitamin E also do this outside cells 0 Destroys oxygen raicals very reactive destroy protein functions L3 Energy Production Cytoskeleton ATP 5242012 103700 PM Adenosine Cellular money Anaerobic Energy Production Glycolysis O O O No oxygen involved In cytoplasm free atp and cell membrane ATP for Ion Pumps 2 ATPglucose without oxygen Only need membrane present Mitochondria Aerobic Energy Production 0 O O 0 Double membrane structure Out membrane has large pores TCA cycle inside matrix of inner membrane Electron Transport System part of the inner membrane uses oxygen Pryuvate gt mitochondria Citric Acid Cycle Krebs cycle TCA or citric acid cycle In mitochondrial matric 7 RXNs Mitochondrial Inner Membrane Cytochromes form electron transport system on inner membrane Oxidative Phosphorylation NADH donates electron to ETS H follows NAD recycled As e passes ATP made at 3 cytochromes E H Oxygen gt H20 use of inhaled oxygen 3 ATPNADH 2 ATPFADHZ 34 ATPglucose Vaults O Octagonal barrel shaped structures 0 May be involved in transport from the nucleus to the cytoplasm MRNA ribosomes are possible cargo o Cytoskeleton o Intracellular frameworks 0 Protein polymer filaments of different size and function 0 Microstubules Polymers of tubulin have and ends a Cell stabilitytransport along neurons moce vesicles organelles and chromosomes Movement n Kinesin carries cargo along microtubules in direction a Dynein moves cargo in direction towards nucleus n Taxol anticancer drug brinds to and stabilizes MTS kills dividing cells Cilia Flagella n Cilia o Lung oviducts dynein drives MT twist propels mucus ovum n Flagella o Propel sperm into ovum rotary movement Intermediate Filaments n Permanent load bearing filaments in stressed cells skin o Maintain shape Microfilaments n Thin filaments o Actin polymer n Thick filaments o Myosin polymer o Movements in muscle and WBC s L4 Membrane Structure 5242012 103700 PM Membrane Structure o Separates intracellular fluid ICF from interstitial fluid IF o Physical and chemical barrier o Phospholipids o Backbone of membrane 0 Soaplike o Fluidity within membrane and as a whole 0 Hydrophobichydrophilic Fat soluble center of membrane Hydrophobic molecules cross easily Hydrophilic outer sides of membrane a Hydrophilic doesn39t cross by diffusion except H20 a High water solubility due to small size o Cholesterol 0 Interspersed between lipid portions of phospholipids o Prevents close packing of fatty acid chains 0 Creates membrane fluidity flexibility o Proteins o In membranes 0 Some mobile some restricted o Channels 0 Only ions go through Protein channels span membrane Open or closed Specialized by ion type K Na Ca Cl 0 Receptors open channels 0 O O o Enzymes o Catalyze reaction A gt B 0 Some activated by receptors some always active o Receptors o On outside 0 Bind to solute either chemical Neurotransmitter hormone drug 0 Some activated by physical change Touch 0 Activated by either channel or enzyme o Dockingmarker Acceptors o Recognize and bind to secretary vesicles 0 Sites of exocytosis o Carriers o Revolving proteins no Anaphase 0 Alternate open side 0 2types 1 Molecules move with gradient 2 Cotransport with ion usually Na u use the ion gradient for energy Cell adhesions molecules o Anchor cells to other cells or to basil lamina noncellular surface o Maintain tissue integrity o Abnormalities occur during metastatic cancer o CarbohydrateProtein complexes 0 Identify self to the immune system 0 Basis for separation of cells into tissues during embryonic development 0 Limit normal tissue growth to confirmed region o Intracellular Connections 0 Proteins and large structures 0 CAMs Cell Adhesion Molecules Proteins Anchor cells Control cell migration 0 Tight junctions Block movement between cells Create tissue sidedness Skin intestines kidneys Allows selective transport molecules must go through cells 0 Desmosomes Need to live otherwise heart will tear itself apart Cellular rivets Hold moving cells together skin heart 0 Gap Junctions Channels between cells ions pass electrical link Electrical signal from one cell activates next cell a Heart gi tract L5 Membrane Transport 5242012 103700 PM Diffusion Across Membranes o Driven by chemical or electrical gradients 0 Simple diffusion channels and carriers 0 Diffusion goes in all directions Net diffusion will always go from high to low Hydrophobicity n Fats and gases cross easily a Fluidity allows 8 micron RBC s to deform through 7 micron capillaries enhances oxygen transport Size a Small objects pass through more easily than large objects 0 Fick s Law of Diffusion QPACXVW 0 Ion Channels Different types for different ions n NaKCaCl Allows ions to move by chemicalelectrical gradients o Osmosis The diffusion of water a Water moves from high water concentration to low water concentration a Semipermeable membranes allow water to cross but nothing else 0 Carrier transport Protein molecules change shape in membrane and move molecules across Energy for tansport may come from concentration grafient or from ATP Specificity a Each carrier transports a specific molecule or type of molecule Saturation n n i There are only a limited number of carrier in each cell When all carriers are being used the rate will be at a maximum The transport maximum TM limits carrier mediated transport Facilitated Diffusion n n a No ATP used moce down diffusion gradient Molecules bind to one side carrier reorients molecule leave on opposite side o More binding on high concentration side Movement from high to low concentration Active Transport 1 1 Use ATP for energy to move ions against from low to high concentration Ions move from high affinity side to low affinity side AT produces the ion gradients across all membranes o NaK ATPase 0 Moves Na out of cells moves K into cells 0 K is high inside cells Na is high outside cells 0 Creates gradient that allow electrical signaling 0 Ovabain blacks on NaK AT pose Secondary Active Transport o Carrier has 2 binding sites against ad Na o Energy of the Na gradient out to in drives SAT o Cotransport agonist in or counter transport agonist out Na transports some glucose and amino acids in this way 0 In some tissues other ions drive SAT Exam 3 L 21L31 L2 1 Cardiac Structure and Activation Cardiac Cell Structure Cylindrical shaped cells Intercalated disks join cells endtoend Filaments as in skeletal muscle Thin filaments activation by Ca binding to troponin Intercalated Disks Strong connection between cells Desmosomes for strength Gap junctions for electrical activation spread Circulatory Flow Circuit Systemic Left ventricle to aorta to body to vena cava to right atrium Valves maintain the direction of ow Cardiac Activation Structures Activation pathways has auto rhythmic cells Atria Site of normal heartbeat initiation SA Node In right atrium Depolarizes to threshold starts Action potential Fastest depolarization no stable baseline membrane potential The internodal pathway connects the SA node to the AV node Premature beats occur if the heartbeat starts elsewhere not usually harmful Atrial Muscle RIGHT atrium achieved by SA Node spreads toward the LEFT atrium using the internodal pathway Spread through gap junctions Not auto rhythmic contraction spreads downward AV Node Electrical connection from atria to ventricles Delays AP spread allows ventricular filling to be complete AV block produces separate atrial amp ventricular activation Ventricles AP enters septum first spreads to apex then up to ventricular muscle V muscles contraction spreads upwards Bundle of His Off ofAV node down the septum Purkinje Fibers Branch off septum to ventricular muscles Activated by bundle of His through gap junctions Ventricular Muscle Apex cells activated first by purkinje fibers Then muscle celltocell through gap junctions Contraction spreads upward forcing blood into aorta amp pulmonary artery No pacemaker activity Pacemaker Cells Auto rhythmic no stable baseline potential SA ampAV Nodes some cells of Bundle of His and Purkinje fibers Depolarization Na entry to threshold Opening of Ca channels during AP Opening of K channels during repolarization Little Na in uence on AP Neural In uences Sympathetic neuron s increase depolarization NE opens Ca channels in atria and ventricles Increases heart rate amp strength of contraction Parasympathetic neurons Vegas N Ach decreases depolarization rate Ach decrease Ca channel opening in Atria Decrease heart rate Electrocardiogram Sum of changes in cardiac action potentials Relation to Cardiac AP Detect changes in the sum of Aps 1st derivative sum of AP39s Changes in membrane potential detected by different distance to leads Ventricular fibrillation I Life threatening no coordinated emptying no blood delivery I Need electrical shock to recoordinate APs P Wave Atrial dep olarization Start of atrial contracting QRS Complex Ventricular depolarization masks atrial repolarization End of atrial contraction start of atrial filling Start of ventricular contraction T Wave Ventricular repolarization End of ventricular contraction start of ventricular filling L22 Cardiac Pumping Diastole relaxation amp filling Relaxed heart Time for filling End diastolic volume 130135mL Atrial Systole contraction amp emptying Contracts first then completes filling ofventricles Ventricular Systole contraction amp emptying Follows atrial contraction Contraction spreads UPWARD Pressure must be greater than aorta to open aortic valve Aortic Pressure Load the LEFT VENTRICLE works against High blood pressure puts a greater load on the heart Ejected Blood Volume 7090mL of blood ejected per beat 65 of end diastolic volume Lower heart rate means higher ejected volume Heart Rate Dependence Max heart rate is 220 age Rates above 180 decreases filling time but you must be highly motivated to exceed 180 Reaching 180 is dangerous because it decreases cardiac output Arterial Pulse Artery walls expand to hold blood Rebounds during diastole which is what creates a pulse Little drop in BP throughout arteries Heart Sounds Closing ofvalvesturbulent blood ow creates sounds Low pressure AV Mitral and tricuspid first then high pressure aortic amp pulmonary valves Different sound intensities Murmurs Nonsmooth ow sound when valves should be closed Valve Stenosis STIFF VALVE Does not open completely Turbulent ow as blood squirts through Blood must be forced through an opening at a tremendous velocity Results in whistle sound EXAM 4 L 32L4 1 L 32 Renal Filtration Reabsorption Renal Functions 0 Filter waste from blood 0 Maintain blood volume 0 Maintain blood osmolality how concentrated blood is 0 Uses filtration gets rid of everything reabsorption take the good stuff secretion Nephron 0 Functional unit of the kidney 0 Has vascular system amp tubular system 0 All by cells amp proteins in blood can be filtered 0 Most reabsorbed remainder urine Vascular System 0 2 capillary systems 1 for filtering 1 for reabsorption o Afferent arteriole 9 glomerulus filtration 9 efferent arteriole 9peritubular capillaries reabsorption 9venules Tubular System 0 S shaped o Bowman s capsule receives filtrate 9 proximal tubule 9 Loop of Henle 9 distal tubule 9 collecting duct 9 ureter 0 Variable reabsorption hormonal control ofvolume and osmolarity Glomerular Filtration 0 From glomerulus into bowmann s capsule o Glomerular capillaries have very wide pores 0 Only cells amp proteins not filtered Inulin o Fructose polymer Filtered not reabsorbed or secreted Used to measure glomerular filtration rate GFR Inject in blood measure in urine proportional to amount of filtrate GFR 125 mlmin 140 of total blood volume HydrostaticOsmotic Pressures o Hydrostatic pressure BP force into bowman s capsule o Osmotic pressures so much uid is filtered remaining proteins have higher than normal OP 0 Net lots of filtration Control of the GFR o Afferent arteriole radius controls entry to glomerules o Afferent arteriole dilation increases GFR o Afferent arteriole constriction decreases GFR o Sympathetic nervous constrict afferent arteriole decrease GFR Tubular Reabsorption 0 Must recover must filtrate o 125 filtered 124 mlmin reabsorbed 1 mlmin urine 9 14 Lday o 125 filtered 123 mlmin reabsorbed 2 mlmin urine 9 28 Lday 0 Excess urine loss in diabetes 9i Blood pressure 9 shock 9 death Transport Maximum 0 Different carriers for different molecules 0 Transport Maximum is limit of transport due to limited of carriers Glucosuria 0 3x more than normal carrier capacity filtered load 0 IfGlucosuria in urine blood must have at least 3x more glucosuria than normal Sodium Reabsorption 0 Controls reabsorption of many other molecules 0 Na pump only on basolateral side of tubular cells 0 ATP needed for energy 0 Tight junctions prevent ow in spaces bw cells 0 Caffeine decreases Na reabsorption Cotransport Carries Na amp cotransported molecule Glucose amino acids bicarbonate C1 are cotransported with Na during reabsorption Energy use is Na movement down gradient into cells H20 follows osmotically at proximal tubule Variable H20 reabsorption at distal tubule amp collecting duct Glucose Reabsorption o Binds to carrier with Na on luminal side to enter tubular cell 0 Separate nonNa glucose carrier moves glucose into interstitial space Proximal Tubule Water Reabsorption 0 6070 of water reabsorbed in proximal tubule o 180 L day filtered 1 L of urine variable 0 500ml of urine minimum per day to remove toxins o Osmotic reabsorption ofwater follows solutes especially Na L 33 renal Control Secretion filtrate Dilution ReninAngiotensin System 0 Maintain BP by T Na and H20 reabsorption o irenal BP 9 release of renin from kidney 1G cells 0 Renin is a protease I asezenzyme Production of angiotensin II o Renin converts angiotensinogen into angiotensin I o Angiotensin converting enzyme ACE converts Al to All 0 ACE is the walls of lung capillaries Effects ofAng II 0 Powerful vasoconstrictor 9 increase blood pressure 0 Causes release of aldosterone from adrenal cortex ACE Inhibitors 0 Block production ofAng II 0 Used as treatment for hypertension 0 Few side effects but may produce fetal development problems Tubular Secretions 0 Extra removal from plasma 0 Carriers and pumps move material from tubular cells into filtrate 0 Most secretions is at proximal tubule 0 Organic acids and bases secreted poisons medicines dyes food additives Renal Blood Flow PAH o PAH is totally secreted from plasma 0 Appearance in urine proportional to renal blood ow through kidneys o RBF 2025 of cardiac output H Secretion o Carbonic anhydrase in tubular cells makes H amp llCO3 o H secreted in both proximal amp distal tubules 0 Uses Na H counter transport H into filtrate o HCO3 9 interstitial uid net loss of ll K Secretion o K reabsorbed in exchange for Na in proximal tubule o The Na pump activity increases tubular cell K which increases its secretion by the proximal tubule cells 0 Since K and H both exchange with Na an increase in the secretion of one decreases secretion of the other Plasma Clearance Measure of the kidneys ability to remove a substance from the plasma It is the volume of plasma from which an amount of material has been removed Ifa substance is filtered out not secreted or reabsorbed like inulin its plasma clearance is the GFR If the substance is both filtered and secreted its clearance is greater GFR Ifa substance like PAH is filtered and entirely secreted its plasma clearance is the renal blood ow 2025 of CO Loop of Henle Creates osmotic gradient in kidney medulla 300 mOsm at cortex 1200 mOsm in deep medulla Filtrate at the end of the Loop ofHenle is 100 mOsm Plasma is 300 mOsm this is a perfect level Countercurrent Multiplication o Descending limb ofL ofH is H20 permeable o Ascending limb ofL of H is H20 impermeable H K Cl pumped out o Filtrate entering distal tubule always dilute 100 mOsm o Runners who overhydrate problems in potassium ion L 34 Urine Production Bladder Function Collecting Duct o Goes through from cortex to medulla 0 Always dilute filtrate at cortical end 0 Responds to vasopressin no VP 9 little water reabsorbed o Dilute urine Vasopressin 0 From posterior pituitary 0 Released when plasma osmolarity high 0 Causes insertion ofaquaporin s in Collecting Duct membrane Aquaporin s 0 H20 Vhannels H20 goes through aquaporins o Osmotic pressure of solute in medulla 260 mOsm draw water 0 Retain Diabetes Insipidus 0 Either decrease vasopressin production or lack ofkidney response bad receptor 0 Excess water loss 9 shock 9 death 0 Need to drink as much water to survive Urine Buffering o Filtrate PH must be 45 or greater for H to enter filtrate o Bicarbonate and phosphate from filtration and ammonia from tubular secretion buffer urine Aldosterone Effects 0 T ifactuve Na carriers on luminal side of collecting duct tubular cells 0 this increases Na reabsorption in collecting duct 0 H20 follows osmotically o K reabsorption is reciprocal to Na Secondary Hypertension 0 Reduced renal artery ow i renal BP 9 excess renin 99TBP 0 Treat with ACE inhibitors to block angiotensin 11 production 0 Diagnosis by determining RBF with PAH Renal Dysfunction 0 Wide glomerular pores 9 protein in urine 9 edema due to low protein 0 Loss of concentrationdiluting loss of nephrons multiple causes 0 Acidosis by eg lack of ammonia reduction H excretion 9i neural function Sodium Dysfunction 0 Excess Na retention leads to edema hypertension 0 ifiltering excessive aldosterone leads to heart failure Bladder Function 0 storage of urine 0 no changes after leaving kidney Ureter Entry 0 Ureter connects kidney to bladder o Ureters passes inside bladder wall at an angle 0 Increase bladder pressure closes ureters prevents back ow Bladder sphincters o Spinal re ex relaxation ofinternal sphincter when bladder pressure increases 0 Relax relaxation of external sphincter follows 0 Cortex can overcome relaxation of external sphincter o Parasympathetic neurons increase blood Control of Micturition o The ECF is the pool of available material for cells 0 Input comes from ingestion or metabolic production 0 Output occurs from excretion or consumption 0 Balance must occur the long run with input output L 35 Fluid Balance Balance Concept 0 The ECF is the pool of available material of cells 0 Input comes from ingestion ofmetabolic production 0 Must occur the long run with input output Negative Balance 0 Output is greater than input 0 Net reduction in pool concentration Positive Balance 0 Input us greater than output 0 Net increase in poor concentrations Fluid Balance 0 Balance of H20 in the body 0 60 of the body is H20 with adipose tissue 0 plasma 90 H20 soft tissue 7080 bone 22 and adipose 10 Intracellular uid 0 23 oftotalbody is H20 0 K dominated with protein Extracellular Fluid 0 13 of total body water 0 Na dominated Plasma o 20 ofECF w protein Interstitial Fluid 0 80 ofECF has no protein Minor ECF Components 0 Relatively small volume lymph CSF saliva etc ECF Volume Regulation 0 Regulation ofvolume needed for long term blood pressure control 0 Changes in blood pressure cause shift of uid between plasma and interstitial uid Blood Pressure Control 0 Short term A drop in pressure causes 0 Autotransfusion movement of uid from Interstitial uid to plasma to maintain blood pressure 0 Changes in baroreceptors activity 0 Long term control ofvolume is balance of thirstintake and kidney uid excretion Salt Intake 0 Kidney need 5g NaClday for uid loss in sweat o feces intake is 105g NaClday 0 Excess is secreted in urine 0 Cl follows Na Salt Excretion o Kidneys good at eliminating Na but increase retention increases blood pressure 0 Must balance 105g 1 day input 0 Fitness reduces Na content in sweat ReninAngiotensinAldosterone System 0 Long term control ofNa excretion controls BP 0 Everyone has their own set point for blood pressure ECF Osmolarity Control 0 Needed to prevent swelling or shrinking of cells 0 Total amount of material in volume regardless of composition production its osmolarity Ions Na and K dominate the osmolarity of Intercellular uid and interstitial uid Other nonpenetrating substances like proteins also contribute to its osmolarity Normal ICF and IF osmolarity is 300 mOsm Tonicity o The stand for tonicity is not the number of dissolved particles but the behavior of the particles in the solution Cells swell in hypotonic solutions ECF is rarely hypotonic Hypertonicity 0 Cells shrinkin hypertonic solutions gt300 mOsm o Dehydration low intake excess loss in diabetes Vasopressin 0 Controls osmolarity of urine 0 VP adds aquaporins to collecting duct increase water reabsorption Water intake 0 Fluid drinking food intake metabolism adds H20 0 Balance H20 loss from lungs sweat skin feces amp urine Osmoreceptors o Receptors in hypothalamus that control VP release 0 Increase osmolarity increase VP release ampwater retention 0 Decrease osmolarity VP release and increase water eXtention L36 AcidBase Balance Acid 0 Acids are AH acids dissociate into A and H 0 Strong acids like HCl in the stomach completely dissociate 0 Weak acids like H2CO3 carbonic acid partially dissociate Bases o Bases B can bind to become BH o The only significant physiological base is ammonia NH3 becomes NH4 0 Ammonia buffers renal filtrate allowing more H excretion pH 0 Measures ofH in a solution 0 pH long H increases in H cause decrease in pH 0 The average blood pH is 74l average cell pH is about 70 0 Blood pH below 735 is acidosis blood pH above 745 id alkalosis o Acidosis is far more common than alkalosis 0 Cells will have bigger pH shifts than blood Acidosis Effects 0 Acidosis depresses the neurons especially in the CNS 0 Alkalosis makes neurons hyperexcitable o Acidosis in general decreases enzyme activity but a few increase 0 Acidosis causes increase H excertion amp therefore decreased K excretion increased K causes cardiac amp neural problems Source of H 0 Small amounts in food such as citric acid 0 Most generated in the body carbonic acid from C02 sulfur and phosphoric acids from proteins metabolic acids such as lactic acid Control of H o H is controlled in three ways 1 Chemical buffering 2 Respiratory control of C02 3 Renal control ofH excretion Buffers 0 Different buffers work in different places 0 Buffers work by binding H converting A into AH o This removes H from the solution and from pH 0 First line of H defense Extracellular Buffering o Bicarbonate is the most important ECF buffer 0 HC02 bind H to form H2CO3 which dissociates to C02 and H20 0 Hemoglobin in RBC s buffers H produced by C02 increases in venous blood Intracellular Buffering 0 Proteins in cells bind H in ICF o In some cells especially muscle cells phosphate helps buffer ICF Urine Buffering o Phosphate and bicarbonate are dissociated acids that buffer renal filtrate o Ammonia is a base that also buffers renal filtrate Respiratory Control of H 0 Second line of H defense works with nonrespiratory sources of H 0 Increased H or increased C02 increases depth and frequency ofrespiration o This reduces C02 in blood reducing H back toward normal Kidney Control of H 0 Third line of H defense 0 Removes H from any nonrenal source in the body H Excretion o H ion pumps in the renal tubules secrete H into the filtrate o Urine pH is normally 60 but can be as low as 45 AcidBase Imbalances 0 Pathological changes in the control of H result in pH changes 0 These can be compensated by respiratory and renal systems ifnot of respiratory or renal origin 0 A system cannot compensate for its own problem renal problems require respiratory compensation respiratory problems require renal compensation Respiratory acidosis o Abnormal C02 retention from hypoventilation 0 Lung disease drugs nervemuscle disorders breath holding 0 Renal compensation by increase H secretion 0 Overdose of opiates drugs Respiratory Alkalosis o Decreased C02 by hyperventilation o Fearanxiety aspirin poisoning conscious breathing o Decreased H secretion or removal of condition Metabolic Acidosis Most common acidbase disorder 0 Severe diarrhea loss of bicarbonate 0 Excess H production during fat use in diabetics 0 Exercise leading to lactate amp H production 0 Kidney failure cannot excrete H or conserve HCO3 Metabolic Alkalosis o Decreased in H for nonrespiratory reasons Vomiting loses H in vomitus Excess bicarbonate ingestion Decrease respiratory rate and retain H in kidneys to compensate O O O o H retention increases K Loss L 37 Cardiovascular Regulation Hypertension Local Control 0 Nonneural factors 0 Decrease P 9 Decrease Flow 9 homeostatic tissue response 9 Increase ow 0 Auto regulation each organ controls local blood ow Metabolic Vasodilators 0 Active tissues produce vasodilators 0 ATP use 9 increase adenosine production 0 Adenosine is a strong vasodilation active hypertension Endothelial Factors 0 Paracrines 0 Released from endothelium affect Vascular Smooth Muscle Nitric Oxide 0 Hormonal neural activation 0 Increase NO 9 relaxes Vascular Smooth Muscle 9 increase blood ow Endothelin o Peptide 9 constricts Vascular Smooth Muscle o Decrease ow 9 increase blood pressure 0 Stimulates of endothelin increase gene activity that make SE Baroreceptors 0 Stretch receptors in carotid sinus and aortic arch 0 Changes in BP after baroreceptor activity Input to Medulla o Baroreceptors send neurons to medulla in brainstem Control ofVasoconstrictionDilation 0 Cardiovascular control center CCC in medulla 0 CCC controls sympathetic and parasympathetic output 0 Homeostatic short term control ofBP o Sympathetic decrease BP9 increase baroreceptor input 9inc sympathetic output 9 increase BP heart rate amp Vascular Smooth Muscle o Parasympathetic increase BP 9 baroreceptor input 9 increase parasympathetic output 9inc BP lower HR Resetting Body adjusts to own quotnormalquot BP 0 Adaptation to prolonged BP change occurs over days Hypertension 0 Chronic elevated BP 0 Multiple causes several small changes cause increase BP Cardiac Effects 0 Hypertrophy against increased load diastolic pressure 0 Increased oxygen use heart attack when coronaries constrict 0 With age increases in systolic pressure increase stroke age Essential hypertension 0 Causes unknown we treat symptoms 0 Effective reduces pathology Renal Hypertension Decrease blood ow to kidneys cause increase kidney renin release Renin converts angiotensinogen to Angiotensin I AI Angiotensin converting enzyme ACE in lung capillaries coverts Al to Angiotensin II Angiotensin II increases BP strong vasoconstrictor and causes aldosterone release from adrenal cortex Aldosterone increase Na reabsorption and H20 reabsorption by kidneys more volume In pregnancy 0 Placental factor causes vasoconstriction o Preeclampsia is hypertension during pregnancy Drug Treatments 0 Often used in combination 0 Varying side effects Diuretics 0 Increase Na excretion lowers blood volume decrease BP ACE Inhibitors Blocks the conversion ofAngiotensin I 9 II aAdrenergic Receptor Blockers o Stops sympathetic constriction of VSM blocks NE effects 0 Fewer Ca channels open less Ca entry less force 3 Adrenergic Receptor Blockers 0 Blocks NE EPi effects on the heart less Ca entry 0 Decreases force of cardiac contractions 0 2m1 to last resort Calcium Channel Blockers o Decreases VSM contraction clocks tone 0 Almost impossible to control BP then this is used Shock 0 Very low BP 0 Loss ofblood toxic vasodilation o Reversible shock can recover from o Epinephrine increases BP side effects significant 0 Irreversible shock multiple organ failure due to low BP 0 Death results only difference between the two L 38 Digestion and Absorption Carbohydrate Digestion 0 Must be reduced to monosaccharides to be absorbed Complex Carbohydrates o Chains of sugars usually glucose Different complex carbs have different links between sugars Starch is different than cellulose we cannot digest Sugar in fruit is often monosaccharide fructose or glucose Enzymes o Produced in the mouth amp in the pancreas Amylase converts starch to disaccharides Disaccharidases are in wall of the small intestine Disaccharidases convert disaccharides to monosaccharides Sucrose is converted to glucose Lactose Intolerance o Lactose is milk sugar disac of glucose ampgalactose o If no lactose is produced no digestion of lactose o Bacteria in large intestine use lactose as food source 0 Gas and diarrhea produced Absorption 0 Complete all sugars totally absorbed o No diffusion use glucose transporters Sodium dependence Glucose cotransported with Na into epithelial cells 0 Transport of glucose from epithelial cells to interstitial uid uses a nonNa glucose transporter Protein Digestion 0 Some in stomach most in small intestine Proenzymes Released in protected form Acid then pepsin converts pepsinogen into pepsin Enterokinase stomach enzyme in SI wall converts trysinogen into trysin Trysin then converts other pancreatic proteases into active form Peptidases 0 Both from pancreas and on small intestine wall 0 Convert peptides into amino acids 0 Some di and tri peptides absorbed Absorption ofprotein 0 Use amino acids transporters in mucosal wall 0 Some use Na C1 or no cotransporter Sources of protein 0 50 food 25 digested enzymes 0 25 mucosal cells 0 no dietary protein in feces Infant protein absorption 0 newborn can absorb protein directly until tight junctions form o igG in colostrum provides protection Lipid Digestion o mouth and stomach lipases unimportant o pancreatic lipases enter duodenum in ACTIVE form Lipases o Lipases convert triglycerides into monoglycerides and free fatty acids 0 Covert lipids to absorbable form Micelles o Bile salts from liver emulsify MG amp FFA amp cholesterol 0 Fats diffuse into mucosa at brush border Absorption Mg and FFA cross and reforms into TC in mucosal cells TG and cholesterol form chylomicrons Chylomicrons enter lymph through thoracic duct to blood Portal Vein o Carries water soluble foods directly to liver 0 Liver processes and detoxifies foods 0 Fats 9 lymph 9 blood9 everywhere 9 liver Electrolyte Absorption Salt all H20 soluable gt portal vein SI had tight junctions Salts use carries channels and pumps to go through cells Water 0 2000 mlday ingestion 7000 mlday secretions o 200 mlday in stool o Follows other absorption osmotically Sodium Most Na enters through cells energy gradient from Na pumps on basolateral side of mucosa as in kidney Some Na entry through leaky tight junctions Potassium K enters down concentration gradient through channels K exchanged from Na last electrolyte absorbed During diarrhea K loss to fast for reabsorption Active transport of K in COLON Bicarbonate Huge secretion by pancreas buffers acids in duodenum Reabsorbed by concentration gradient in SI Vitamins Watersoluble B ampC vitamins rapidly absorbed rapid loss of urine Must take in B ampC daily BlZ absorption needs intrinsic factor from stomach Vitamins A D E Kfat soluble gt micelles gt lymph Minerals 0 Ca 3080 absorbed Vit D dependent o Ca binding proteins ampCa ATPase increase Ca entry L 39 GI Intro Mouth Esophagus GI Layers Mucosa epithelial cells Submucosa longitudinal muscle submucosal plexus Muscularis circular and longitudinal smooth muscle myenteric plexus Serosa outer epithelial layer produces serosal uid GI Innervation Plexuses neurons control local contractions Longitudinal muscles propulsion of chyme Circular Muscles mixing food and secretions Parasympathetic Neurons o Activate plexus 9 increase Gi activity 0 Sympathetic neurons decrease GI activity Basic Electrical Rhythm Variable electrical baseline Ca2 and K channels open close Contraction when BER reaches threshold and APs occur Migrating Motility Complex Storage contraction migrates from stomach to end of SI Starts as previous meal nears complete digestion Clears stomach and SI in anticipation of next meal GI Hormones Released in different areas Both upstream and downstream effects Gastrin From stomach protein strongest stimulus for release Increase stomach secretion ofacid and pepsinogen Increase SI ilocecal valve relaxation 9empties SI Initiate mass movement in LI that triggers defecation Cholecystokinin CCK Secreted by duodenum into blood when fat or protein present Cause contraction of gall bladder Cause release of pancreatic digestive enzyme Inhibits stomach secretions Secretin o Secreted from duodenum into blood when H in duodenum 0 Increase secretion of pancreatic bicarbonate into pancreatic duct 0 Bicarbonate neutralizes stomach acid in duodenum Mouth 0 Little digestion here 0 Almost no absorption only some medicine 0 Nitroglycerin absorbed by oral mucosa Secretions o Bicarbonate neutralizes acids 0 H20 amylase lipase mucus to coat food 0 Lysozyme antibacterial enzyme Swallowing deglution o Boluses formed coated with mucus 0 Voluntary propulsion to pharynx o Re ex relaxation of upper esophageal sphincters Esophagus 0 Tube to stomach sphincter at each end 0 59 seconds transit time to stomach o no digestion or absorption Sphincters Upper esophagus sphincter relaxes upon swallowing Peristaltic contractions behind bolus force it into stomach Lower esophagus sphincter normally tightly closed relaxes to let bolus in Re ux 0 Acid into esophagus through LES 0 Loss ofneural input most common cause 0 Acid irritates esophagus hear burn potential ulcer Gas 0 In stomach o Swallowing gas some burped out some absorbed some to colon 0 Most colonic gas is bacterial L 41 Stomach Pancreas Liver Stomach 0 Holds contents kills pathogens starts protein digestion o Relaxes as food enters hold up to 1 liter Structure 0 Lining has gastric pits cells produce secretions o Mucus coats gastric pits prevents HCl killing cells Secretions o Pepsinogen o HCl separate H and Cl pumps pH 12 0 Mucus gastrin intrinsic factor for 812 absorption Motility o Peristaltic wave 3 min fundus to body to antrum o Forces food into antrum crushes blouses there forms chyme o Chyme is a mixture of food and secretions Emptying Pyloric sphincter separates antrum and duodenum Pyloric sphincter squeezes shut as boluses are crushed Only a small amount of Chyme squirts through Ulcers 0 Open sores in stomach cells exposed to acid 0 Kills cells no mucus covering Histamine is released Acid gt damage gt histamine gt more acids Positive feedback loop Treatment stop acid secretions neutralize acids H Pylori Bacteria 0 Live in gastric pits o gt 50 of all ulcers 0 hard to get to due to mucus antibiotics can kill H Pylori Exocrine Pancreas Secretes bicarbonate solution to neutralize stomach acid Secretes enzymes for digestion Duct System 0 Carries solution to duodenum o Duct cells secrete bicarbonate solution Alkaline Secretion Bicarbonate solution Pancreatic Aqueous Alkaline Solution PAAS Almost entirely Na Bicarbonate 45 X more bicarbonate than plasma 15 Lday or more Regulation Increased H lower pH in duodenum cause secretion release into the blood Secretion from duodenum causes releases ofNa Bicarbonate solution 9 PAAS Enzymatic secretions Proteases released in protected form Lipase and amylase released inactive form Pancreas has trypsin inhibitor for protection Regulation Fat or protein in the duodenum causes CCK release CCK causes acinar cells to release Enzymes carried to duodenum by DAA39s Parasympathetic neurons increase enzymes release sighsmell response Liver Releases bile into duodenum to emulsify fats Mostly undifferentiated cells 100039s of metabolic reactions Makes plasma proteins Blood Supply 2 sources merge liver sinusoids Hepatic artery supplies oxygenated blood from heart Portal vein carries water soluble foods from S1 Bile Salts Major component for bile made by hepatocytes Released into bile canaliculi on opposite side from blood Bile salts form micelles 9095 ofbile salts reabsorbed at ileumrecycled Bilirubin Metabolism Formed from heme oflysed RBC39s fat soluble circulate bound to albumin Released to liver cells gt modified to H20 soluble form gt most to bile gt feces Some is absorbed at the ileum excreted in urine Provided color for both urine and feces Iaundice is a build up of Bilirubin usually liver problem Gall Bladder Funtion 0 Stores bile between means when sphincter of oddi closed 0 CCK relaxes S of O and contracts the GB 9 bile enters duodenum Gallstones Calcium bilirubinate some or cholesterol stones most Form in gall bladder w glycoprotein binding Can block S of O gall bladder binding If gall bladder removed bile duct expands to hold bile L 41 Small Intestine Large Intestine Small intestine 0 Primary site of digestion and absorption Structure 0 Deuodenum jejunum ileum 0 Many folds increase surface area 600 folds o 9 Lday presented 2 food 7 secretions o 12 Lday to colon 200 mL in feces Villi Folds of SI wall tissue Crypts of Lieberkuhn base Cells migrate upward die by digestion Cells replaced every 3 days Microvilli brush border 0 Fold of cell membrane at the tips ofvilli cells 0 Site of absorption 0 Bound enzymes on surface enterkinase Disaccharidases etc Mucus secreted w H20 Contains glycoproteins covers SI epithelium in C of L and upwards Protection from digestive enzymes Motility Basic Electrical Rhythm BER higher at duodenum than at ileum Moves chyme down SI peristaltic waves oflongitudinal smooth muscle Segmentation miXing contraction of circular smooth muscle Malabsorption Decrease Amino Acids absorbency 9wasting decrease muscle mass Decrease carbs and fat absorbency 9 increase stool and gas and decrease vitamin absorbency Autoimmune Crohn39s and allergic gluten enteropathy disease Diarrhea 0 Multiple cause most common SI motility gt absorption 0 Loss of H20 and K potentially serious or fatal neuralheart problems 0 Dehydration leads to shock 0 Travel change in waterelectrolytes kill bacteria or E Coli other bacteria in food Large Intestine Colon Handles absorption ofHZO and Na as well as some K No nutrient except some from bacteria Structure SI 9cecum 9 descending transverse descending colons 9 rectum 9 anus Internal and external sphincters control anus Appendix closed pouch oflymphoid tissue off cecum Gastrioileal Re ex Food in stomach cause relaxation of cecum and allows ileum to empty Gastrin relaxes ileocecal valve Absorption 0 Active transport of Na water follows Feces Fiber Feces is minerals fiber bacteria H20 Bacteria grow even during starvation Fiber is cellulose and related compounds Fiber increases colonic activity decrease colon Bacteria E Coli and the other types appear soon after birth Bacteria require nutrients from the colon mucosa May produce useful vitamins and essential Amino Acids Can invade body after radiation poisoning Defecation Gastrin triggers colonic9 most movement into rectum increase pressure Increase rectal pressure causes re ex relaxation ofinternal anal sphincter smooth re ex Voluntary control of external anal sphincter skeletal muscle Constipation Defecation caries from 3day to 13 days No significant health consequences except discomfort No 39poison39 absorption Flatus Most is bacterial some from ingestion Multiple smells due to sulfides Sound force through external sphincter Basal Flatal Rate 15 mLhr 1 passagehr Lecture 1 Introduction to Physiology Levels of Organization Homeostasis 1 Whatis physiology a Functionalanatomy i The body changes overtime 1 Growth is slow movement of the limbs is quick ii They change is a way that allows you to maintain a particular set point 1 Controlled by negative feedback 2 People don39t die of old age the die of inability to maintain a set point 3 Can39t live forever until we figure out a way to maintain the kidneys 2 Organization a Each level is built on the one below b Each level had characteristics that the lower one doe now i Molecules 1 Assembly of atoms 2 Major physiological ones are proteins carbohydrates lipids and nucleic acid ii Cells 1 The cell is the basic unit of life 2 Uses energymuse metabolismremoves waster 3 Two types of cells Muscles and neurons are incapable of reproduction iii Tissues 1 Collection of similar cells with the same local function a Skin cells muscle cells etc 2 Term also used generally such as lung tissue iv Organs 1 Collection of different tissues 2 Carries out distinct function in the body v Systems 1 Collections of organs 2 Controls major quot 39 functions I 39 39 quot etc 3 Homeostasis a Maintains the normal physiological state b Internal environment i 0 Interstitial fluid 1 4xs more than blood 2 Liquid around cells Body will do things to make you maintain your normal functioning state d Negative Feedback i ii iii Ex High blood pressure muscle reflexes When event X causes a change away from a set point and then response Y causes it to return to the set point Basis of homeostasis 1 Fall in blood pressure activates sympathetic nervous system e Positive Feedback i Event X causes a change from out set point to another Rare but important iii Ex Blood clot pregnancy Lecture 2 Cell Structure 1 Cytosol a Liquid portion high protein content V V i Originally called cytoplasm b Protein clusters organized enzyme pathways enhance metabolism c Metabolism i Thousands of reactions ii Enzymes are protein catalysts iii Structural proteins 1 Create the nonspherical shape of the cells iv Energy production enzymes v storage and use of carbohydrates and lipids d Protein Synthesis i Chins of connected amino acids ii Amino acids only need 20 to make all of the proteins In the body 1 8 cannot be produced and must be consumed in your diet iii Structure determined by genes iv mRNA travels from nucleus codes for protein manufacture on ribosomes e Ribosomes i Combinations of protein and RNA ii ribosomes make proteins for use in cytosol iii Few or no modifications after production iv Chaperones help protein folding f Storage i Glycogen is the polymer of glucose sugar 1 In muscle for use during contraction 2 In liver to maintain blood glucose between meals a Between meals the glucose is broken down and used for blood glucose for the brain 3 Some in many other tissues Endoplasmic Reticulum a Complex interconnected membrane tubules b Smooth and rough are all part of one system c Smooth ER i Smooth ER manufactures membrane and fat has no ribosomes ii produces vesicles that carry new protein to Golgi apparatus d Rough ER i Rough ER manufactures proteins Has ribosomes i39 ribosomes link amino acids iii Newly formed protein threaded into ER lumen as it is made 1 Lumen Inside part in this case of the ER iv New proteins more through ER to smooth ER Golgi Apparatus a Series of flattened membrane tubules site of protein b Receives vesicles from Smooth Endoplasmic Reticulum c Directs vesicles with new protein to specific organelles or the cell membrane d Docking proteins on vesicles and destination membrane ensure proper delivery e Protein Modi cation i Proteins in the Golgi Apparatus have amino acids removed or modified ii Sugars are added to proteins and modified 1 Sugars on surface of cell added in specific patterns that tell body to not attack itself iii Proteins only work in specific shapes remember the treble cleft 1 Most proteins naturally fold into their appropriate shape 2 Chaperones ensure that proteins fold properly a If they don39t there is a distinct evolutionary disadvantage f Exocytosis i Vesicles from Golgi Apparatus with export proteins merge with membrane and dump content quotquot and are 39 39 into ii Intracellular Ca triggers Exocytosis ATP needed iii Adds membrane to the cell but because of homeostasis stay the same lysosomes need to take back some of the membrane from the cell 4 Lysosomes a Contain digestive enzymes merge with endocytotic vesicles to digest molecules down to usable size b Proteins to amino acids c Complex carbohydrates to monosaccharides single ring d Endocytosis i Must occur to balance exocytosis extracellular molecules bind receptors and trigger membrane infolding ii Pinocytosis cell drinking replaced by endocytosis e Peroxisomes i Many reactions contains antioxidants Vitamin C and E and destroys oxygen radicals very reactive destroy protein function ii Water is the most common substance In your body 1 Radiation for cancer treatment is most likely to react with water iii Hydrogen peroxide can kill almost any cell 1 You don39t hear about internal hydrogen peroxide poisoning because of catalase in your body reacts so fast f Phagocytosis i A cellular defense mechanism ii Enclose a whole dead cell or bacteria cell iii White blood cells will sacrifice themselves while fighting infection iv Pus is dead bacteria and dead which blood cells Lecture 3 Energy Production 8d the Cytoskeleton 1 ATP Adenosine PPP a Cellular money b X ATP gt xp ADP 2 Anaerobic Energy Production Glycolysis a In cytoplasm free ATP and cell membrane ATP for ion pumps i 2 ATPglucose without oxygen b Glucose NAD ZADP 9 9 reactions 9 NADH 2 Pyruvate c NADH pyruvate 9 NAD lactate recycle NAD 2 ATP 3 Mitochondria aerobic energy production a Double membrane structure b Outer membrane has large pores to let things in and out c TCA cycle citric acid cycle Krebs cycle inside matrix of inner membrane d Electron transport system part of the inner membrane uses oxygen e Pyruvate mitochondria f Citric Acid CycleKrebs CycleTCA i In mitochondrial matrix there are seven reactions ii fats enter at the AcetylCoA step 1 Carbons come in even numbers and are split off two at a time to become AcetylCoA g Mitochondrial Inner Membrane i Cytochromes form electron transport system on inner membrane h Oxidative phosphorylation i NADH domestics electrons to the Electron transport system ETS H follows NAD recycled ii As e passes H pumped at three cytochromes ATP made on H return iii E plus H plus oxygen equals h20 use of inhaled oxygen iv 253 ATPNADH 15 ATPfath 30 ATPglucose v Anaerobic system 1 No oxygen only get 2 ATP vi Aerobic system 1 Krebs cycle and get 30 ATP carbon dioxide and water 4 Vaults 3 b Octagonal barrel shaped structures that may be in involved in the transport from the nucleus to the cytoplasm mRNA and ribosomes are possible cargo 5 Cytoskeleton 3 b n V Intracellular frameworks protein polymer filaments of different sizes and functions Microtubule i Polymers of tubules have and ends nothing travels down the center the action is on the outside i39 Cell stabilitytransport along neurons move vesicles organelles and chromosomes Act as a pipe that holds the integrity of the long cells together Glucose takes 63 years to travel from the brain stem to the end of your big toe Movement 1 Kinesim carries cargo along microtubules in a positive direction toward the membrane 2 Dyne in moves the cargo in a negative direction away from the membrane 3 Taxol anticancer drug binds to and stabilizes MTs kills diving cells Cilia In the lungs sweeps debris towards mouth which is usually swallowed 1 Also in the oviduct Fallopian tubes vii Flagella Propel sperm cells into ovum rotary movement Intermediate Filaments i Permanent load bearing filaments in stressed cells such as skin ii Maintains shape Micro lament i Thin filaments actin polymer ii Thick filaments myosin polymer iii Movements in muscle and WBC iv Keratin an intermediate filament 53 S Lecture 4 Membrane Structure 1 Membrane Structure 3 b c D V m V Separates intracellular fluid ICF from Interstitial fluid IF Physical and chemical barrier Phospholipids i Backbone of membranes soap like ii Fluidity within membrane and as a whole iii Cholesterol holds membrane from quotpoppingquot 1 Without cholesterol it would pop like a soap bubble iv HydrophobicHydrophilic 1 Fat soluble center of the membrane 2 Hydrophobic molecules cross easily 3 Hydrophilic outer sides of the membrane a Hydrophilic don39t cross by diffusion excel h20 b High water solubility due to small size i Water can cross the membranes between lipids Cholesterol i Interspersed between lipid portions of phospholipids ii Prevents close packing of fatty acid chains iii Create membrane fluidity flexibility Proteins i Imbedded in membranes some are mobile and some are restricted ii Receptors 1 on outside bind to solute either chemical neurotransmitter hormone drug or ion v V 2 Some are activated by physical change a Sound light touch b fa ball hit you in the eye and you said you saw quotstarsquot receptors activated by pressure instead of light causing a light flash i There aren39t really stars but your brain produces an image because that is the normal thing to do 3 Activate either enzyme or channel iii Channel 1 Only ions go through channel is specific for given ion 2 Protein channels span membrane 3 Open or closed 4 Specialized ion type k Na Ca Cl 5 Receptors open channels nzymes 1 Catalyze reaction A 9 B some are activated by receptors some are always active 2 Regulated by receptors 3 Some are on the outside of your cell v DockingMarker Acceptors 1 Recognize and bind to secretory vesicles 2 Site of exocytosis Carriers 1 Revolving proteins no ATPase 2 Alternate open side 3 Two types a Molecules more with gradient b Cotransport with ion usually Na use the ion gradient for energy source CarbohydrateProtein complexes i Identify you to the immune system ii Basis for separation of cells into tissues during embryonic development iii Limit normal tissue growth to confined region E V mAAAA V Intercellular Connections 352 D V m V v V All cells have negative outsides No cells actually touch but are tethered CAMs Cell Adhesion Molecules i Proteins that anchor cells to other cells or to basal lamina noncellular surfaces ii Maintain tissue integrity iii Abnormalities occur during metastatic cancer iv Control cell migration TightJunctions i Clock movements between cells ii Create tissue sides iii Skin intestines kidneys iv Allow selective transport molecules must go through cells v Prevents fluids from leaving the skin 1 Wrinkling of fingers in water means that water has moved across the skin Desmosomes i Cellular rivets ii Holds moving cells together skin heart 1 Being born means that you don39t have a genetic deficit in your heart because of you had a problem with your Desmosomes you would never make it past your first heart beat during gestation the heart would rip itself apart Gap Junctions i Channels between cells ions pass electrical link ii Electrical signal from one cell activated next cell 1 Current sent through heart to recoordinate heart cells not restart 2 During contractions the entire uterus contracts as one 3 Present in any cavity you have that empties out iii Heart GI tract bladder uterus Lecture 5 Membrane Transport 1 Diffusion Across Membranes N V U a Driven by chemical or electrical gradients b Simple diffusion channels and carriers c Diffusion goes in all direction d Net diffusion will always go from high to low e ND diffusion from A to B diffusion from B to A f Hydrophobicity i Fats and gasses can cross easily fluidity allows 8 micron RCBs to deform through 7 micron capillaries enhance oxygen transport ii Average blood cell is 8 microns wide g Size i Small objects can pass through more easily than large objects h Ion channels i Different types of channels for different types of ions 1 Na K Ca CI ii Allows ions to move by chemicalelectrical gradients Osmosis a The diffusion of water water moves from a high concentration low solute concentration to a low concentration high solute concentration b Semipermeable membrane allow water to cross but nothing else c Water is really the only thing that moves across membranes Carrier transport Protein molecules change shape on membrane and love molecules across I b Energy for transport may come from concentration gradient or ATP c all monosaccharides can be moved by glucose carriers but at different rates d Speci city i Each carrier cam transport a specific molecule or type of molecule ii quotFamilyquot of molecules with a similar structure e Saturation i There are only a limited number of carriers in each cell ii When all carriers are being used the rate will be at a maximum f Facilitated diffusion i Objects are always moving from high contraction to low concentration there is a higher probability that something will bind to one side to move across when there is a high concentration of it ii No ATP used move down diffusion gradient iii Molecules bind to one side carrier reorients molecule leaves on opposite side more binding on high contraction side iv Movement from high contraction to low concentration g Active Transport I Movement from low concentration to high concentration i39 use ATP for energy to move ions against their COMCTRAFION gradient ons move from high affinity side to low affinity side AT produces the ion gradient across cell membranes NaK ATPase 1 Moves the sodium out of cells and potassium into cells 2 Potassium is high inside cells and sodium is high outside of cells 3 Crates gradients that allow electrical signaling vi Secondary Active Transport 1 Carrier has two binding sites agonist and sodium 2 Energy of the sodium gradient out to in drives SAT 3 Cotransport agonist in or countertransport agonist out 4 Sodium transports some glucose and amino acids in this way 5 In some tissues other ions drive SAT Lecture 6 Membrane Potential 1 Voltage N V V b V V V a Separation of charge b All cells have negative charge inside compared with the interstitial fluid c The opposite charges line up along the membrane d MB is always in the mV range Rising Membrane Potential a Voltage across cell membrane when the cell is not activated determined by open ion channels b k dominates at rest most open channels c Some Na contribution few open channels d Proteins are trapped by the cell unless Exocytosis takes place e Concentration i Protein can draw fluid to it when it leaves the blood vessels causes swelling when you are hurt f Permeability i The measure of how well things can move through that membrane determined by the number of open channels ii The number of open potassium or Sufism channels determines ion diffusion iii Different open number in different cell types produces different resting MP g NaK ATPase i This enzyme creates the gradients and restores them after ions diffuse across the membrane this is ion pump activity Equilibrium Potential a Limits on Kand Na b What voltage balances chemical gradients c Only open channels determine MP K Diffusion at Rest a At restmany channels are open and k diffuses out b Intracellular protein A is trapped in the cell c Na channels are mostly closed little Na diffusion PumpLeak Balance a Pump the sodium potassium ATPase b There is a balance between pump and diffusion channel activity i Some channels are always open some channels flicker on and off 1 Usually potassium channels a few are sodium c Since ions will consistently diffuse down their gradients through channels a constant input of ATP energy into ion pumps is needed to maintain the gradient Resting MP changes The membrane potential will change in many cells including nerve and muscle cells The MP is always negative at rest The MP magnitude decreases gets less negative during depolarization The MP increases gets more negative during hyperpolarization Depolarization i Cell that receives signal in brain hyperpolarizes and says quotnoquot 235 m V 1 It takes a high action potential to fire a neuron 2 Brain wants to rest as much as possible ii The membrane potential is less negative as from 70 to 60mV iii caused by k channels closing and Na channels opening iv MP movies toward Na equilibrium potential Hyperpolarization i The Np gets more negative as from 70 to 80 mV ii Caused by k channels opening Na channels closing iii MP moves towered kequilibrium pot etiology 7 Graded Potentials Triggered by agonists or by physical force b When you open a channel for a limited time the ions flow out and flow down the membrane when the channel closes then the ions released spread out and thin out and the membrane goes back to normal Size proportional to the stimulus spreads to adjacent areas but decays rapidly over time and distance Can only carry a signal over short distances Local potentials involve changes induced by some stimulus that is locks and limited by time and distance i In order to send signals over long distances f Occur in many cell types receptors neurons and muscles i In neurons and muscles GPs needed to reach threshold ofaction potentials v V m Lecture 7 Action Potential 1 Action Potential a Electrical signal long range in neurons and muscle b Don39t degrade over time and distance c Activated by graded potentials d Voltage gated sodium channels i Will open when the membrane reaches a particular voltage i39 Usually 15 to 20 mV above resting potential iii All vgated channels open together causing action potential iv Enter inactivated state soon after opening making refractory period 1 Order channels open up is always in one direction v Three separate states the sodium channel can be in 1 Closed but openable 2 Open a Turns on when the voltage gets to a certain place b Turns off by blocking itself c Open for one to two milliseconds d Makes thin side of the cell more positive voltage change will activate the next channel think of dominos 3 Closed and not capable of opening until they revert to the openable state inactivated vi Potassium channels 1 Either open or closed 2 Phases of the Action Potential a Controlled but different open channels b R is resting potential c This threshold d Depolarization to threshold firing level 1 i Chemical or mechanical gated Na channels open ii Na enters down gradient iii At t all voltage gated Na channels open iv TTX this is a drug and it is present in seafood blocks fast voltage gated Na channels e AP Spike 2 W J V i Since ALL voltage gated Na channels open together all APs in one neuron are identical 1 Open for one to two milliseconds and close into an unopenable state ii Na entersrapid depolarization to 20mv iii Doesn39t reach Na equilibrium potential because some voltage gated potassium channels are also open f Repolarization 3 i Voltage gated Na channels close after one to two milliseconds ii Potassium channel still open potassium leaves membrane potential falls g Hyperpolarization 4 i Voltage goes below resting because extra potassium channels are still open ii Nearer to 90 mV potassium equilibrium potential than at rest h Returning to resting potential 5 i Extra potassium channels close Neural Structure a Receive and pass on signals b No mitosis no cell division c Have the same neural cells you were born with d But you can create more connections e Dendrites i Receive neurotransmitter from other neurons ii Has many branches iii No action potential here only graded potentials 1 Graded potential is like a pebble in the pond creates waves a If you throw a bunch the waves will add up and become bigger 2 Adds up until you reach threshold f Cell Body i Cell organelles nucleus ii Axon hillock at beginning of axon high density of voltage gated Na channels 1 Axon hillock is at the junction of the cell body and the axon iii Actions potential starts here g Axons i Very long Carries AP away from cell body ii Speed ofAP variable increases with increase in diameter and with myelin 1 Myelin wraps around and insulate axon 2 Works the same as plastic costing on wires 3 More insulation faster signal h Myelin Nodes of Ranvier i Cell surrounds axons and wrap layers of membrane i39 Electrically insulates axon prevent electric loss to Interstitial fluid increases AP speed Myelin is white makes the brain appear white because of the fat wrapped around Nodes of Ranvier 1 Spaces between myelin that completes the AP circuit 2 AP jumps between the Nodes of Ranvier i Refractory Period i After voltage gated channel close they are unopenable for a time 30200 milliseconds ii No new APs during this time limits AP frequency iii AP cam only travel along axon in ONE DIRCTION you can39t go back Frequency ofAction Potentials a All APs are identical in a given cell b Information is passed by the frequency not the size of action potentials c More APs create a stronger signal a input to the CNs 53 Lecture 8 Synapses 1 N V U V b V U39I V Synaptic structure a Neuralneural synapses b Presynaptic neuron i End of axon synaptic knob terminal button Receive AP down Axon AP opens Ca channels Takes between 1020 nanoseconds to go across the space No receptors on the v presynaptic side vii Vesicles 1 Contains neurotransmitter 2 Increase in Ca triggers merger with cell membrane 3 neurotransmitter dumped into cleft space between diffuses to postsynaptic membrane Postsynaptic cell i Has receptors for neurotransmitter from presynaptic neuron ii Receptors connected to ion channels iii When neurotransmitter binds to receptor the channel opens up Excitatory Post Synaptic Potentials EPSPs a Neurotransmitter binds and sodium channels open b Sodium enters and causes depolarization c One EPSP is not enough to reach threshold you must have more than one Inhibitory Post Synaptic Potentials IPSP Potassium or chloride channels opened by euro transmitter Potassium leaves or chloride enters down their electrochemical gradient Membrane potential more negative Less likely to each threshold Vast majority make IPSP events you have more IPSP events that EPSP Potassium Grand Post Synaptic Potential GPSP a Sum ofall EPSPs and IPSPs b Reach threshold If so them the action potential is fired c Most neurons are inhibited by IPSPs most of the time d Different circumstances allow you to have control over certain movements i Pulling arm away from not stove nerves fire and your muscles contract ii Pulling child out of burning building nerves still fire and your muscles still want you to pull away but you can overcome that urge e Human behaviors can sometimes control action potential f Axon hillock i At the junction of the cell body and the axon ii High density of voltage gated sodium channels iii Action potential starts here Oneway Conductance a Neurotransmitter is only released from presynaptic neuron receptors only on post synaptic neuron b Information within only goes in one direction c Temporal summation i EPSPs from the name well am in time are additive they may sum to reach threshold ii Two separate events are close enough in time electrically to add together iv 5 n V m agggz are additive ii The sum of these May reach threshold iii Some neurons receive synapses from thousands of other neurons 6 Convergence a Multiple synapses into a single neuron b Anatomical basis for spatial summation c A single cell can only send EPSP or IPSP 7 Divergence a Each axon has many synaptic knobs terminal buttons to other neurons b An action potential In one neuron delivers neurotransmitter to all its divergent neurons at the same time c The action potential can send some IPSP or some EPSP because of what the neuron is connected to Lecture 9 Intracellular Communication 1 Communication types a Communication occurs between cells over short and long distances b Combinations of electrical and chemical activity i Sometimes chemical binding to a receptor 2 Gapjunctions a are the channels that go between cells that allow cells to activate the cell next to it b Good for heart bladderuterus small intestines for coordinated contraction 3 Paracrines a Locals hormones b Molecule released from one cell binds to a target cell next door c Causing a contraction decrease blood flow or relaxation increase blood floor d Nitric oxide important in control of blood flow 4 Neurotransmitters a Specific i Each neuron has only one type of neurotransmitter b Variable neural cell length i Neurotransmitter work locally when released c Neurotransmitters released by Exocytosis synapse celltocell i Work on the cell next to it d Neural to neural muscle endocrine cells e Rapid removal diffusion digestion reuptake f So neurotransmitters cam be used over and over 5 Endocrine a Hormones released from endocrine tissue endothelial origin b Broad effects hormone released into blood takes one minus to get to every cell i Goes everywhere c Effect depends on target cell receptor 6 Neurohormones a Released from neurons into the blood b Functions as other hormones receptor dependent i If there39s not receptor then there will be no effect 7 Hydrophilic hormones rst messenger a Most are small proteins all water soluble b Cannot cross the membrane i Stuck on the outside of a cell c Rely on membrane receptor activation d Receptor is connected to an enzyme which creates the second messenger e Membrane proteins produce second messengers 8 Second messenger a Made at the membrane b Internal activation mechanism started by hydrophilic hormone first messenger c Only cells with receptors respond d cAMP cyclic AMP i ATP gt cAMP 1 Activates kinases add phosphate to molecules ii Kinase cascades amplify signals 1 e1 gt e2 10 gt e3 100 iii Individualized effects in different cells 1 You cannot say in advance what the effect will be 2 Makes pharmacology difficult in terms of drug development 3 To find a drug what you want it to do that doesn39t have side effects is very difficult e cGMP i GTP gt cGMP activate kinase ii Doesn39t activate the range of enzymes like cAMP f P3 inocetrol triphosphate i Causes release of intracellular Ca stores ii Ca stored in sarcomas mic reticulum a structure modified from Endoplasmic reticulum 9 Calcium a Released from internal sarcoplasmic reticulum by P3 b Enters across cell membrane through Ca channels c Binds to and alters protein activity d Cell to cell Ca signal produces coordinated cilia waves Exocytosis i Cilia move in a nonsymmetrical fashion to move things away such as dust in lungs towards mouth e Smooth and cardiac muscles linked together by Gap junctions depolarization causes cardiac and smooth muscle contraction in adjacent cells by opening Ca channels 10 G Proteins a Timing proteins b Bind GTP gt increases activity until GTP gt GDP c regulate vesicle movement cytoskeleton growth vision second messengers d Astronauts take on a 39 hour day 11 Hydrophobic Hormones a Fat soluble Diffuse easily into cells b Need transport molecules in watery environment i Steroids thyroid hormone Vitamin A Vitamin D c Increase protein synthesis by activating genes d Widespread actions significant side effects e Nuclear receptors i Form interface between hydrophobic hormones and genes ii Downside in where the receptors are Will determine which genes activated by hydrophobic hormones iii Variations in gene activation in different cells is the basis for side effects f NeuralEndocrine comparisons i Neurons 1 Coordinate rapid precise brief responses 2 Electrical activity covers most distance NT diffusion distance small ii Hormones 1 Control long duration activity slower responses 2 More complex reactions long duration bringing of hormones 3 Takes minutes Lecture 10 Central Nervous System 1 Organization a The CNS is the brain and the spinal cord b The peripheral NS is the nerves that carry information into and out of the CNS 2 Affront neurons U V U39I V on V a Afferent neurons carry information into the CNS b Both conscious and unconscious information Efferent neurons a Carry information forth CNS to the body b Somatic NS neurons activate skeletal muscles c The automatic NS supplies neural input sympathetic and parasympathetic to most organs i The parasympathetic NS oversees the day to day homeostasis ii The sympathetic NS responds to emergencies 1 Something that scares you raises blood flow decreases digestion Interneurons a In the central nervous system more than 99 of all neurons b Perform all the neuron functions of the CNS i Thinking emotions memory etc Glial cells a Nonneural support cells in the CNS b Capable of mitosis have cancer potential i Unlike neural cells like in the brain ii You can hear of brain cancer but not heart cancer c Astrocytes i Star shaped hold neurons in proper physical positions ii Control neural growth and blood vessel growth in the brain 1 Blood vessels form blood brain barrier tight capillaries small pores between cells 2 Antibiotics cannot get across the blood brain barrier a You are in trouble if you need them iii Repair brain injuries and for scar tissue iv Degrade Neurotransmitters glutamate and GABA and control extra cellular K d Oligodendrocytes i Form myelin sheaths around axons 1 Responsible for white matter being white ii Limit neural growth in the CNS e Microglia i Immunity cells in the CNS ii Phagocytes move to areas of infection or damage 1 Engulf digest and recycle the cells iii Uncontrolled activity may or may not be involved in neurodegenerative diseases f Ependymal cells i Line the brains ventricles and secrete cerebrospinal fluid ii CSF Absorbs shock iii May be able to differentiate into other glial cells and possibly neurons g Cancer Potential i Because glial cells can divide they may be cancerous ii Neural cells do not divide and can39t form cancers iii The large number of glial cell types and subtypes make diagnosis difficult Nutrition a Brain needs a constant supply of glucose and oxygen to survive b No glucose storage needs constant blood supply c Glucose is small enough to get out of capillaries d Stroke reduces blood flow vessel blockage or breakage e Body can go 40 days without food 4 days without water and 4 minutes without oxygen f Desire to live cam change everything Cortex a Upper part of the brain the cerebrum b Heavily ridged 80 of brain i Ridging becomes more pronounced as a child grows Unique human qualities reside here such as voluntary movement conscious thought language morals many of these are in the frontal lobe d Lobes i Four major divisions in the cortex 1 Frontal movement control personality decisions moral judgment 2 Parietal somatosensory touch perception and proprioception position a Many more receptors on fingers touch and face than any other parts of body b More space devoted to those areas because of the number of receptors 3 Occipital visual integration a Sides of brain can produce a single image b Getting hit in the back of the head could break a blood vessel and cause damage to vision 4 Temporal hearing emotions Plasticity i No mitosis of neurons but learning involves making new synapses between existing neurons ii Practices motor activity enlarges controlling area of brain 1 Needs more neurons iii Area grows larger and involves more neurons iv f cortical input reduced areas receive input from adjacent areas v If cortical area is damaged adjacent areas can sometimes pick up lost function 1 There is no guarantee vi Language Control 1 Connection of sounds and symbols with objects 2 Broca39s area In frontal lobe a Speech formation b If you have a deficit in this area you will have difficulty forming words spoken or written i Stutter 3 Wernicke s area in temporal lobe a Comprehension ofauditoryvisual information b If you have a deficit in this area you may form sounds but they contain no content i You don39t know what others are saying and you don39t know what you are saying Can39t communicate easily with other people c Hearing is the heard east sense to live very valuable sense more valuable than sight Association areas i Higher brain functions association contexts integrate multiple inputs ii Prefrontal AC controls planning and morals iii Parietal temporal and occipital AC makes coordinated world view links touch sound and sight Hemispheres i Right side visual spatial relations aesthetics controls left side ii Left side analytical processing and language development includes Wernicke s and Broca39s area controls right side iii Geniuses use both sides of the brain Electroencephalogram i Measures Background electrical activity of the brain ii Recording on the surface used for determining if someone has died 1 Not measured by heart of breathing activity I m V a Uh V 339 V Lecture 11 Subcortical Structures 8t Memory 1 Sub cortical structures a Structures below the cortex that control different functions b Shared with other mammals c Basalnuclei N V m V Collection of five structures on each side of the brain Below the cortex to the sides of the thalamus Connected to each other and to the cortex Postural control is nonconscious Feedback loop correct posture variations Decreased concentration of dopamine linked to Parkinson39s disease 1 Basal nuclei end up over contracting the muscles 2 Muscles stay contracted Muscles that usually oppose each other also stay contracted causing shaking biceps and triceps People who have Parkinson39s disease have slow movements and shaking 3 Prefrontal cortex is not involved in Parkinson39s diseases people with Parkinson39s can thinkjust fine it just takes longer Thalamus i Receives sensory input from the opposite side ii Directs and edits input to the central cortex iii About 98 of inputs blocked ignored from reaching the cortex iv Cortical focus allows information through thalamus v One type of autism possibly the most common type may be due to lack of thematic editing 1 Too much information gets into the cortex they havea difficulty ignoring things 2 Learn best when put into an environment with minimal distractions 3 Other forms of autism don39t allow any information in Hypothalamus hypo means under i Monitors Homeostasis 1 Temperature thirst milk release hunger reproductive urges Circadian rhythms increase emotional feelings ii Hypothalamus can see what39s wrong the cortex decides what to do 1 If you feel cold it can detect it though changes in blood temperature 2 There is no preplanned response the response is in the cortex 53 S Limbic system a Ring of structures underneath the cortex of the cerebrum b Two important functions Detects emotions and memory formations c Hippocampus is part of the limbic system d Can39t control any movements in your body can39t make you do anything you have to want to do it e Emotions i Feelings about things ii Reproductive drive rage fear motivation iii Cortical decisions few connections to cortex limited cortical control of emotions iv Can39t make emotions just go away it takes time and distraction v Cortical control is over responses limited input of limbic system to motor areas no compulsory action f Neurotransmitters i Norepinephrine dopamine and serotonin are the neurotransmitters in the limbic system ii Altered concentrations of Neurotransmitters have been 39with 39 r 39 39 39 r use receptors for these Neurotransmitters 1 14 people may have worse feelings after taking medication iii Excess dopamine has been linked to schizophrenia limits Ldopa Parkinson39s treatment Memory a Retention storage and ability to recall information b Memory traces are sequences of neuronal activations n V i Continuous loop ii Declarative memory facts event swords language rules 1 Hippocampus and total lobe for storage iii Procedural memory unconscious physical skills habits tasks 1 Cerebellum plays a major role Short term memory i Seconds to hours ii Alters activity in existing neurons in hippocampus iii Can be erased and replaced Long term memory i Creation of new synapses and memory traces ii Make multiple copies of important memories over the years iii Retain youthful memories as you age iv Transferred from hippocampus to cortex 9 V e Working memory i In the prefrontal association cortex ii Compares newly acquired short term data and stored long term data iii Determines relevance of new materials organizes priorities f Amnesia i Affects ability to recall i39 Inability to recall stored information iii Retrograde 1 Caused by trauma loss of short term memory 2 No long term memory formation of traumatic events 3 No long term memory loss Nothing to recall later iv Anterograde 1 Hippocampus damage can39t form me long term memories 2 No loss of previous long term memory 3 Memory stuck on day of damage 4 Can be caused by strokes Lecture 12 Cerebellum Sleep and the Spinal Cord 1 N V U V Cerebellum a We have a very good understanding of the cerebellum b Structure on the back of the brain stem c Controls coordinated movements and learned movements d Balance i Maintains balance and controls eye movements 1 Eye movements tell you where are in space 2 Vestibular apparatus is triggered when you spin around in circles makes you feel dizzy because your eyes think you are still moving e Coordination i Connected to the motor cortex receives motor plan i39 Afferent input gives correct muscle position As you practice the motor cortex parietal lobe and cerebellum take over 1 Need to practice well and precise so that you create a motor plan iv Planning is reduced initiation of activity is a faster and smoother input to cortex f Input to cortex i Allows cortex to know current position and movement ii Cortex uses this information to plan future movements 1 Grunting during tennis covers up the sound of the ball hitting the racket covers up cues Brain stem a Medulla pons midbrain are all parts of the brain stem b Midbrain is the interface between spinal cord and higher brain centers c Cranial nerves supply sensory and motor function to head and neck d Different centers in brain stem control heart rate breathing and wakefulness Reticular activating system RAS a Controls wakefulness consciousness and sleep U39I V 5 i When the RAS is on the rest of your brain is on and you are awake ii When the RAS is off the rest of your brain is off and you are asleep b Neural net awareness of surroundings c Cortical plan auditory and visual input d Output to cortex and thalamus all cortex Sleep a Low frequency activity in hypothalamus and thalamus gt sleep b Reason needed is unknown c Can t deprive yourself of sleep i Believed that if you deprived someone of sleep you could turn them into schizophrenic ii Denial of sleep is a form of torture d EEG Patterns i When you are awake ii Slow wave patterns in EEG give slow wave sleep its name iii EEG pattern during REM sleep is similar to being awake e Slow Wave Sleep i Four stages each becomes progressively deeper over a 75 minute cycle 1 Drifting off dreaminess 2 Brain produces short periods of rhythmic brain waves for about 20 minutes 3 Deep slow brain waves known as delta waves 4 Deep sleep that lasts for 30 minutes ii Circadian rhythm that is controlled by g proteins9 adenosine part of ATP increases 9 sleep iii Coffee blocks adenosine response iv Sleep factor muranyl dipeptide 9 strong sleep inducer need massive quantities f Rapid Eye Movement Paradoxical Sleep REM i 15 long at the end of a slow wave sleep cycle i39 Paradoxical sleep hard to wake someone up during REM sleep most likely to wake self High activity in visual cortex low activity in frontal high activity in memory areas 9 dream 1 Have vivid illogical dreams low cortex activity leads to illogical dreams New synaptic contacts made 9 increase in long term memory 1 Will make up missed REM sleep v Daydreams are different than deep dreams Spinal Cord a Nerve tissue enclosed in vertebral column b Carries action potentials between the brain and body c Gray matter in the middle cell bodies and interneurons d White matter on the outside myelinated neuronal tracts e Trad i Bundles of neuronal axons that carry action potentials ii Ascending tracts carry action potentials towards the brain iii Descending tracts carry action potentials from the brain to efferent neurons f Dorsal roots i Split as they approach the spinal cord ii Entry points for afferent neurons to the spinal cord iii Afferent cell bodies are in the dorsal root ganglia 1 Afferent into the CNS 2 Ganglion cluster of neurons in a particular place g Ventral r001 i Carry efferent action potentials out of the spinal cord 1 Efferent out of the CNS to the body ii Cell bodies of efferent neurons in the gray matter iii nformation carried via action potentials Re exes a Neural response without a conscious input from CNS b You can influence some but not all i Touch hot stove 9 afferent neurons 9 information processes 9 efferent neuron 9 reflex muscle Re ex Arc i Five specific parts 1 Receptor that interacts with the environment 2 Afferent Neuron sends information from the site of the interface over a long distance to the CNS 3 CNS processes the information needs at least one synapse n V 4 Efferent Neuron sends information to an effector cell 5 Effector cells might be a gland or muscle Monosynaptic reflex one synapse Polysynaptic reflex multiple synapses 1 Between afferent and efferent neurons Withdrawal reflex i Polysynaptic reflex multiple synapses ii Multiple neurons between afferent and motor neurons iii Prolonged activation to try to remove the particular stimulus iv Makes withdrawal reflexes very strong but with potential CNS input Stretch reflex i Tapping your knee and your leg kicks up monosynaptic reflex ii Lengthening the muscle sends information into the CNS iii Produces a reflex Monosynaptic reflex kneejerk reaction iv Activation of afferent neuron directly to efferent neuron produces reflex 1 There s no other neurons to process this 2 No control by upper CNS a Still have conscious control over the muscle but you can t stop the knee jerk reaction m V Lecture 13 Afferent Nervous System Pain Taste Smell N V Sensory Receptors Sensation a Connect an environmental signal to the body b Transduction is the conversion of a stimulus to the physiological signal c The brain converts the physiological signal into a perceived sense Stimulus a Environmental signal b Binds and changes a receptor signal now in body c Each receptor binds one stimulus best i What stimulus needs the least amount of energy to activate a particular receptor Sensation a Conscious senses five sense also time i Because of g proteins allows brain to interpret the passage of time ii Feeling hot after a fever means you are over the fever now your body just have to wait for the blood to change temperature b Unconscious senses position temperature BP changes i Blood pressure medication makes your blood pressure go down homeostasis then makes your body want to bring your blood pressure back up Types of Receptors a Must bind to the stimulus no dendrites on receptor cells i Except for sense of smell Modified receptor ending with nerve endings to interact with stimulus Physical i Physical changes open ion channels ii Changes membrane potential 35 iii Touch receptors hair cells in ears photoreceptors baroreceptors pressure receptors d Chemical i Chemical receptors are associated with Taste and smell ii Chemoreceptors chemical bonds receptors opens channel and changes mp 1 Almost always opens sodium channels except for sense of sight that causes a depolarization of a membrane e Receptor potentials i Also called generator potentialslocal potentials i39 Graded potentials are not strong enough to create a long impact iii Depolarization of receptor cells Size of potential proportional to size of stimulus Receptor fields vary in size depend on the number of afferent cells 1 If you were to poke yourself with something that has several points you might feel more points on your hand than your back Magnitude 1 More stimulus 9 greater receptor potential RP 2 In receptors without AP release of NT proportional to RP vii Frequency Dependence 53 lt c 5 Adaption a Decreased action potential number dispute prolonged stimulus b Getting used to clothes on your shoulders getting used to having problems breathing through on nostril or having a floater in your eye etc c Phased receptors i Adapt over time rate is variable 1 Touch receptors adapt quickly 2 Pain and blood pressure receptors adapt slowly a Body telling you to change something to get rid of the pain i Some people are born without pain receptors but a life without pain is not a life without problems b If you have a high stress job your body will stop thinking of your blood pressure as high instead think of it as normal d Tonic receptors i Do not adapt ii You have very few of these ex includes smell receptors 1 Can adjust to a smell and then as soon as someone reminds you of it you can smell it again iii Postural receptors in trunk are near tonic 1 Keep you in an upright position and are controlled by the basal ganglia 2 Ex soldier that stand still for too long and then tries to walk may fall over Sensory speci city a Normal stimulus produces a response that the brain interprets b Different stimulus needs more strength for a response c Brain still interprets as quotnormalquot response getting hit in the eye produces a visual sight such as seeing stars Pain Survival value protects you from harm b Anticipation of pain activates same pain areas in cortex i Whether you are actually hurt or you anticipate that it will hurt your brain perceives it the same way Nociceptors pain pathway receptors are both chemical and physical Fast pain i Sharp localized and passes quickly such as getting a shot ii Fast large myelinated afferents use glutamate as a neurotransmitters Slow pain i Most pain is slow pain ii Diffuse dull long lasting 1 93 V m V iii Slow Unmyelinated afferents use quotsubstance p neurotransmitters Substance p p stands for pain i Presence suspected before discovery ii Neurotransmitters unique to afferents slow pain neurons iii People that deny pain medication because of long term pain may not react to pain medication when it is needed because the body is so used to the pain Opioid receptors i Natural analgesics block pain by binding to opioid receptors ii Activation alters ion channels and membrane potential iii Enkephalinsendorphins 1 Enkephalins means all in your head 2 Peptides multiple eyes different sizes 3 Enkephalins and endorphins have a Short halflife 25 seconds 4 Morphine is effective for hours Chemical senses i Molecular binding to receptor ii Flavor is a combination of smell and taste 8 Taste a Molecules dissolve in saliva and reach taste bud receptors to be tasted i Hydrophilic substances are more likely to be tasted than hydrophobic substances that float on your saliva b Taste buds i Receptors at taste pore ii Tight junctions are at the top of the taste buds and keep saliva away from rest of taste buds 1 Also keeps bacteria away from the inside of the tongue doesn t stop you from tasting food iii Surrounding epithelial cells gt basal cells gt receptor cells iv Turnover of taste cells on the surface of the tongue is at about is about ten days c Neural tract i Sensory neurons send taste information ii Neurons to thalamus parietal lobe quotwhatquot taste iii Neurons to limbic system quotlikequot it d Taste receptors i Salty sensitive to Na ii Sweet sensitive to organic sugars iii Acid sour hydrogen iv Bitter bases quinine activated by cation poisons most sensitive receptors v Umami glutamate msg v V Uh V 339 V a Olfactory mucus membrane on roof of nasal cavity b Merge than 1000 different odor receptors c Largest gene family make up more than 1 ofall human genomes cl Two requirements i Molecules must diffuse through mucus water soluble and bind to a receptor to activate ii Must be volatile enough to float to the top of the nasal cavity e Need least number of molecules to detect garlic f Natural gas has no odor but if you leave the gas tap on you can smell the essence of garlic that is mixed into it so that you can detect it g Least likely need most amount of molecules to smell ethyl ether h Olfactory receptors i Part of dendrites of olfactory neurons ii Covered by mucus 1 Usually believed that neurons do not experience mitosis iv Unusual these are tonic receptors dendrites as receptors new neurons i Olfactory adaption i Unusual receptors are primary tonic ii Unusual most adaption in the CNS brain can overcome adaption iii Adaption to one smell doesn39t affect the other Lecture 14 Vision 1 Structure of the eye a Designed to receive light and produce electrical signals b Cornea i Clear noncellular front of the eye ii Light passes through not refracted bent c Lens ciliary body i Lens refracts light to focus on retina ii Muscle contraction for near vision causes lens to round up iii Muscles relax for distance vision iv Lens hardens as you get older people that wear glasses will need bifocals by age 45 d Iris i Opens and closes pupil ii Smooth muscle contractions adjust to light level e Aqueous humor this liquid in the eye i Between cornea and lens ii Constant production and drainage provides liquidification for inner eye keeps it from drying out iii Glaucoma decrease in drainage or excess production leads to an increase in pressure which leads to retinal damage 1 People with perfect vision are the ones who tend to get glaucoma because they never go to the eye doctor iv Beta blockers decrease production causing cholinirgin agonists to increase drainage f Vitreous humor i Gellike bulk of eye volume ii Between lens and retina maintains eyeball shape iii No refraction perfectly clear so light can just pass through iv Vitreous retraction pull away from the back of your eye can break blood vessels g Retina i Visual receptors at the back of the eye ii Multiple cell layers iii Many photons pass right through h Choroid i Highly pigmented layer behind retina ii Absorbs all light that enters iii There is NO reflection no signal iv Pupil looks black because the choroid absorbs all light and no light is able to bounce back 2 Refraction a Bending of light waves b Glycoproteins in lens refract light focus it on the retina 3 Retina Light passes through bipolar and ganglion cells to reach photoreceptors Bipolar and ganglion cells pulled back at fovea You teach yourself to move your head so that light goes into your better eye and reaches the fovea Fovea has best color vision dense cone concentration i One in each eye e Rods are more sensitive at picking up light 1 35 U39I V f Photoreceptors i Most are rods but those are usually located away from the fovea ii Rods pick up shades of gray have more photoreceptors 1 More sensitive at picking up light 2 Farther away from fovea Cones have color receptors few overall receptors 1 Have fewer cones but have a higher concentration right at the fovea Rods and cones produce neurotransmitters which is proportional to receptor potentials no action potentials v Both converge on bipolar cells g Bipolar cells i Activate the center of a bipolar cell will turn off the six bipolar cells around it 1 Produces a sharp edge around it 2 Produces an onoff effect that is digital and creates an quotedge effect ii Generator potentials activated by rods and cones iii No action potentials they have a synapse with ganglion cells h Ganglion cells i On the inside of the eye ii Straight long neurons that fire action potentials iii Reach threshold and fire action potentials that leave eye for central nervous system iv Carry visual information to lateral geniculate part of the thalamus 9 to the cortex v You have a blind spot in both of your eyes Optic nerve a Bundle of ganglion cell axons b Creates blind spot as axons pass through the retina c Cortex fills in blind spot with expected image d Lateral geniculate i Receives information from ganglion cells ii Edits information that goes into the cortex iii Decides what information to pay attention to shaped colors etc e Visual cortex i Multiple areas In occipital lobe ii Integrates input of visual perception iii Relative positions 3D images iv If a child has a lazy eye then cover the stronger eye and force the lazy eye to being working 1 People with two sets of vision don t have two different views they usually just have one because the brain can t integrate them Accommodation a Requires that you change the thickness of the lens Change in thickness alters focal point for near and far vision i Close to eye need to bend the light waves so you need thick lenses ii Thin lenses are better for far vision Ciliary muscles control focus Presbyopia i Lens gradually harden over decades ii Hardening reduces founding of lens for near vision iii At 4045 years old difficulty focusing on near objects 1 Reading glasses and bifocals 2 Harden in the distance vision location 3 Vision correction surgery does not stop lens from hardening a Need additional surgery or glasses 4 Some people get surgery so that they can see far with one eye and close with another you give up 3D vision and lose your depth perception 93 V e Myopia and Hyperopia i les more people are near sighted than far sighted i39 About half of the human population has myopia iii Both cause an inability to focus on retina iv Myopia near sighted eyeball too long focus in front of retina can see up close but have bad distance Vision v Hyperopia farsighted eyeball too short focus behind retina can see far away but have bad close vision vi Corrective lenses surgery on cornea 6 Rhodopsin a Protein b Visual pigment in rod cells c Combination of opisin and retinene Vitamin A derivative d When light hits retinene and partially removes it from opisin bleaching i Bleaching is switching from on position to off position if your eye is bleaching you can39t absorb any more light waves e Opisin now active g protein system recycles 14 timessec f System changes membrane potential releases neurotransmitter g Retinene rebinds to opisin it turns it off and you await more light to turn it on again 7 Color vision a Three different opsins with retinene i Shading of retinene limits frequency range ii Peaks at red also sees yellow green and blue wavelengths b Green is most common type of colorblindness i Gene is on the x chromosome c Color blindness i If you are colorblind then one opsin is missing ii Can39t distinguish certain wave lengths because they have equal activation of opsins Lecture 15 Hearing and Equilibrium 1 Outer ear a Little amplification associated with it at all b Sound waves reach the ear at different speeds sound has to travel around your head to get to both ears i Changes the frequency ii Allows for direction detection with the exception of a sound that is along the main axis of your body iii Includes ear canal c Tympanic MembraneEardrum i Overlapping membranes ii Separates outer and middle ears iii Vibrates to external air waves iv Can heal itself and will reseal if broken 1 Hear a static noise and then all at once it sounds better 2 Middle Ear Filled with air Amplifies sound by 20 fold Amplification works because of ear bones Ear Bones i Hammer malleus ii Anvil incus iii Stirrup stapes 1 Stirrup is the place where amplification occurs iv Carry waves from tympanic membrane to oval window In 935 V V v Bones shrink and cause separation causes the sound waves to not pass through from one bone to the next need a hearing aid which causes amplification of sound waves and bypasses the bones e Eustachian tube i Eustachian tube drains fluid from the middle ear 1 Drains from middle ear to sinuses Has to pass through facial bones ii Equalizes air pressure between middle ear and sinus 1 When you feel your ears pop you are feeling the opening of the Eustachian tube iii Infections can cause problems breathing hearing and pain Pain may be associated with the Eustachian tube because liquid is being forced through a small hole in the facial bones iv Normally closed but responds easily to pressures 1 if unopenable tubes are needed in the eardrum because the hole in the facial bones is not big enough f Oval Window i Membrane connects middle ear to the inner ear ii Send sound waves into cochlea 3 Inner Ear a Fluid filled b Converts sound waves to electrical signals c Cochlea also called Organ of Corti i Cochlea Spiral shaped tube of inner ear ii Snaillike fossils are called cochlea Harry Potter reference 1 Organ of Corti spiral shaped this is the part of cochlea that transduces sounds to action potentials 2 Waves carried to apex and back to round window it gets wider as it goes 3 Round window absorbs all sound waves no action potentials a Similar to choroid in eye Choroid in eye is the pigmented area behind the retina that has photo pigments absorbs light prevents reflections so you don t see multiple images b Round window absorbs all sound waves and doesn t allow them to be reflected back prevents echoes 4 Cilia connect the basilar membrane to the tectorial membrane iii Basilar Membrane 1 floppy 2 Vibrates to sound waves shape changes over lengths 5 fold change 3 High frequency at base not very wide low frequency at apex center of the cochlea broader area Helps you detect different sound frequencies depending on where the sound wave hits Highest frequency humans can detect is 20000 Hz Highest frequency 20 year olds can detect is between 17000 to 18000 Hz because the basilar membrane grows thicker as you age starts at age 6 Professor can probably only hear 14000 Hz Lowest is 20 Hz Never lose low frequency iv Hair cells cilia 1 Rest of basilar membrane and are imbedded in tectorial membrane a Activates a generated potential that becomes the signal that is interpreted by the brain as different sounds v Tectorial Membrane 1 Much stiffer than basilar membrane less movement 2 When basilar membrane vibrates the imbedded hairs are pulled on 3 Hair cells produce grade potentials 9 neurotransmitters to afferent neurons 9 action potentials to central nervous system by auditory nerve 4 Tectorial membrane is very stiff all around 4 Frequency of Sound a Maximum range 20 Hz to 20000 Hz i Hearing is most sensitive at 3000 Hz ii Middle C is 440 avg 30 U39I an I V n V b Lose high frequency hearing with age c Narrow stiff end at the end of the basilar membrane near the oval window detects highest frequencies i Farther in you go the lower the frequency it can detect d Timbre i Overtones allow source distinction 1 Associated with types of musical instrument or individual voice a Same fundamental note can be played by different instruments but different frequency vibrations tell you which instrument is playing it b Higher frequency overtones help distinguish voices ii Total signal fundamental frequency overtones 1 Smaller overtone more pure note Amplitude of Sound a Higher the sound wave higher wave more hair cell movement and more action potentials to the brain b More action potentials louder sound Deafness a Loss of hearing b Conductive most common kind of deafness i Sound waves don t reach hair cells ii May be caused by wax eardrum damage middle ear bone damage 1 Older people will typically have middle ear bone damage because the ear bones separate with age 2 Hearing aids help they amplify sound to vibrate oval window directly c Nerve Deadness i Damage to hair cells or auditory nerve ii Need cochlear implant to treat iii Frequency deafness loud repetitive sounds at one frequency pull out hair cells in one place and causes selective hearing loss iv Should children embrace their deafness or get cochlear implants Equilibrium a Vestibular apparatus detect changes in motion i Five structures 3 semicircular canals b RotationalAcceleration i Three semicircular canals at the right angles to one another 1 Detect motion as you turn cartwheels summersaults rotating ii Fluid filled as fluid lags motions fluid pulls out hair cells iii Copula has hairs of hair cells embedded in its base iv Semicircular Canals 1 Hair cells imbedded in cupula inertia a If it moves one way then the brain can interpret the rotation 2 Generates graded potentials 9 action potentials 3 When hard rotation stops 2530 seconds to reequilibrate Linear Acceleration i Detects change in speed ii Hair cells imbedded in gel with otoliths ear stones 1 Acceleration pulls on hair cells iii Utricle and Saccule 1 Utricle detects horizontal motions front back left right 2 Saccule detects up and down motions 3 Set up at right angles to one another 4 Mismatch of signals 9 motion sickness because of excess or loss of signal a Some people that want to be astronauts are not able to handle the motion sickness caused by the loss of the signal from their saccule Lecture 16 Efferent Nervous Systems 1 Efferent neurons come out of the Central Nervous System causing different changes to occur in the body a Autonomic nervous system parasympathetic and sympathetic nervous system Sympathetic Structure a Part of the autonomic nervous system b Sympathetic chain ganglia parallel to spinal cord i Ganglia collection of neurons where the neurons synapse Input from cord medulla and hypothalamus Cortex cannot directly activate i You have to know that something is dangerous and interpret it that way before producing a response can t have a response if you re asleep Preganglionic Neurons i Short neurons ii Use 39 39 39 id Ach as 39 Ler to activate postganglionic neurons in ganglia iii Action potential goes from preganglionic to the postganglionic to some tissue Postganglionic Neurons i Long neurons ii Activated by preganglionic neurons 1 V 93 m V n V 1 Response is not dependent on their neurotransmitter but the receptors that are present Response produced depends on what it binds to iv Adrenal medulla behaves like postganglionic neuron stores small amounts of epinephrine adrenaline and norepinephrine circulates through blood stream when in danger creating hormonal activation 2 Sympathetic Responses a Responds to emergencies b FlightFight response i Designed to remove danger ii Increase in blood flow to skeletal muscles increase heart rate and blood flow to heart 1 Concurrent activation of motor units Sympathetic neurons help activate all neurons nearly simultaneously so that you can react with the most amount of force possible iii Decrease activity of digestive system and related functions Receptor Types adrenergic receptors i Activated by sympathetic neurons i39 All bind norepinephrine from postganglionic neurons iii Alpha 1 Both 1 and 2 cause increase in tissue activity 2 Alpha 1 9 increase in IP3 9 increase in Ca release from SR 9 increase in Ca 3 Alpha 2 9 decrease in cAMP 9 decrease in Ca pump 9 net increase in Ca a Both result in an increase in Ca just by different mechanisms causes the muscles to contract more iv Beta 1 only present in the heart 1 Increase Ca in heart 9 opens Ca channels 2 Increase heart activity 3 Beta blockers decrease strength of contraction in heart a Beta 1 receptors are only present in the heart so Beta blockers only affect the heart and nowhere else in the body v Beta 2 1 Increase in cAMP 9 increase in Ca pump 9 decrease in Ca opposite of Alpha 1 2 Decrease in blood vessel contraction and decrease in lung activity a You only use 10 of your lungs normally b Bronchiole constriction 9 more blood more air 3 Parasympathetic Structure a Handles daytoday nonemergency situations 391 V h V U39I V l V b Part of the autonomic nervous system c Two neuron series all neurons use Ach as neurotransmitter d Cholinergic activation controls daytoday homeostatic maintenance e Preganglionic Neurons i Long presynaptic neurons travel from spinal cord to organs ii Synapse at ganglia on organs with postganglionic neurons f Postganglionic Neurons i Short neurons travel from the ganglia to the cells Parasympathetic responses a Decreased heart rate i Average heart rate is 7275 but your heart rate increase when you exercise 9 body will try to bring the heart rate back down sometimes lower than before ii No parasympathetic input 100 beats per minute b Increased GI contractions and secretions i Smell food 9 stomach grumbles c Increase pancreatic secretions d Contracts urinary bladder e Relaxes internal anal and urinary sphincters AgonisBAntagonists a Pharmaceuticals can mimic or antagonize autonomic nervous system agonists like modium i Diarrhea is from increased contractionsactivity in the small intestines you take modium to decrease those contractions but may also have effects on your bladder Parasympathetic nervous system increase or decrease in digestive activity Sympathetic nervous system increase blood pressure in shock decrease in hypertension Drugs in the parasympathetic and sympathetic nervous system may have MANY side effects Motor Neurons skeletal muscles a Alpha motor neurons get multiple inputs up to 10000 i Input from stretch receptors withdrawal reflexes cerebellum learned activities cortex conscious control b Both PSPs and EPSPs to alpha motor neurons Neuromuscular Junction NMJ Motor neuron synapse with skeletal muscle fiber cell b Motor end plate very large synapse c Acetylcholine Release i Presynaptic Action potential 9 Ca energy 9 Ach release 9 Ach binds receptor 9 increase in Na entry 9 threshold ii One motor neuron action potential leads to one muscle action potential 35 In iii Control of motor neuron action potentials control muscle activation Endplate Potential i Endplate potential much larger than EPSP ii Ach binds receptor 9 increase Na entry 9threshold iii 1 motor neuron AP leads to 1 muscle AP iv Control of motor neuron Aps controls muscle contraction D V e Acetylcholinesterase AchE i AchE degrades Ach to choline and acetic acid ii Reuptake of choline diffusion away of acetic acid f NMJ Poisons i Many poisons affect the diaphragm can t breath 1 Black widow spider venom 9 releases all Ach you can t contract again and die of asphyxiation 2 Botullintoxin botox 9 blocks Ach release 3 Curare 9 blocks Ach receptors keeps the muscles from retracting Lecture 17 Muscle Structure and E C Coupling 1 Striated Muscle Structure m b l I amp m V n V Uh V Striped appearance under a microscope Skeletal muscles are connected to bones by tendons i Have voluntary control over skeletal muscle ii Run the entire length of the bone Cardiac smaller cells attached endtoend i Don t have control Smooth muscle has the same type of filaments but they don t have the striped appearance because they aren t in register i Don t have control over smooth muscle tissues ii Register lined up together like uncooked spaghetti noodles Muscle Fibers i Muscle Cell muscle fiber ii Runs length of muscle in skeletal muscle iii Skeletal muscles are 50 microns across and are very long these are big muscles iv Change size thickness but do not go through mitosis do not reproduce 1 Growth occurs by changing the size of the cells by putting more filaments into the cells 2 When you have a cast taken off you don t lose muscle cells you just lose filaments in the cells v Satellite cells look they like were never linked up to the whole can undergo mitosis have stem cell qualities Striations i Lines in skeletal and cardiac muscle ii Darker and lighter colors in muscle is due to filaments lines up in register creates stripes iii Filaments overlap overlap increases during muscle contraction 1 Uses ATP iv Dark and light bands 1 Dark bands contain thick filaments may also have thin filaments a Changing the length of the muscle causes the dark bands to stay the same width but the light area will increase its width 2 Light bands have no thick filaments only thin filaments 3 Thick filaments light cannot pass through cannot change width b Thin filaments light can pass through can change width 3 Cross bridges reach actins in the thin filaments the 39 39 muscle shortening v Sarcomere 1 Distance between two 2 lines is called the sarcomere this is called the quotUnit of contraction from 2 line to 2 line 2 Thin filaments are anchored to 2 lines 3 Thick filaments connect to thin filaments during contraction 4 What one sarcomere does all do Thin laments i Three proteins actin tropomyosin and troponin ii Actin is the polymer backbone double stranded helix 1 Grass has actin filaments that gives it stability 2 Could take the actin out of grass and put it in your heart and it would work just fine 3 Actin is present throughout nature and is interchangeable 4 How much K do you need to have the actin turn from globular to filamentous gt50millimolar high concentration of K in cells you have actin filaments in all cells iii Tropomyosin long thin protein polymer runs along actin 1 Each molecule covers about 6 V2 actins 3 Covers actin like a cable quot 39 for force I o is N V iv Troponin binds to tropomyosin 1 End of each tropomyosin is a molecule of troponin 2 11 ratio v Both are important in controlling muscle movements vi High potassium concentrations inside cells can convert actin into actin filaments Thick laments i Made out of Myosin polymer of filamentous protein ii Cross bridge is the extension of myosin molecule 1 Can bridge the gap between the thick and thin filament iii Cross bridge head can bind to actin and generate force TTubulesSarcoplasmic reticulum i Ttubules are at the ends of the thick filaments ii TT s are invaginations of muscle membranes carry action potentials into muscle fiber interior iii Sarcoplasmic reticulum is a modification of the endoplasmic reticulum stores Ca 1 Connected to TT by voltage sensitive protein iv Action potential own TT opens Ca channels in sarcoplasmic reticulum v Calcium is drawn by a diffusion gradient to pass over the overlap of the thin and thick filaments ExcitationsContraction Coupling a Activation of the muscles b Electrical events leading to muscle contraction c Excitation activate or contract d Skeletal action potential i Starts at NMJ synapse ii 1 AP down neuron 9 1 AP in the muscle iii Neurotransmitter Ach binds to receptor opens Na channels and starts action potential to spread in both directions e Release of Calcium i At ttubule action potential travels inward alters protein in ttubule leading to the opening of Ca channels in SR near TT Ca released ii Ca pumps at middle of ASR requesters 1 Ca and causes relaxation f TroponinCalcium Binding i Ca binds to troponin on thin filaments g Tropomyosin Shift i Cabound troponin causes tropomyosin to shift into actin groove exposing AM bonding site h ActinMyosin Binding i Actin and Myosin connect ii Myosin already has ATP bound and converted to ADPPi with ADPPi still bound iii Force generation 1 Occurs when ADPPi released 9 myosin shape changes head twists leading to force development 2 No filament sliding no change in overlap 3 PI release is key to force development iv Filament Sliding If the force that the muscle can generate is greater than the load you have to pull on then the filaments will overlap and move to a shorter position 339 V V E 2 Filaments slide to decrease force on cross bridge head more overlap 3 Goes to lowest energy state force 0 4 New ATP binds to myosin actin is released and process repeats as long as Ca is elevated Relaxation a Cessation of APs stops Ca release from sarcoplasmic reticulum b Calcium pumps return released Ca to sarcoplasmic reticulum c Tropomyosin reblocks AM binding site d When you don t have any calcium the muscle relaxes Lecture 18 Skeletal Muscles 1 in V on V Motor Unit a Motor units may activate up to 100 muscle cells b Motor neuron and muscle fibers in innervates c Motor neurons action potential activates all the fibers in a motor unit d Recruitment i You turn on the smallest motor units first then larger ii Allows gradiation of force iii Maximum force requires all motor units active simultaneously e Asynchronous not at the same time recruitment i For maximal forces rotate activation of motor units allows you to maintain force for a longer period of time ii In order to maintain force cannot simultaneously optimize force and continuous activity iii If you do an activity often you will become better at generating the force needed for that activity 1 Practice makes you better at a particular activation Twitch a Single muscle activation b 1 neural action potential 9 1 muscle action potential 9 1 twitch force produced by a single action potential i 1 twitch is the smallest amount of energy that can produce a movement c Submaximal force not enough Ca reaches all troponin for full activation d Lasts for 100ms Tetanus a Summation of twitches many action potentials b Enough Ca so that all myosin heads reach actin LengthTension Relation LE m b Resting skeletal muscle length is near LO c Falloff at Long Lengths i Reduced overlap of thick and thin filaments ii Falloff at Short Lengths 1 Thick filaments compression against 2 line 2 Thin filaments overlap and interfere with each other so you can t get all of the myosins to the actin because there is a filament in the way 3 Reduced Ca release at short lengths for three reasons 4 Reduced Ca release at long lengths for one reason a he mentioned a multiple choice question Force Velocity Relation a Heavy loads can only be moved slowly b Light loads are moved quickly c FO Optimal Force d Inverse relation i High force load 9 low velocity ii Low force load 9 high velocity Stretched muscles a Stretching before activation winding up before throwing a ball uses top of LengthTension LT curve b Better force maintenance c Also activating stretch reflexes 9 reflex contraction of stretched muscle i Our bodies are meant to pitch underhand pitching overhand can develop problems d Inhaling does not trigger a sympathetic response i Exhaling too fast may activate sympathetic neurons because the body feels like it doesn t have enough air ii Therefore there will be a simultaneous activation of motor units 7 Power Curve 3 b i From Force Velocity FV Curve Power F x V i Power the amount of work that you do per unit time At F 0 P 0 At v 0 P 0 At all others F x V is always positive must have maximum i 25 has optimal power output Stretching active muscle can hold 15x Fo before yielding If you have to move 100 bricks you will be able to get the work done fastest by moving 25 of the load Muscle hypertrophy when you have loads that ate gt than 75 of your maximum i Muscles get hurt when you carry heavy loads of have a discoordination of muscles Lifting lighter loads allows you to i Get your work done faster ii You don t get hurt Muscles can resist more energy than they can generate Lecture 19 Muscle Metabolism and Control 1 Muscle energy Use a b C d m V v V After 20 seconds of running full speed you will slow down Progressive use of energy resources Three ways to get ATP into muscles Phosphocreatine glycolysis oxidative phosphorylation Phosphocreatine PCr 39 Supports about 20 seconds of full activity ii PCr ADP 9 ATP Cr by creatine kinase reaction ATP 9 ADP Pi by myosin ATPase PCR 9 Cr Pi net reaction v Pi inhibits myosin ATPase 1 Need a supply of ATP and removal of inorganic phosphate Have lots of phosphocreatine in muscles all the time viii Having extra creatine can help with pursuit bicycle racing Glycolysis 10 Reactions i 2 minutes of energy use at a high level of activity ii Glucose and glycogen in muscles 9 pyruvate 9 lactate iii No oxygen use iv Because it takes 10 reactions you can t generate as much ATP as quickly but you have longer lasting energy Oxidative Phosphorylation i 2 hours of energy support ii Krebs cycle and electron transport system generating lots of ATP 1 Oxygen used iii Pyruvate 9 CO2 iv Carbohydrate loading increases glycogen storage by up to 30 1 You have enough glycogen for about two hours of activity 2 People have pasta parties to try to increase their glycogen stores before big races doesn t really work v Marathons are 262 miles because that s the distance from the London to Windsor Castle to London 2 Fiber types 5132 Variation in fiber type even within same muscle variation is determined by the neurons Controlled by motor neuron most muscles are mixed Red Fibers i Also called llslow oxidative fibers V V V High mitochondria levels slow myosin 1 ATPase can t run as fast using these muscles but don t use energy as quickly 2 Oxidative because they have high levels of mitochondria and use lots of oxygen quotdark meat High energy capacity low energy use no fatigue Achilles tendon is almost entirely red this is the muscle used to propel self when you walk helps you walk long distances d White Fibers i Also called quotfast glycolytic ii Fast because they have fast myosin ATPase and no mitochondria iii Low energy capacity and high energy use causes them to be easily fatigued 1 Used for sprinting e Can t change these by training what you have is what you have Hypertrophy muscle growth a Two types of growth hyperplasia increase in cells or hypertrophy growth of cells i Skeletal muscle cells can t undergo mitosis ii But they can undergo hypertrophy cell growth b High intensity high force exercise needed for maximum effect c Filament Number i High intensity exercise causes microdamage to filaments 1 Some people believe that soreness is caused a buildup of lactic acid false 2 Disassembly of tangled filaments increased free myosin and causes pain ii Free myosin causes increase in expression of filament forming enzymes more filaments bigger cells 1 Young 48 hour cycle 24 disassembly 24 hour assembly 2 Elderly 72 hour cycle a Risk you have to push your muscles in order to build muscles but high intensity exercise can increase you systolic blood pressure which can be dangerous for elderly could cause a stroke 3 Working out the same muscles every day doesn t make you bigger it just makes you more sore you have to let the healing process occur in order to maximize muscle growth d Testosterone Dependence i Filament production optimized by testosterone ii Females with normal endocrinology cannot maximize muscle size 1 Females who take testosterone will increase their muscle mass Atrophy muscle loss a Reduction in size of muscle fibers NOT loss of number of fibers b Disuse Atrophy i Muscle immobilized which causes a loss of filaments 1 Wearing a cast for several weeks can make the muscle look smaller because they have fewer filaments ii Easily reversible c Denervation Atrophy i Motor neuron damage and causes fiber to lose filament ii Not reversible loss of myotrophic factor from neuron iii Electrical stimulation for paraplegics can decrease rate of atrophy but can t stop it all together Stretch Re ex a Muscle length information b Monosynaptic reflex knee jerk c Activation of afferent neuron produces reflex response d No direct control by upper CNS e Muscle Spindles i Muscle spindles are buried within the muscles are have the stretch receptors ii Groups of intrafusal fibers in connective tissue capsule iii Parallel with skeletal muscles f Intrafusal Fibers iii iv v i Brain needs to know what position muscle is in and if it is moving right now ii Each fiber contains muscle section and stretch receptor section iii Fibers activate afferent neurons from receptor section of fiber iv Nuclear Bag Fibers 1 Have larger central portion of receptors 2 Dynamic Response Only Bag bers a Detects change of length b Highest response when muscle i i inhigiclg39 mai rw l a Detects fiber length b Respects proportion to position slow adaption 6 Gama Motor Fibers a Activate the nuclear bag and nuclear chain fibers b Efferent to intrafusal fibers c Contract muscle portions of intrafusal fibers d Coactivation i Dual activation of alpha and gamma motor neurons ii Alpha motor neurons contracts muscle fibers iii Gamma motor neurons contract intrafusal fibers iv Keep muscle spindles taut 7 Reciprocal Innervation a Inhibition of paired muscle when stretch reflex occurs b Afferent neurons 9 interneuron 9 IPSP to paired alpha motor neuron c Responsible for people pulling muscles while running 8 Golgi Tendon Organ a Muscle force detectors b Receptors in tendon afferent input proportional to muscle force c At very high forces Golgi Tendon Organ sends IPSPs inhibitory to alpha motor neurons i Protective effect Lecture 20 Smooth Muscle 1 Smooth Muscle Structure a Small cells linked by desmosomes b No striations striped appearance in cardiac and skeletal muscles c Filaments parallel but not in register causing no striations d Filaments i Thin filaments actin and tropomyosin no troponin 1 Troponin bound protein in the striated muscle ii Tropomyosin in groove not Am blocking e Dense Bodies i Smooth muscle equivalent to 2 lines ii Anchored to cell membrane also in interior iii Thin filaments attach here and pull ends of cells 2 Tone Only applies to smooth muscle Force with no stimulus Ca leaks in and partially activates smooth muscles Important in blood pressure maintenance holding cavity contents e Strongest muscle in body is smooth muscle 3 Smooth Muscle Contraction 90 Tm VVVV Different control mechanism than striated muscle Ca also activates Calcium Sources i Most through channels across cell membrane ii Some small ST released by P3 Myosin light chain Kinase i Ca activated ii Adds phosphate to myosin light chains iii Activate myosin ATPase for shortening and force 1 Kinase are enzymes that add phosphate to something iv Phosphorylation of a light chain causes the shortening of a smooth muscle and contraction 1 As long as there s Ca the light chain stays on Force Generation i MyosinADPPi with MLCP binds actin ADP and Pi leave ii Myosin twists generates force iii Filaments slide to reduce force iv This part similar to striated muscle Myosin Light Chain Phosphatase i MLCPase removes phosphate from myosin light chains Latch a Removal of Pi from light chain when actin myosin attached decreases myosin detachment rate b Maintains force with little energy use c Allows BP maintenance with low energy use allows upright position Smooth Muscle Types a Vary with function emptying cavities or maintaining force b Visceral Single Unit Smooth Muscle i One contracts 9 all contract ii Use AP s linked by gap junctions Phasic activity stomach Random contractions small intestines 1 Action potentials go up and down depending on what channels happen to be open v Must shorten to empty cavity Neural Effect 1 Parasympathetic release Ach cause contraction 2 Sympathetic release NE cause relaxation MultiUnit SM i Each cell is individually active no APs or gap junctions ii Get average force large blood vessels eye muscles iii Tone 1 Very important 2 Allows you to maintain the contractions using small amounts of energy 3 Small force with latch low energy cost to maintain BP 4 Force can go up for down from tone level iv Neural Effects 1 Sympathetic receptor dependent a Alpha open Ca channels increase contraction b Beta 2 increase Ca pump activity 352 D V m V n V n V PSL 250 Lecture 21 Cardiac Structure and Activation 1 Cardiac Muscle Structure a Cylindrical shaped cells b ntercalated disks join cells endtoend c Filaments as in skeletal muscle V V d Thin filaments activation by Ca binding to Troponin i All muscles are activated by Ca e Intercalated Disks i Creates uniform pumping 1 Will not get an efficient delivery of blood if cells don t beat consistentlyat the same time Junction where two cardiac muscle cells reach one another Strong desmosome connections between cells 1 Heart starts beating at 5 weeks desmosomes are responsible for holding the heart together 2 Desmosome deficiency would create a miscarriage iv Gap junctions efficiently deliver blood to lungs or heart tissues Circulatory Flow Circuit a Heart pumps blood in a double circuit i Left and right sides are linked but they are different channels b System Left ventricle 9 aorta 9 body 9 vena cava 9 right atrium c Pul Right atrium 9 pulmonary artery 9 lungs 9 pulmonary vein 9 Left atrium d Heart attacks occur when the heart muscles don t have enough energy to do their work i Most occur on the left side of the heart because the left side requires 5x s more energy than the right side e Lowest average blood pressure 20 year old women i Women s health is better overall because of the positive effects of estrogen on their circulatory system f Average blood pressure of 12080 at highest when pumping and lowest when filling up g Blood pressure in vena cava can be below zero because inhaling creates a negative pressure in heart cavity h Four valves maintain direction flow one direction only i When pressure is greater behind the valve it opens ii When pressure is greater in front of the valve it closes 1 When pressure is greater in front of the valve it does not open in the opposite direction it is a oneway valve Cardiac Activation Structures a Activation pathway has autorythmic cells b Atria i Site of normal heartbeat initiation ii Average person has 75 beats per minute iii SA Node 1 Where the heart starts it s beat in the right atrium 2 Depolarizes to threshold starts AP 3 Fastest depolarizer no stable baseline membrane potential 4 The intermodal pathway connects the SA Node to the atrium ventricle node 5 Premature beats occur if the heartbeat starts elsewhere not usually harmful a Sign that heart can selfcorrect itself if you can have premature beats and then get back to normal iv Atrial muscle 1 Right atrium activated by SA node spreads toward the left atrium using the interatrial pathway 2 Spread through gap junctions 3 Atrial muscle and ventricle muscle are NOT auto rhythmic contraction spreads downward 4 There is a lot of passive blood that flows so if the atrial muscle stopped working you would be fine Atrium Ventricle Node i Electrical connection from atria to ventricles ii Delays AP spread allows ventricular filling to be completed 1 May cause an AV block AV block produces separate atrial and ventricular activation Ventricles i AP enters septum first 9 spreads to apex 9 up to the ventricular muscle ii Ventricular muscle contraction spreads upward iii Bundle of His 1 Autorhythmic 2 Off of AV node down the septum C V d V in V on V iv Purkinje Fibers 1 Branch off of Bundle of His down to the apex then to the ventricular muscle 2 Activated by Bundle of His through gap junctions v Ventricular Muscle 1 80 total volume of cells Apex cells activated first by Purkinje fibers then muscle celltocell through gap junctions 2 Contraction spreads upward forcing blood into the aorta and pulmonary artery 3 No pacemaker activity Pacemaker cells a Autorythmic no stable baseline potential b SA and AV nodes some cells of B of H and Purkinje fibers Depolarization a Na energy to threshold b Opening of Ca channels during AP c Opening of K channels during repolarization d Little Na influence on AP e Neural Influences i Sympathetic neurons increases depolarization 1 NE opens Ca channels in atria and ventricles 2 Increases heart rate and strength of contraction ii Parasympathetic neurons vagus n Ach decreases depolarization rate 1 Ach decreases Ca channel opening in atria 2 Decreases heart rate Electrocardiogram diagram a Sum of changes in cardiac APs b Relation to cardiac AP i Detects changes in the sum of APs ii Measures changes in membrane potential detected by difference distances to lead 1 Produces a PWave c Ventricular Fibrillation i Life threatening no coordinated emptying no blood delivery ii Need electrical shock to recoordinate APs PWave a Atrialdepolarization b Start of atrial contraction QRS complex Ventricular depolarization masks atrial repolarization End of atrial contraction start of atrial filling Sta rt of ventricular contraction Distance time between the PWave and the QRS Complex tells you how long the atria are contracting for Distance time between the QRS Complex and the TWave tells you how long the ventricles are contracting for Distance time between the TWave and the QRS Complex tells you how long the ventricles are filling up for TWave a Indicates ventricular repolarization b End of ventricular contraction start of ventricular filling m agggz PSL 250 Lecture 22 Cardiac Pumping 1 Cardiac Cycle Sequence of contraction and relaxation 4valves 2 between the atrium and the ventricle aorticpulmonary keep blood flow one way Diastole i Relaxes heart 352 2 U V ii Time for filling iii End diastolic volume 130 ml iv When blood flows v No air in the circulatory system absence of air means that the relaxation of the heart siphons the blood into the ventricles Atrial Systole i Atria contract first ii Completes filling of ventricles iii Fill up most of ventricle by having blood flow passively iv Only the last 20 of the filling occurs because of the atrial systole Ventricular Systole i Follows atrial contraction ii Contraction spreads upward iii Pressure must be greater in the ventricle than aorta to open aortic valve iv Aortic pressure 1 Left ventricular pressure must be greater than 2 Load left ventricle works against 3 High BP puts greater load on heart a Lower number diastolic pressure in the blood pressure is more important because it tells you how hard your heart have to work Ejected Blood Volume i quot 7090 ml of blood ejectedbeat ii quot 65 of end diastolic volume 1 Heart is never fully empty iii Lower resting heart rate means higher ejected volume than 65 means it s more efficient at delivering blood iv Heart Rate Dependence 1 The maximum heart rate is 220 you age a 220 20 years old maximum heart rate of 200 beats per minute b 220 63 years old 157 2 Rates above 180 decrease filling time a Must be motivated to exceed 180 b This can decrease cardiac output c Potentially life threatening Arterial Pulse a Arterial walls expand to hold blood b Rebounds during diastole creates pulse i Blood only flows during diastole c Little drop in blood pressure throughout arteries d Arm falls asleep because you are pressing on a vein you shake your arm to get blood moving through your arm Heart Sounds a Closing of valves turbulent blood flow creates sound i When blood flow is smooth you don t hear it b Low pressure AV mitrial and tricuspid valves close first then high pressure aortic and pulmonary valves c Different sound intensities d Murmurs i Nonlaminar nonsmooth flow 9 sound when valves should be closed 1 Turbulent flow can be heard ii Murmur because the valve isn t closing properly 1 Blood is squirting through when it shouldn t be iii Valve stenosis 1 Heart valve is stiff doesn t properly open or close 2 Stillvalve small opening 9 V m V v V 4 3 Turbulent flow as blood squirts through iv Valve insuf ciency 1 Valve leaves don t properly mesh and leave space in between that blood can leaks through a Low frequency sound 2 Children with improper valve closure sometimes outgrow this murmur as growth alters valve alignment 3 May sometimes need a valve replacement a Use genetically modified pigs Cardiac Output a Amount of blood pumped liters per minute i Normally 5 liters of bloodminute b Stroke Volume x Heart Rate C0 i quot 70 ml at 70 beats per minute quot 5 L blood min ii Body has about 5 L of blood iii Circulation time 1 minute c If you are really athletic you will have a higher cardiac output per beat d Starling s Law i Stroke volume control ii Increase in venous return stretches cardiac muscle 9 increase in force 9 increase in CO More actinmyosin interaction less thick 2 line contact less thinthin overlap more Ca release Stronger contraction more Stroke volume how much blood in heart more Cardiac Output amount of blood pumped stroke volume x heart rate v Diastolic volume how much blood is in the heart before it pumps the fullest the heart can be 1 Heart never completely empties e Neural influences i Both SV and HR changes ii Parasympathetic 1 Dominant at rest 2 Reduce your heart rate and reduce your cardiac output 3 Cut vagus nerve to heart HR increases from 70 to 100 immend 4 Exercise increases parasympathetic output decreases resting heart rate a May go to 30 s or 40 s Sympathetic 1 Increased Ca channel opening a Faster depolarization towards threshold causes increased HR b More Ca causes more force causes increased SV iii PSL 250 Lecture 23 Arteries and Arterioles 1 Blood Vessels a Three layers endothelium vascular smooth muscle connective tissue i Capillaries only have endothelium b Types of Blood Vessels i Arteries arterioles capillaries veins ii Each has a different function iii Lymph vessels carry excess filtered fluid very small amount 1 Cardiac output it 5 Lminute 2 Flow in lymph system is 1 mLminute c Aneurism when the blood breaks through the first two layers but not the third of connective tissue i If less than 2cm in size then doctors won t touch it Physical factors Some factors constant such as vessel length other factors variable such as vessel radius because it s always partially contracted Flow pressureresistance Ex Vessel 2 is two times wider than vessel 1 235 6 V V V Resistance in vessel 2 116 of Vessel 1 Flow in Vessel 2 16 times of Vessel 1 Resistance 1rquot4 iv Flow rquott Vessel radius i Most important variable factor ii Resistance quot 1radiusquot4 1 Small constriction causes large increase in resistance decrease in flow 2 Small dilation causes large decrease in resistance increase in flow 3 Short blockages can compensate with increased velocity until greater than 80 closed 4 Brain always gets a constant blood flow Viscosity i Thickness of blood ii Controlled by hematocrit red blood cells in blood 45 males 42 females need large change to influence blood flow iii Above about 48 red blood cell interaction with arteriole walls greatly increases resistance Arterial conductance Arteries are conductance vessels they conduct blood around the system High pressure blood enters aorta at 93 mm Hg Large arteries expand to hold blood little change in blood pressure 24 mm wide Momentum of moving blood carries blood forward to tissues Aorta is the same size of your thumb Arterial pressure i Systolic pressure highest pressure in system is 120 mm Hg diastolic pressure lowest pressure in your system is 80 mmHg Pulse pressure is systolic diastolic 120 80 40 mm Hg Mean arterial pressure diastolic 13 Pulse Pressure 80 1340 93mmH Coronary Circulation a Heart rate dependent i When a muscle is going through systole the veins are squeezed shut b Decrease diastole at high heart rate 9 decrease in filling time and decrease in coronary flow c Coronary flow only occurs during diastole cl f Heart rate gt 180 decreases cardiac output potential heart failure Atherosclerosis a Multiple stages i Stage 1 LDL low density lipoproteins lays down fatty streak 1 LDL is only bad cholesterol when you have unlimited food 2 In places where there is starvation this is good cholesterol because it means you had enough to eat ii Stage 2 WBCs and fibroblasts overgrow fatty streak iii Stage 3 calcium infiltration hardens overgrowth 1 hardening of arteries Alcohol effect i Reverses the stage 1 from above ii Modest alcohol consumption can reverse stage 1 atherosclerosis 1 One drink per day 2 Prevents colon cancer lowers blood pressure iii Has a biophysical effect not a receptor effect iv No alcohol effect on other stages Arteriolar ow Arterioles branch off arteries 30 microns wide pressure is 93mmHg at artery end Carries blood flow to capillaries pressure is only 37mmHg capillary end i Lost over half of pressure gradient this is the control site Arteriole can go in either direction m V n V 33 E 039 V m I 7 Tone V a b Keeps blood vessels partially dilated so you can relax or contract more easily Partial activation with no stimulus Perfusion control a E I amp Sympathetic neurons i Alpha receptors cause calcium to go up ii beta 2 receptors causes them to relax Metabolites i Adenosine is a metabolite that controls local blood flow and causes them to relax ii Whichever tissues in the body that work the hardest get the most blood Paracrine control arteriole smooth muscle BE i Nitric oxide causes the relaxation of muscles All can work simultaneously PSL Lecture 24 Capillaries Lymph Veins 1 Capillary Blood Flow N m Capillaries are smallest blood vessels and you have lots of them b No cell in the body is more than 2 cells widths away from a capillary i Many capillaries spread flow out and speed c Blood flowing through aorta has a high speed associated with it d Red blood cells are a little bigger than capillaries so they have to be squeezed through very slow flow e Smallest in your brain very tight f Capillary Pressure i 37mmHG at arteriolar end and then goes down to l7mmHg at venous end ii Process of pressure falling is important for the exchange of material g Capillary Fluid Exchange i Balance of BP forcing fluid out and osmotic pressure from plasma proteins drawing fluid in ii Proteins are too big to draw through pores and needs vesicles slow process iii Fluid moves through capillary pores iv Filtration 1 Moving out 2 Dominates at high pressure end arteriolar v Reabsorption 1 At venous end lower BP BP lt Osmotic pressure 2 Fluid reenters 3 Net 37 out and 36 in fluid sweeps volume around capillary a Slightly more fluid filtered outward than reabsorbed inward Lymph Flow a Return of excess filtered fluid to circulation b Lymph vessels all over body start at the tissue c Highway that bacteria and metastatic cancer spreads d Return of Filtered Fluid Fluid enters closed ended lymph vessels Large lymph vessels have valves 1 Made up of endothelial cells that overlap and create the valves 2 If pressure is higher on outside then fluid is forced into lymph vessel 3 If the pressure is higher inside then the fluid squeezes the edges closed and the liquid can t leak out Lymph nodes are sites of large lymph vessel merger 1 Under neck and arms Vena cava pressure can be 0 or negative 5milmin when you draw air in lymph enters the vena cava BP 0 at thoracic duct in chest 1 7200 litersday Edema i Swelling such as from a broken nose ii Many reasons why 1 Excess filtration broken capillaries causes lack of protein gradient 2 Low blood pressure starvationalcoholism causes lack of protein gradient a Children with distended bellies because they have little protein in their diets that they can t keep the fluid in their blood stream 3 Bacteria presence and destruction draws fluid osmotically 4 Parasites filarisis block lymph flow fatal a Elephantitis 3 Venous Flow a Capacitance vessels i 23 of total blood volume ii Holds large volume of blood veins b Under very low pressure c Venous Pressure i 17mm Hg at capillary end to 0mm Hg at vena cava ii During inspiration breathing in creates a negative pressure iii BP needs help getting blood up to heart d Venous Valves i Prevents backflow ii Every 12 inches in large veins iii Valve can be demonstrated on veins on back of hand e Skeletal Pump i Muscle contraction squeezes veins forces heart to start 1 Contraction makes veins shorter and wider f Varicose Veins i Ruptured valves column of blood slow return comes from standing around 1 Contraction forces blood back to heart and prevents clotting Breaking one valve forces the valve next to it to hold two columns of blood and can lead to breaking Clots may forms 1 Coroneted artery could cause heart attack 2 Internal corrated could cause stroke or face to fall asleep 3 Big toe could cause toe falls asleep Blood bypasses varicosities through other veins Deep vein thrombosis dangerous 53 PSL 250 Lecture 25 Red Blood Cells amp Platelets 1 Plasma 1 Serum yellowish liquid portion of the blood without clotting proteins b Plasma Liquid portion of blood with clotting proteins i Mostly water electrolytes metabolites hormones proteins Plasma Proteins i Albumin highest amount draws fluid into capillaries binds hydrophobic hormones 1 Largest amount of plasma proteins ii Globulins many subgroups gamma globulins are ANTIBODIES iii Fibrinogen final protein for blood clot formation mesh that makes the blood cot Erythrocytes Red Blood Cells RBCs carry oxygen and C02 Produced in bone marrow expensive Limited life time RBCs have NO nucleus and NO organelles i Only a sack full of hemoglobin Hb n V 1 35 U V e Kidneys clean blood so there is a lot of blood flow i Erythropoietin tells kidneys to make more blood f Production i In bone marrow from stem cells ii 20 ml of RBCsday 150ml bloodday iii Low blood 0 causes release of EPO from kidneys when 0 levels low produce more live for 120 days and gets significantly stiffer g Shape i Bioconcave disks ii 8 microns across iii Spectin is the net under membrane helps maintain shape h Destruction i RBC membrane lose cholesterol over time which causes them to become stiff ii Rupture in spleen capillaries at 120 days iii If spleen lost liver ruptures RBCs Hemoglobin a Four protein chains i FE2 b Adult 2 alpha and 2 beta chains i Each subunit has protein globin with a hemen group in the center ii iii Oxygen binds to the iron atom iv Cooperatively increase bindings at lungs and release tissues Fetal 2 alpha and 2 gamma chains i Higher affinity for oxygen than adult hemoglobin ii Draws oxygen from maternal blood iii Replaced by 23 months postnatal d Anemia i Lack of oxygen altitude ii Reduced RBCs bleeding no anemia with menses 50ml5days iii Reduced delivery circulatory iv Reduced use cyanide stops oxidative phosphorylation no ATP v Sickle Cell Anemia 1 Single hemoglobin mutation 2 Low oxygen 9 hemoglobin forms stacks and changes cell shapes 3 Sickles cells hang up on branch points 4 Survival value protection from malaria a Parasites lay eggs in RBCs b Growing malaria parasites rupture weekend RBC membranes before maturity vi Iron De ciency 1 Lack of iron decreases amount of hemoglobin 2 Not from using noniron cookware wrong form of iron in cookware Each hemen has an iron atom at its center 0 4 Platelets a Pinched off parts of megakaryocytes in bone marrow b Production i Megakaryocytes stay in bone marrow ii Platelets pinch off and enter circulation iii Spleen kidneys and liver make thrombopoitin ThrP iv ThrP stimulates platelet formation v ThrP binds to platelets in blood when platelets low 9 increase free ThrP c Activation i Activated by collagen and other proteins in connective tissue of blood vessels ii Platelets adhere increase ADP release more P s come and stick iii Make platelet plug Hemostasis U39I V a Stoppage of bleeding b Vasoconstriction i Decreased BP at site of cut tone constricts small vessels c Platelet Plug i Exposure of collagen 9 platelet sticking 9 ADP positive feedback ii Prostacyclin from healthy blood vessels blocks platelet adherence 1 Prevents platelets from sticking on healthy tissue and prevents platelet plugs d Coagulation i Blood clotting 2 systems ii Both lead to fibrinogen soluble 9 fibrin selfadhering iii Fibrin form mesh that traps RBCs and forms blood clot iv Broken blood vessel v Intrinsic System 1 Inside plasma collagen activates 2 Cascade needs Ca and all factors in pathways vi Extrinsic system 1 Requires damage to occur that causes the release of thromboplastin 2 Thromboplastin from damaged tissue starts cascade 3 Merges with intrinsic system halfway down 4 Responsible for most clot formation 5 Hemophiliacs lack the intrinsic system and have to survive on a clotting system that works on the extrinsic system a If they get a sharp cut then have to induce trauma in order to activate extrinsic system e Clot Removal i Plasminogen trapped in clot 9 cascade started by collagen 9 plasmin ii Plasmin is an enzyme that slowly dissolves a clot over 2 weeks PSL 250 Lecture 26 White Blood Cells amp Innate Immunity 1 Cell Types a Leukocytes b 5 types of white blood cells all have different defense functions i Multilobed nuclei ganulocytes neutrophils eosinophils basophils 1 Stained by neutral acid and basic dyes 39 and 39 ii Singlelobed nuclei 0 39 2 Phagocytes a Phagocytosis of bacteria and dead cells i Phagocytosis surrounding and digestion of material that is recycled by cells Order of attack resident macrophages neutrophils new monocyte 9 macrophage migration Neutrophils i Rapid response move from blood to damaged tissue ii Diapedesis squeeze through capillary pores that are smaller than they are attack bacteria 1 llmoving your foot through Monocytes amp Macrophages 25 D V i Monocytes are small cells that move into tissue and become macrophages ii Resident macrophages wait for bacteria to come iii During infection vast movement of monocytes into infected area 1 This is puss white because white blood cells are a major component of it 2 Responsible for killing infective agent killing and ingesting it iv Massive macrophages attack on bacteria 3 Eosinophils a Produce acids that kill parasites b High in digestive tract skin reproductive tract c Produce allergic responses 4 Basophils a Release histamine b Histamine causes inflammation i Increase blood flow arteriolar dilation 1 Antihistamines blocks the effect so you can breathe easier ii Increase pore size allow diapedesis c Stained by basic dyes 5 Defense Mechanisms a Innate nonspecific immunity defense mechanisms not influenced by prior exposure b Acquire specific immunity B and T lymphocytes attack specific antigens 6 In ammation swelling a Nonspecific response occurs with any inflection or injury b Chemotaxis i Chemical signals from damaged areas draw phagocytes ii Highest concentration near damage c Complement System i Series of 9 plasma factors C1C9 ii Major bacterial killer iii Activation 1 By antibodies or by the protein porperin 2 This is opsonin tags of surface carbohydrates on bacteria 3 Leads to pore formation in bacteria membranes iv Pore Formation 1 C5C9 can form pores in membrane 2 Very local rapid inactivation a Kills the bacteria but not your tissues next door 3 Pore allows osmotic lysis Na enters H20 follows cell swells and bursts 4 III feeling cause bacterial toxins activation of pain receptors from partially digested protein of dead bacteria Histamine 1 Increase blood flow brings phagocytes oxygen amino acids 2 Increase capillary permeability opens pores for liquid and diapedesis 3 Not responsible for sweating increase or big changes in blood flow 7 Interferon a Cytokine released from virusinfected cells b Binds to the cells next door and stops cells next door from making new proteins stops protein synthesis c Activated antiviral defenses in cells near virus infected cells d Many side effects e most expensive drug there is 8 Natural Killer Cells lt V a NonT lymphocytes b Bind to cells and inject perforin molecules into the cell killing the cells c May kill off donor organ cells if it is not a good match d No prior exposure needed for activation e Activation i Lipids and carbs on bacteria tumors transplants and by antibodies on cell surfaces ii Forms pores by injecting perforin kills by lysis PSL 250 Lecture 27 Adaptive Immunity B Lymphocytes 1 Antigens N U a Come into the body as a foreign object b BCells and TCells destroy c Selfantigens cause autoimmune disease i B or T cells will misdirect and attack something in own body d Statistically autoimmune A1 diseases are more common because people live longer e Antigen Presentation i Antigen is introduced to B and T cells by partially digested macrophage 1 Part of molecule linked to hi protein and linked to cell 9 B and T cells come into contact with macrophage ii B or T forms around and produces system that attacks it B Lymphocytes B Cells a B and T fully mature by passing through lymph system b Binds antigens in liquid plasma and to surface of cell c B Cell clones produced to target antigen d Plasma Cells i Constitute most of the Bcell clones ii Become antibody protein factories iii ER takes over other organelles short life 1 Only live for a week but they produce MANY antibodies iv Manufacture and support antibodies e Memory Cells i Constitute some of the Bcell clones ii Live for years so in future ifantigen is present it will bypass presentation and produce plasma cells to have huge response secondary iii Measles shot only need it once iv Tetanus shot need it every 10 years v Can t get a shot for the common cold because it mutates so quickly f Primary Response i First contact with antigens ii Slow short weak g Secondary Response i When Bcells are prepared for antigen ii Fast long strong Immunoglobulins Antibodies a 5 Categories IGG IGA IGE IGD IGM all Yshaped b Have more IGG than anything else smallest every secretion has IGG i Present in breast milk for the first week and provides immunity to the newborn ii Nonspecific response Antibody Functions i Activate the Complement system cascade of C1C9 IGG attack bacteria 391 V h V 1 Different categories activated different systems 2 Different antibodies will attack cell ii Activate phagocytes iii Activation of natural killer cells iv Pregnancy test when a woman is pregnant she makes more HCG protein which shows up in the urine 1 Antibody in test kit binds to the protein and creates a color reaction Blood Types a Produce enzymes that add carbs onto red blood cells b Gene codes for enzymes c If given a mismatch of blood your blood forms a glutination and causes the cells to stick together can kill you d A A Carbohydrate e B B Carbohydrate f AB Both A and B Carbohydrate g 0 No carbohydrates h Rh or codes as well for the addition of a carbohydrate ABO System a A Carb b B Carb c O No Carb Rh Factor a or b Can change because of activator c Rh mothers of Rh children if there is mixture of blood during birth would produce primary response d Then second child would produce secondary response killing mom and child i Rogam shots PSL 250 Lecture 28 Adaptive Immunity T Lymphocytes amp Skin 1 T Lymphocytes Protect you against viruses and cancerous cells m b Attack cells with both a foreign antigen and selfantigen M HC c Cancer virus infected cells transplants attacked d Cytotoxic T Cells i Bind to cell and inject perforin and forms pores 1 Pore gets larger until it can kill viral infection target cell ii Osmotic lysis follows 1 Killer cell e Helper T Cells i Release cytokines paracrinelocal hormones that activate all B and T lymphocytes 1 Most common 2 Activates immunize system beefup all the immune activity 3 Stimulates antibody formation and blood flow ii Site ofattack for HIV f A DS i HIV attack on helper T cells decreased immune response ii Opportunistic diseases can now attack Avoid multiple concurrent infections 1 The immune system can only handle so much at once so when many infections occur at once it overwhelms the system HIV needs broken skin to enter hard to get HIV cannot cross through healthy skin 1 Receptive anal intercourse 3 2 Needle 3 Broken skin in vagina or penis 2 Helper T Cell Cytokines 5 In an I V V a Paracrine that regulate immune response b Increase proliferation growth and function c When cytokine structure known renamed and interlevkin Major Histocompatibility Complex a Previously known as HLA antigens i MHC Cass 1 1 Identical for transplants 2 Selfantigens on surface of all cells 3 Identify cells as self 4 36 out of 100 possible formations on every cells a In most people m w v u b Most likely to get exact match to sibling rather than parents unless parents are closely related 5 Others in foreign cells attacked MHC Class 2 1 Inject and present antigens activate T cells Transplants a Nonmatching MHC 1 are attacked by antibodies b Partial match has both selfand foreign antigen triggeringT lymphocytes attack c Try to match Cell 1 proteins d T cells may attack suppress T cells more infections e Leukemia cancer of the bone marrow which exports immature white blood cells i Need to replace marrow which can have a risk of fungus ii No marrow 9 no immune system iii Fungus can thrive Tumors a Benign tumors stay localized i May cut off blood supply so nearby tissues ii Sometimes they aren t cancerous b Malignant tumors have transformed cells i Cancerous ii Can infiltrate nearby tissues iii Can metastasize to other parts of the body iv Use lymphatic system as mode of transport c You are lucky if you get a new protein there Allergies a Immune reaction to a harmless substance b The body s response is what s most important Allergens can produce responses Immediate Hypersensitivity a Immune response in 20 minutes i Secondary responses are fast and strong if they have been exposed to the allergen in the past then they will get the secondary response b If the reaction turns on in minutes then it is B cell mediated antibody production i Stimulate histamine release ii Constrict airways in lungs c Stimuli i Nonbacterial pollen bee stings penicillin mold dust IGE antibodies ii Skin eyes lungs digestive tract reproductive tract has a lot of IGE antibodies designed to attack parasitic worms iii Chemical triggers histamine vasodilation and capillary 1 Permeability increase 00 V 9 2 SRS4 strong a Bronchiole contraction potentially lethal d Symptoms i Localized reaction 1 Upper respiratory hay fever congestion edema sneezing running nose ii Bronchioles asthma inflammation constriction increased mucus difficulty breathing e Anaphylactic Shock i Allergens spread by blood ii Bronchoconstriction 1 Treat with epinephrine iii Shock low blood pressure 1 Also caused by bacterial infections 2 Severe hypotension low blood pressure due to increased capillary permeability Delayed Hypersensitivity a Breaks skin barrier gets to blood calls T cells to area b Immune response in 24 hours c T cells mediation d Poison ivy some toxins stimulate e Tcells migrate to area of contact and produce rash Skin a Mechanical barrier with defense mechanisms b Different layers i Men have 13 layers which is what makes it more course c Epidermis i Layers of epithelial cells ii Dead cells outermost with dividing cell beneath iii No blood supply supplied by diffusion from dermis iv Desmosomes and keratin fibers hold cells together with keratinized layer remaining after death v Pathogen tight airtight fairly waterright prevents evaporation 1 Nothing can pass unless there is a cut vi Burns destroy epidermis cause hypertension and shock vii Lose sufficient water volume causes BP to fall with burns d Dermis i Connective tissue beneath the epidermis ii Blood vessels loaded with nerve endings many cell types 1 Blood regulates heat loss 2 Sweat gland sweat has variable Na content 3 Sebaceous glands oil waterproof skins 4 Hair follicles increase touch sensitivity 5 Melanin absorbs UV lights UV sensitivity iii N Nitroso Nicatine NNN causes you to have a cancer e Hypodermis i Fat cells ii Separator between the body s core and the shell PSL 250 Lecture 29 Lung Structure amp Breathing 1 2 External Respiration a Exchange of gasses 02 and C02 between body and environment b Internal respiration use of 02 by mitochondria NonRespiratory Lung Functions a Water and heat loss i Water is going from gaseous state to a liquid state when you breath out hot air into cold air ii Because you can see it it means its cooling off U V b Increases venous return acidbase balance speech pathogen defense circulatory modification ACE sense of smell Lung Structure 3 b C d Left and right lungs are separated by strong membranes i Good if you have a collapsed lung because the other lung is in a separate compartment Trachea 9 bronchi 9 bronchioles 9 alveoli gt 20 generations of bronchioles Alveoli are air sacs sites of gas exchange i Has 2 Types of Cells ii Type 1 Cells 1 Makes up most of the alveoli 2 epithelial cells 1 micron think 3 Separate air from the interstitial fluid 4 Allows gas to pass across the alveoli wall iii Type 2 cells 1 in alveoli produce surfactant 2 Reduce resistance to alveolar opening Lung Mechanics avg m V v V Uh V 339 V Air flows from high pressure to low pressure Lungs are surrounded by plural sac There is a continuous pathway of you removing water from the lungs which comes from the plural sac i Loss of water creates a slight decrease in pressure in the plural sac ii Pressure outside of lungs is always lower than the pressure inside the lungs Atmospheric IntraAlveolar Interpleural Pressures i A 760mmHg at sea level 600mm Hg at Denver 1 mile up ii IA variable exhale 12gtatm inhale l2ltatm iii IP between lungs and the thoratic wall 1 Always 4mmHgltatm 2 Lower pressure keeps lungs always inflated Boyle39s Law i Pressure x Volume Constant ii Decrease V 9 Increase in P iii Increase V 9 Decrease in P Tidal Volume i Tidal volume is the normal breathing volume ii Inspiratory reserve volume extra amount you can inspire 1 By taking a deep breath before diving into a pool iii Expiratory reserve volume extra amount you can expire 1 Exhaling extra air playing the trumpet Inspiration i Pressure must be less than atmospheric ii Regular phrenic nerve from medulla sends AP to diaphragm causes diaphragm to contract iii Diaphragm contraction um quot 39 remember Boyle s Law iv Decreased pressure causes inspiration v Extra inspiration 1 eternal intercostal muscles contract expand thorax Expiration i Normally passive you don t have to do anything just stop activating your muscles ii As diaphragm relaxes will iii Extra expiration 1 internal intercostal muscles between ribs contract 2 Abdominal muscles contract also 3 Squeeze thorax in V on V i Compliance i Ease of lung expansion ii Normally easy to inflate are very compliant easy to open up iii Increase fibrosis asbestosis of lungs decrease compliance Alveolar surface tension a Adherence of H20 molecules creates surface tension on the inside of alveoli i Negative charge on the hydrogen positive charge on the oxygen b Surface tension must be cover come to open alveoli c Surfactant i Several phospholipids mix with water and decrease surface tension ii Also prevent edema in lungs iii Surfactant is first made at 36 h week of gestation 1 So that when you re born you can easily inflate your lungs iv Glucocorticoids a shot increases surfactant production in premature infants Anatomical dead space a Normal tidal volume is 500ml b 150ml of mouth pharynx trachea bronchi and bronchioles is dead space c 350ml is normal alveolar inflation d Long slow breathing minimizes dead space effect e Short rapid breathing still must fill 150ml of dead space PSL 250 Lecture 30 Gas Exchange 1 U V b V Partial Pressures Go from high to low Gas equivalent to concentration Sea level 760mm Hg 600 N2 160 02 C02 3mmHg Gases independent of one another one gas may move in while another moves out Air in lungs is water saturated Alveolar Air 1 agggz a Partial pressure of 02 100mmHg Partial pressure of C02 40mm Hg b Venous blood Partial pressure of 02 40 Partial pressure of C02 46mm Hg i Venous blood is the blood that arrives at the lungs Diffusion Across Alveolar Wall a Gases follow partial pressure gradients b Capillary gasses match tissue it goes through c 0202 enters pulmonary capillaries until P02 is 100mmHg d C02 C02 leaves pulmonary capillaries until PC02 is 40mm Hg Pulmonary Circulation a Left side of the heart works harder and is more likely to have a heart attack b Lower BP then aorta c 1520mm Hg arterial pressure of pulmonary artery d VentilationPerfusion Ratio i Match of what parts of the lung have open alveoli and where the blood in lungs is going 1 Usually only use 10 of lungs Ventilation and perfusion normally well matched 8 Areas that have open alveoli get more blood flow iv As need for gas exchange increases both blood flow and ventilation increase in new lung areas Tissue Gas Exchange 1 Reverse of lungs b Oxygen has to leave the blood stream and move out to the tissues c Need a gradient that allows the oxygen to move from high to low pressure d 02100mmHg arterial blood loses 02 to 40mm Hg tissue until capillary is 40mm Hg i Capillary is a lower volume so it comes to an equilibrium when the capillary matches the surrounding tissue Oxygen Transport a 15 carried by dissolved 02 b 985 carried by binding to hemoglobin c OxygenHemoglobin Binding i Sigmoid curve cooperative between 4Hb subunits ii When oxygen binds to hemoglobin it no longer contributes to partial pressure 1 Allows you to transport more oxygen iii Four oxygen binding sites on every hemoglobin iv Steep Region 1 At tissues fall in P02 unloads 02 2 Below 60mm Hg 3 Tissues have an average of 40mm Hg v Plateau Region 1 Occurs for anything above about 60mm Hg this is fully saturated 2 At lungs all Hb is 02 bound no effect of extra 02 3 At lower P02 even more 02 delivery 4 quotwork hard get oxygen vi Bohr effect 1 C02 and acid shift in Hb02 curve to the right 2 More 02 unloading at give P02 vii Carbon Monoxide 1 2 effects a Binds HB 200x stronger than 02 less 02 available i Never dissociates must lyse red blood cells to lose C0 b Shifts Hb02 curve to left less 02 delivery d Hypoxia i Low blood 02 ii Low 02 air high altitude or 02 deprivation iii High altitude ethnic groups higher Hb even at sea level iv Sea level ethnic groups low 02 training increases Hb lose when return to sea level e Hyperoxia i Breath high 02 ii No addition Hb binding already full iii Increased dissolved 02 may decrease breathing rate benefit is only psychological Carbon Dioxide Transport a 935 V V m V 10 dissolved 30 bound to plasma protein and Hb i C02 is more soluble in water than oxygen 60 converted to bicarbonate by carbonic anhydrase CA CA catalyzes H20 C02 9 H2C03 9 HC03 H Carbonic Anhydrase i In red blood cells ii Converts C02 9 bicarbonate at tissues as C02 is added iii At lungs reversal bicarbonate 9 C02 then breathed out Hypocapnia i Low C02 ii Hyperventilation decrease C02 in blood 9 faint 1 Hyperventilate when under psychological stress iii Breathing into bag C02 increases back to normal Hypercapnia i High C02 ii Increased breathing rate iii Increase C02 in blood strongest stimulus for increased respiration v V PSL 250 Lecture 31 Regulation of Respiration 8t Lung Diseases 1 N V U V In V Medullary Control Centers a Dorsal respiratory group DRG rhythmic discharge 9 phrenic nerve 9 diaphragm i Initiates normal breathing b Ventral respiratory group VRG causes increase inspiration and expiration Pontine Control Centers a Modify medullary centers b Pneumotaxic center switches off inspiration c Dying of whiplash head moves to far forward and tears the brainstem d Dying of broken neck head moves back and crushes the brainstem e Apneustic center prolongs inspiration normally inhibited i If PC damaged Hering Breuer reflex from lungs stops inspiration ii Apneustic breathing deep breath in short breath out Nothing to stop inspiration Chemical Control of Respiration a Most powerful controller of rate b Increases blood C02 9 increases brain C02 9 increase H and HC03 c H in the brain increases DRG rate d Peripheral Changes i In carotid bodies and aortic bodies ii Increase H or increase C02 or decrease 02 will increase rate of respiration iii Little effect in normal range iv P02 lt 60mmHg increases rate no helping in C0 poisoning Sleep Apnea a Means llnot breathing during sleep b Happens when you sleep on your back c Uvula and soft tissues in pharynx close of the trachea d Decreased DRG activity or airway obstruction e In REM pharyngeal muscles relax and tongue blocks trachea f Decreases restful sleep 3 SIDS i Similar to sleep apnea ii Sudden infant death syndrome exact cause is unknown iii May be due to congenital DRG problem or cardiac arrhythmia iv Baby sleeping on back decreases SIDS v If one child has this problem then it s siblings will also have this problem vi Mother smoking in pregnancy increases SIDS vii Child abuse may have skewed SIDS statistics Pneumothorax a Collapsed lung b Rupturing thorax air enters intrapleural space c Pressure equalizes lung collapses on ruptured side 5 00 V d Decreased flow on good side e Danger of kinking of great veins if opening remains f Reclosed normal breathing on good side lung reinflates Asthma a Episodic or chronic wheezing tightness of chest b Increased morbidity and mortality c Airway Obstruction i Increased mucus production in response blocks airway ii Reduces flow d In ammation i Response to allergies increase IgE Walls get thicker Increase mast cell release of histamine and other cytokines Edema decreases air flow i iii iv v e Bronchoconstriction i Some cytokines are bronchconstrictors ii Also some cool air and exercise iii Constriction decrease air flow iv SRS A 1 Slow reactive substance of anaphylaxis leokotrienes 2 Powerful bronchoconstrictor during allergic attacks 3 Potentially fatal attack Epinephrine 1 Beta 2 receptors bind Epi relax bronchioles increase air flow 2 Rescue from serious allergic attacks 3 Steroids decrease inflammation 9 side effects significant 4 High levels of epinephrine can kill you Emphysema a Cigarette smoke and coal tar are most common causes b Decreased alphaantitrypsin i Lungs have digested enzymes for defense ii Alphaantitrypsin protects lung tissue from digestion 1 Healthy lungs produce this it blocks the trypsin that works against the bacteria in the body so that the lungs don t consume themselves Inhibit alphaantitrypsin production and enzyme digest alveoli iv Decreased number of alveoli and increased size of remaining alveoli c Surface area i Progressive decrease in surface area ii May need pure 02 to fill Hb iii Irreversible right heart enlarges and fails iv You usually only use 10 of your lungs but at the beginning stages of emphysema you use more and more Cystic brosis Recessive gene Most common fatal genetic disease in Caucasians Decreased Cl channel activity Loss of airway Na and water mucus sticky and digestive enzymes increase Increased infection lung destruction fatal Max age used to be 25 now it s 40 Use steroids to treat lt V w m agggz i Exercise help you live longer PSL 250 Lecture 32 The Kidney Renal Filtration and Reabsorption 1 N V U V b V Renal Functions 3 Filters waste from blood b Maintains blood volume controls blood pressure c Maintains blood osmolality how concentrated the blood is d Uses filtration gets rid of everything reabsorption taking back the good stuff secretion Nephron a Functional unit of the kidney b Has vascular system and tubular system c All by cells and proteins in blood can be filtered d Most reabsorbed remainder urine e Vascular system i 2 capillary systems 1 for filtering and 1 for reabsorption ii Afferent arteriole 9 glomerulus filtration 9 80 of blood goes into efferent arteriole 9 peritubalar capillaries reabsorption 9 venules f Tubular System i S shaped ii Bowman s capsule receives filtrate 9 proximal tubule 9 loop of Henle 9 distal tubule 9 collecting duct 9 ureter 1 Ureter carries urine from kidneys to the bladder concentration cannot be changed that this point iii Variable reabsorption hormonal control of volume and osmolarity 1 Absorb all glucose if healthy most water Glomerular ltration a From glomerulus into Bowmann s capsule i Glomerular capillaries have very wide pores that allow fluid to be transferred easily between the glomerulus and Bowmann s capsule Only cells and proteins not filtered Inulin i NOT insulin ii Fructose polymer iii Small enough to be filtered not reabsorbed or secreted iv Inject in blood measure in urine proportional to amount of filtrate 1 Used to measure glomerular rate GFR 2 GFR in young healthy adults quot 125 mlmin or 140 of total blood volume a 8 minutes to filter for 1L of blood 40 minutes to filter all 5L of blood HydrostaticOsmotic Pressures i Hydrostatic pressure BP force into bowman s capsule ii Osmotic pressures so much fluid is filtered remaining proteins have higher than normal OP iii Net lots of filtration Control of the GFR i Afferent arteriole radius controls entry to glomerules ii Afferent arteriole dilation increases GFR iii Afferent arteriole constriction decreases GFR 1 Sympathetic nervous constrict afferent arteriole decreases filtration and decreases blood volume lost in urine decrease GFR Tubular Reabsorption Must recover must filtrate 125 filtered 124 mlmin reabsorbed 1 mlmin urine 9 14 Lday 125 filtered 123 mlmin reabsorbed 2 mlmin urine 9 28 Lday Excess urine loss in diabetes 9 decreases blood pressure 9 shock pathologically low blood pressure 9 death Transport maximum 35 D V m V nave m V i Transport maximum is limit of transport due to limited number of carriers ii Different carriers for different molecules iii Glocosuria 1 When glucose stays in urine it draws water to it osmotically this is what happens with diabetes too much sugar in blood stream 2 3x s more than normal carrier capacity filtered load 3 If glocusuria in urine blood must have at least 3x s more glocosuria than normal Sodium Reabsorption i Controls reabsorption of many other molecules ii Na pump only on basolateral side of tubular cells ATP needed for energy Tight junctions prevent flow in spaces between cells Caffeine decrease Na reabsorption and increases urination Sodium reabsorption drives the reabsorption of everything else 1 In blood 151 water 2nd sodium Cotransport i Carries Na and cotransported molecule i39 Glucose amino acids bicarbonate Cl are cotransported with Na during reabsorption iii Energy use is Na movement down gradient into cells iv H20 follows osmotically at proximal tube v Variable H20 reabsorption at distal tubule and collecting duct Glucose Reabsorption i Binds to carrier with Na on luminal side to enter tubular cell ii Separate nonNa glucose carrier moves glucose into interstitial space 1 Same mechanism used in digestive tract 5 Proximal Tubule Water Reabsorption a 6070 of water reabsorbed into proximal tubule b 180 Lday filtered quot 1 L of urine variable c 500ml of urine minimum per day to remove toxins d Osmotic reabsorption of water follows solutes especially Na e 90 of all college students are dehydrated ES 5 3533 339 V Lecture 33 Renal Control Secretion amp Filtrate Dilution 1 ReninAngiotensin System a Maintain BP by increasing Na and H20 reabsorption b Decrease renal BP 9 release of rennin from the kidney JG cells c Renin is a protease in your blood stream i ase enzyme d Production ofAngiotensin 2 i Renin converts angiotensinogen into angiotensin 1 ii Angiotensin converting enzymes ACE converts A1 9 A2 iii ACE is the walls of the lung capillaries e Effect ofAng 2 i Powerful vasoconstrictor 9 increase blood pressure 1 Constricts blood vessels all over the body 2 Short term affect ii Causes release of aldosterone from adrenal cortex 1 Increase in blood volume 2 Long term affect f ACE Inhibitors i Block production of Ang 2 ii Used as treatment for modest hypertensionmildly elevated blood pressure iii Few side effects 2 U V b V 1 BUT it may produce fetal development problems Tubular Secretion a Extra removal from plasma b Carriers and pumps move material from tubular cells into filtrate c Most secretions is at proximal tubule d Organic acids and bases secreted poisons medicines dyes food additives i Present in urine ii Orange urine from eating too many carrots e Renal Blood Flow PAH i PAH is injected in veins and you measure its appearance in your urine ii PAH is total secreted from plasma iii Appearance in urine proportional to renal blood flow through kidneys iv RBF 2025 of cardiac output f H Secretion i Carbonic anhydrase in tubular cells makes H and HC03 ii H secreted in both proximal and distal tubules iii Uses Na H counter transport H into filtrate iv HC03 9 interstitial fluid net loss of H g K Secretion i K reabsorbed in exchange for Na in proximal tubule ii The Na pump activity increases tubular cell K which increases its secretion by the proximal tubule cells iii Since K and H both exchange with Na an increase in the secretion of one decreases secretion of the other iv Cardiac problems when K amounts change Plasma Clearance a Plasma clearance How much plasma has something been taken out of i It is the volume of plasma from which as amount of material has been removed b Measure of the kidneys ability to remove a substance from the plasma c If a substance is filtered out not secreted or reabsorbed like inulin then its plasma clearance is the GFR glomeliur filtration rate d If the substance is both filtered and secreted its clearance is greater GFR e If a substance like PAH is filtered and entirely secreted its plasma clearance is the renal blood flow 2025 of f Kidney problems are what prevent us from llliving forever Loop of Henle a Creates osmotic gradient in kidney and medulla b 300 mOsm milliosmoles at cortex 1200 mOsm in deep medulla of your kidneys i This gradient allows you to produce urine 1 Dilute light colored releasing water 2 Concentrated yellow holding on to water Filtrate at the end of the loop of Henle is 100 mOsm Plasma is 300mOsm this is the perfect level Counterconcurrent Multiplication i Descending limb of Loop of Henle is H20 permeable ii Ascending limb of Loop of Henle is H20 impermeable H K Cl pumped out iii Filtrate entering distal tubule always dilute quot 100 mOsm 1 Runners who overhydrate problems in potassium ion rho3 VV Lecture 34 Urine Production amp Bladder Function 1 Collecting Duct a Goes through from cortex to medulla b Always dilute filtrate at cortical end 3 V V V V c Responds to vasopressin no VP 9 little water reabsorbed i Dilute urine d Vasopressin i Hormone released in brain also called ADH ii From posterior pituitary iii Released when plasma osmolarity high iv Causes insertion of aquaporin s in Collecting Duct membrane v How to survive on a desert island mix 13 fresh water with 23 salt water 600mOsm that you can survive on vi Aquaporins 1 H20 channels H20 goes through aquaporins 2 Osmotic pressure of solute in medulla 260 mOsm draw water near 3 Retain e Diabetes Insipidus i Type 1 and Type 2 are involved in sugar metabolism tasting diagnosis 1 Diabetes mellitus lot of sugar in urine 2 Diabetes insipidous does not taste sweet ii Either decrease vasopressin production or lack of kidney response bad receptor iii Excess water loss 9 shock 9 death iv Need to drink excess water to survive Urine Buffering a Filtrate pH must be 45 or greater for H to enter filtrate b Bicarbonate and phosphate from filtration and ammonia from tubular secretion buffer urine c Ammonia is associated with the smell of urine Aldosterone Effect a Increase number of inactive Na carriers on luminal side of collecting duct tubular cells i This increases Na reabsorption in collecting duct b H20 follows osmotically c K reabsorption is reciprocal to Na d Secondary Hypertension i Reduced renal artery flow decreases renal Blood Pressure 9 excess renin 9 increase Blood Pressure ii Treat with ACE inhibitors to block angiotensin 2 production iii Diagnosis by determining RBF with PAH Renal Dysfunction a Wide glomerular pores 9 protein in urine 9 edema due to low protein b Loss of concentrationdiluting 9 loss of nephrons multiple causes i Protein blockage in the kidneys can cause loss of nephrons c Acidosis by lack ofammonia reduction H excretion 9 decreased neural function Sodium Dysfunction a Excess Na retention leads to edema hypertension b Decrease filtering excessive aldosterone leads to heart failure Bladder Function a Storage of urine b No changes after leaving kidney c Ureter Entry i Ureter connects kidney to bladder Ureter passes inside bladder wall at an angle Increase bladder pressures closes ureters prevents backflow Kidney stones are calcium clumps iv 1 Don t drink enough water d Bladder Sphincters i Spinal reflex relaxation of internal sphincter when bladder pressure increases ii Relaxation of external sphincter follows 1 Under skeletal control iii Cortex can overcome relaxation of external sphincter iv Parasympathetic neurons increase blood e Control of Micturition i The ECF is the pool of available material for cells ii lnput comes from ingestion or metabolic production iii Output occurs from excretion or consumption iv Balance must occur in the long run with input output v Pelvic floor muscles can be stretched during childbirth 1 Can return to full functional affect after delivery if they are exercised Lecture 35 Fluid Balance 1 N V Balance Concept a The ECF is the pool of available material of cells b lnput comes from ingestion of metabolic production c Must occur the long run within input output i Homeostasis d Negative Balance i Output is greater than input ii Net reduction in pool concentration e Positive Balance i lnput is greater than output ii Net increase in poor concentrations Fluid Balance a Balance of H20 in the body b 60 of the body is H20 with adipose tissue 39 Plasma 90 H20 soft tissue 7080 water bone 22 water because of bone marrow adipose 10 water 1 Too much caloric intake after liposuction causes abnormal growths in adipose tissue c Intracellular fluid i 23 of total body is H20 ii K dominated with protein d Extracellular Fluid i 13 of total body water ii Na dominated iii Plasma 1 20 of extracellular fluid with protein 2 28 liters does not include red blood cells white blood cells or platelets e Interstitial Fluid i 80 of extracellular fluid has no protein ii Four time more fluid in interstitial fluid than in plasma f Minor ECF Component i Relatively small volume lymph cerebrospinal fluid CSF saliva etc ii Will change if there is a change in your volume of water iii 3 3 1 Ex Sweating a lot and becoming dehydrated decreases CSF a CSF protects the brain from the skull important for athletes Extracellular Fluid Volume Regulation Regulation of volume needed for long term blood pressure control m b Changes in blood pressure cause shift of fluid between plasma and interstitial fluid c Blood Pressure Control i Short term A drop in pressure causes 1 Autotransfusion movement of fluid from interstitial fluid to plasma maintains BP 2 Drop in blood pressure decreases baroreceptors activity ii Long term 1 Control of volume is balance of thirstintake and kidney fluid excretion d Salt Intake i Kidney needs 5g of NaClday for fluid loss in sweat urine and feces 1 Average intake is 105g NaClday because salt acts as a preservative 2 Excess is secreted in urine 3 People fought wars over pepper because food was oversalted ii Cl follows Na need some water loss to get rid of excess sodium 1 Diuretics decrease the reabsorption of sodium 9 cause fluid loss 9 decreases blood pressure e Salt Excretion i Kidneys good at eliminated Na but increase retention increases blood pressure ii Must balance 105g 1 day input iii Fitness reduces Na content in sweat iv ReninAngiotensinAldosterone System 1 Long term control of Na excretion controls blood pressure 2 Everyone has their own set point for blood pressure ECF Osmolarity Control Needed to prevent swelling or shrinking of cells Total amount of material in volume regardless of consumption production is osmolarity Ions i Na and K dominate the osmolarity of intercellular fluid and intersisitial fluid ii Other nonpenetrating substances like proteins also contribute to its osmolarity 35 iii If you puta cell in pure water water would come into the cell and the cell will swell until the membrane ruptures 1 Never give someone a transfusion of pure water 2 Normal ICF and IF osmolarity is 300 mOsm d Tonicity i The standard for tonicity is not the number of dissolved particles but the behavior of particles in the solution standard is red blood cells ii Cells swell in hypotonic solutions iii ECF is rarely hypotonic Hypertonicity i Cells shrink in hypertonic solutions gt200 mOsm ii Dehydration can occur because of low intake of water excess loss of water diabetes 1 90 of college students are dehydrated because they drink liquids with low water content 2 People who die in marathons die because they are overhydrated iii Vasopressin 1 Controls tonicity 2 Controls osmolarity of urine 3 VP adds aquaporins to collecting duct increase water reabsorption m V v V Water Intake i Fluid drinking food intake metabolism adds H20 ii Balance H20 loss from lungs sweat skin feces and urine 1 If you sweat a lot then you won t have a lot of urine iii Dysentery and chronic diarrhea are a major problem in third world countries water retention problems 5 Osmoreceptors a Receptors in hypothalamus that control vasopressin VP release b Increase osmolarity 9 increase VP release and water retention c Decrease osmolarity 9 decrease VP release and increase water extension Lecture 36 Acidity 1 Acid a Acids are AH acids dissociate into A and H b Strong acids like HCl in the stomach completely dissociate c Weak acids like H2CO3 carbonic acid partially dissociate 2 Bases a Bases B can bind to become BH b The only significant physiological base is ammonia NH3 becomes NH4 c Ammonia buffers renal filtrate allowing more H excretion 3 pH a measures of H in a solution b pH long H increases in H can decrease in pH c the average blood pH is 74 i blood pH below 735 is acidosis blood pH above 745 is alkalosis 1 acidosis is far more common than alkalosis d the average cell pH is about 7 i cells will have bigger pH shifts than blood e venous blood is more acidic than arterial blood because it has more carbon dioxide 4 Acidosis Effects a alkalosis makes neurons hyperexcitable b acidosis depresses the neurons especially in the CNS c acidosis in general decreases enzyme activity but a few increase i digestive enzymes work at a low pH d acidosis causes increase H excretion and therefore decreases K excretion increases K causes cardiac and neural problems 5 Sources of H a Small amounts of food such as citric acid i You would have to drink a liter of lemon juice to double the acid in your stomach b Most generated in the body carbonic acid from C02 sulfur and phosphoric acids from proteins metabolic acids such as lactic acid 6 Control of H a H is controlled in three ways i Chemical buffering ii Respiratory control of C02 iii Renal control of H excretion b Buffers i Different buffers work in different places ii Buffers work by binding H converting A into AH 1 Not everything can act as a buffer even if it has the right charge iii This removes H from the solution and from pH l V iv First line of defense against an increased concentration of H v Extracellular buffering 1 Bicarbonate is the most important extracellular fluid buffer 2 HC02 binds H to form H2C03 which dissociates to C02 and H20 3 Hemoglobin protein in red blood cells buffers H produced by C02 increases in venous blood vi Intracellular Buffering 1 Proteins in cells bind H in ICF 2 In some cells especially muscle cells phosphate heps buffer ICF vii Urine Buffering 1 Phosphate and bicarbonate are dissociated acids that buffer rena filtrate 2 Ammonia is a base that also buffers rena fitrate c Respiratory Control of H i Second line of H defense works with nonrespiratory sources of H ii Increased H or increased C02 9 increases depth and frequency of respiration iii This reduces C02 in blood reducing H back toward norma d Kidney Control of H i Third line of H defense ii Removes H from any nonrenal source in the body iii H excretion 1 H ion pumps in the renal tubules secrete H into the filtrate 2 Urine pH is normally 60 but can be as low as 45 30x s more H ions serious problem AcidBase Imbalances a Pathological changes in the control of H result in pH changes b These can be compensated by respiratory lungs and renal kidney systems if not of respiratory or renal origin c A system cannot compensate for its own problem i rena problems require respiratory compensation respiratory problems require rena compensation d Respiratory Acidosis i Normal C02 retention from hypoventilation ii Lung disease drugs nervemuscle disorders breath hoding iii Renal compensation by increase H secretion 1 Overdose of opiatesdrugs e Respiratory alkalosis i Decreased CO2 by hyperventilation 1 Caused by fearanxiety aspirin poisoning conscious breathing at a high or low rate ii Decreased H secretion or removal of condition f Metabolic Acidosis i Most common acidbase disorder ii Severe diarrhea loss of bicarbonate iii Excess H production during fat use is diabetics iv Exercise leading to lactate and H production v Kidney failure cannot excrete H or conserve HC03 g Metabolic Alkalosis i Decreased in H for nonrespiratory reasons ii Vomiting oses H in vomitus iii Excess bicarbonate ingestion iv Decrease respiratory rate and retain H in kidneys to compensate v H retention increases K oss Lecture 37 Cardiovascular Regulation amp Hypertension 1 Local Control N V a Local means nonneural factors not neutrally controlled b Decrease P 9 Decrease flow 9 homeostatic tissue response 9 increase flow c Auto regulation each organ controls local blood flow i fan organ has a decrease in blood then it will produce dilators to draw more blood to it ii Active hyperemia d Metabolic Vasodilators i Active tissues produce vasodilators ii ATP use 9 increase adenosine production iii Adenosine is a strong vasodilation active hypertension e Endothelial Factors i Paracrines ii Released from endothelium affect vascular smooth muscle VSM iii Nitric Oxide 1 Hormonalneural activation 2 Increase NO 9 relaxes vascular smooth muscle 9 increase blood flow iv Endothelin 1 Peptide 9 constricts vascular smooth muscle 2 Decrease flow 9 increase blood pressure 3 Stimulates of endothelin increase gene activity that make SE Baroreceptors a Stretch receptors in carotid sinus and aortic arch needed because blood vessels expand and contract b Detect changes in BP after baroreceptor activity c Input to medulla i Baroreceptors send neurons to medulla in brainstem d Control of vasoconstrictiondilation i Cardiovascular control center CCC in medulla ii CCC controls sympathetic and parasympathetic output iii Homoeostatic short term control of BP iv Sympathetic decrease BP 9 decrease baroreceptor input 9 increase sympathetic output 9 increase in BP heart rate and vascular smooth muscle 1 Postural hypertension feeling dizzy after standing up too fast takes five heartbeats to normalize v Parasympathetic increase BP 9increase baroreceptor input 9 increase parasympathetic output 9 increase BP lower HR e Resetting i Body adjusts to its own quotnormalquot blood pressure ii Adaption to prolonged BP change occurs over days 1 Ex Taking medication for high blood pressure medication lowers BP and body rebounds Hypertension 5152 D V Chronic elevated BP and every group is affected by it Multiple causes dozens of things could cause it several small changes cause increase in BP Cardiac Effects i Hypertrophy against increased load diastolic pressure ii Increased oxygen use heart attack when coronaries constrict iii With age increases in systolic pressure increase stroke age Essential Hypertension i Causes unknown but we treat the symptoms which is still effective 1 Reduces pathology the risk of illness or death ii 10 increase in diastolic pressure needs 30 more energy iii 20 increase in diastolic pressure need 7080 more energy e Renal Hypertension 39 Decrease blood flow to kidneys cause increase kidney renin release ii Renin converts Angiotensinogen to Angiotensin 1 A1 iii Angiotensin converting enzyme ACE in lung capillaries convers A1 to Angiotensin 2 iv Angiotensin 2 increases BP strong vasoconstrictor and causes aldosterone release from adrenal cortex v Aldosterone increase Na reabsorption and H20 reabsorption by kidneys more volume f In Pregnancy i Placental factor causes vasoconstriction ii Preeclampsia is hypertension during pregnancy iii Can t findmake drugs that work specifically on a placenta g Drug Treatment i Often used in combination ii Varying side effects iii Diuretics 1 Increase Na excretion lowers blood volume decrease BP 2 Increases urine output and number of times you go to the bathroom and decreases total amount of blood in body iv ACE Inhibitors 1 Blocks the conservation of Angiotensin 1 9 2 a All ACE does is this conversion so it s easy to block it v aAdrenergic Receptor Blockers 1 alpha blockers 2 Stops sympathetic constriction of VSM block NE effects 3 Fewer Ca channels open less Ca entry less force 4 A lot of cells have alpha adrenergic receptors causing significant side effects vi BAdrenergic Receptor Blockers 1 beta blockers 2 Blocks NEEPi effects on the heart less Ca entry 3 Decreases force of cardiac contractions vii Calcium Channel Blockers 1 Decreases VSM contraction clocks tone 2 Almost impossible to control BP when this is used 3 Every cell uses calcium channels side effects are wideranging and significant can t predict the side effects 4 Last resort 4 Shock 3 Very low BP b Loss of blood toxic vasodilation c Reversible shock can recover from i Epinephrine increases BP side effects significant d Irreversible shock multiple organ failure due to low BP e Death results only different between the two Lecture 38 Digestion and Absorption 1 Carbohydrate Digestion 3 Must be reduced to monosaccharides to be reabsorbed b Complex Carbohydrates i Chains of sugars usually glucose ii Different complex carbs have different links between sugars iii Starch is different than cellulose we can t digest V V iv Sugar in fruit is often monosaccharide and sometimes fructose or glucose Enzymes i Produced in the mouth and pancreas ii Amylase converts starch to disaccharides start to taste sweet iii Disaccharides are in wall of the small intestine iv Disaccharides convert disaccharides to monosaccharides 1 Sucrose is converted to glucose v Lactose Intolerance 1 Lactose is milk sugar disaccharide of glucose and galactose 2 If no lactose is produced no digestion of lactose 3 Bacteria in large intestine use lactose as food source a Gas and diarrhea produced d Absorption i Have 30ft of small intestines ii Complete all sugars totally absorbed 1 Otherwise this causes diarrhea iii No diffusion use glucose transporters Sodium Dependence i Glucose cotransported with Na into epithelial cells ii Transport of glucose from epithelial cells to interstitial fluid uses a nonNa glucose transporter Protein Digestion a Some in stomach but most in small intestine b Proenzymes i Released in protected form ii Acid then pepsin converts pepsinogen into pepsin iii Enterokinase stomach enzyme in SI wall converts trysinogen into trysin iv Trysin then converts other pancreatic proteases into active form c Peptidases i Both from pancreas and on small intestine wall ii Convert peptides into amino acids iii Some di and tripeptides absorbed d Absorption of Protein i Use amino acid transporters in mucosal wall ii Some use Na Cl or no cotransporter iii Sources of Protein 1 50 food 25 digested enzymes 25 mucosal cells 2 No dietary protein in feces e Infant Protein Absorption i Newborn can absorb protein directly until tightjunctions form ii High amount of GG in colostrum provides protection by fitting between the cells 1 Mothers immunity is passed into the child for the first two weeks Lipid Fat Digestion a Mouth stomach and small intestine has lipases b Pancreatic lipases enter duodenum in active form c Lipases i Lipases convert triglycerides into monoglycerides and free fatty acids ii Convert lipids to absorbable form d Micelles i Bile salts from liver emulsify MG FFA and cholesterol 391 V m V ii Fats diffuse into mucosa at brush border Absorption I ii TG and cholesterol for chylomicrons iii Chylomicrons enter lymph through thoracic duct to blood iv Portal Vein 1 Carries water soluble foods directly to liver 2 Liver processes and detoxifies foods 3 Fats 9 lymph 9 blood 9 everywhere 9 liver 4 Electrolyte Absorption Salt all H20 soluble 9 portal vein S has tight junctions Salts use carriers channels and pumps to go through cells Water i 2000 mlday ingestion ii 7000 mlday secretions iii 200 mlday in stool iv Follows other absorption osmotically Sodium i Most Na enters through cells energy gradient from Na pumps on basolateral side of mucosa as in kidney ii Some Na entry through leaky tight junctions Potassium i K enters down concentration gradient through channels ii K exchanged from Na last electrolyte absorbed iii During diarrhea K lost too fast for reabsorption iv Active transport of K in COLON Bicarbonate i Huge secretion by pancreas buffers acids in duodenum ii Reabsorbed by concentration gradient in SI 5 Vitamins a Watersoluble B amp C vitamins rapidly absorbed rapid loss of urine b Must take B amp C daily c 312 absorption needs intrinsic factor from stomach d Vitamins A D E and K are fat soluble 9 micelles 9 lymph 6 Minerals a Ca 3080 absorbed Vitamin D dependent b Ca binding proteins and Ca ATPase increase Ca entry m V MG and FFA cross and reforms into T6 in mucosal cells In 935 V V m V v V Uh V Lecture 39 GI Intro Mouth amp Esophagus 1 GI Layers a Mucosa epithelial cells first layer of cells around the lumen where the transfer of materials occurs b Submucosa longitudinal muscle runs lengthwise down the tube submucosal plexus c Muscularis circular and longitudinal smooth muscle myenteric plexus d Serosa outer epithelial layer produces serosal fluid i Stomach gurgling sound is coming from small intestines circular muscles is squeezing down on air pockets 2 GI Innervation a Plexuses neurons control local contractions b Longitudinal muscles propulsion of chime c Circular muscles mixing food and secretions d Parasympathetic Neurons m V v V i Parasympathetic nerves control digestion and dominate the autonomic nervous system ii Activate plexus 9 increase GI activity iii Sympathetic neurons decrease DI activity Basic Electrical Rhythm i Variable electrical baseline Ca2 and K channels open close ii Contraction when BER reaches threshold and APs occur Migrating Motility Complex i Storage contraction migrates from stomach to end of the small intestine SI ii Starts as previous meal nears complete digestion iii Clears stomach and SI in anticipation of next meal GI Hormones 1 Released in different areas b Both upstream and downstream effects c All hormones are released into your blood stream d Gastrin i From stomach protein is the strongest stimulus for release of gastrin ii Increase stomach secretion ofacid and pepsinogen iii Increase SI ilocecal valve relaxation 9 empties SI iv Initiates mass movement in LI that triggers defecation e CholecystokininCCK i Secreted by duodenum into blood when fat or protein present ii Three effects 1 Cause contraction of gall bladder 2 Cause release of pancreatic digestive enzymes 3 Inhibits stomach secretions f Secretin i Secreted from duodenum into blood when H in duodenum ii Increase secretion of pancreatic bicarbonate into pancreatic duct iii Bicarbonate neutralizes stomach acid in duodenum Mouth a Little digestion here b Almost no absorption only some in medicine c Nitroglycerine absorbed by oral mucosa i Very hydrophobic so fat soluble that it can diffuse through the membranes under your tongue and can get to your heart through your veins in seconds I Secretions i Bicarbonate neutralizes acids ii H20 amylase lipase mucus to coat food iii Lysozyme antibacterial enzyme e Swallowing deglution i Two muscular systems one voluntary and one involuntary ii Boluses formed food mixed with saliva iii Voluntary propulsion to pharynx iv Reflex relaxation of upper esophageal sphincters Esophagus a Tube to stomach sphincter at each end b 59 seconds transit time to stomach c No digestion or absorption d Sphincters i Upper esophagus sphincter relaxes upon swallowing ii Peristaltic contractions behind bolus force it into stomach iii Lower esophagus sphincter LES normally tightly closed relaxes to let bolus in e Re ux i Acid into esophagus through LES ii Acid irritates the esophagus can result in ulcers pain and damage referred to as heart burn iii Loss of neural input most common cause f Gas i In stomach ii Swallowing gas some burped out some absorbed some to colon iii Most colonic gas is bacterial Lecture 40 Stomach Pancreas amp Liver 1 Stomach a Holds contents kills pathogens starts protein digestion b Relaxes as food enters holds up to 1 liter c Most digestion occurs in the small intestine d Three parts fundus antrum body e Structure i Coated with mucus ii Lining has gastric pits cells produce secretions iii Mucus coats gastric pits prevents HCI killing cells f Secretions i Pepsinogen ii HCL separate H and Cl pumps pH 12 iii Mucus gastrin intrinsic factor for 312 absorption g Motility i Peristaltic wave 3min fundus to body to antrum ii Forces food into antrum crushes boluses there forms chyme that is squirted into the small intestine through stomach contractions 1 Chyme is a mixture of food and secretions 2 Stomach acids kill off anything in the stomach h Emptying i Pyloric sphincter separates antrum and duodenum ii Pyloric sphincter squeezes shut as boluses are crushed iii Only a small amount of chime squirts through i Ulcer i Open sores in stomach because cells exposed to acid 1 When there is a break in the mucus coat cells are killed off ii Histamine is released 1 Stimulates the secretion of acid by your stomach 2 Acid 9 damage 9 histamine 9 more acids 3 Positive feedback loop 4 Treatment stop acid secretions neutralizes acids iii H Pylori Bacteria 1 Live in gastric pits 2 gt50 of all ulcers 3 Hard to get to due to mucus antibiotics can kill H Pylori 2 Exocrine Pancreas a Secretes bicarbonate solution to neutralize stomach acid b Secretes enzymes for digestion c Duct system i Carries solution to duodenum ii Duct cells secrete bicarbonate solution d Alkaline Secretion i Bicarbonate or alkaline solution also called Pancreatic Aqueous Alkaline Solution PAAS 1 Made up almost entirely Na Bicarbonate quot 45x s more bicarbonate than plasma 2 Neutralizes acids ii 15 Lday or more iii Regulation 1 Increased H lower pH in duodenum 9 secretion of secretin release into blood 2 Secretion from duodenum causes releases of Na Bicarbonate solution 9 PAAS 3 Carbonated drinks lower pH good to drink when you don t trust the water in the area e Enzymatic Secretions i Duct cells produce enzymes lipase amylase proteases Proteases released in protected form iii Lipase and amylase released inactive form iv Pancreas has trypsin inhibitor for protection v Regulation 1 Fat or protein in the duodenum causes CCK release 2 CCK causes acinar cells to release 3 Enzymes carried to duodenum by DAA s 4 Parasympathetic neurons increase enzymes release sighsmell response 3 Liver a Pancreas and liver and quotaccessory organs that don t do any digestion b Releases bile into duodenum to emulsify fats c Mostly undifferentiated cells 1000 s of metabolic reactions d Makes plasma proteins e Blood Supply i 2 sources merge at liver sinusoids ii Hepatic artery supplies oxygenated blood from heart iii Portal vein carries water soluble foods from small intestine f Bile Sa1s i Major component for bile made by hepatocytes ii Released into bile canaliculi on opposite side from blood iii Bile salts for micelles 1 9095 of bile salts reabsorbed at ileumrecycled g Bilirubin Metabolism i Turn over 8 of red blood cells every day 1 RBC look red because it matches the frequency of red wavelengths ii Bilirubin formed from heme of lysed RBC s fat soluble sticks to albumin circulate bound to albumin iii Released to liver cells 9 modified to H20 soluble form 9 most to bile 9 feces iv Some is absorbed at the ileum and excreted in urine v Bilirubin yellow wavelength 1 Provides color for both urine and feces vi Jaundice is a buildup of bilirubin problem in newborns liver is not processing the bilirubin from fat soluble to water soluble h Gall Bladder Function i Stores bile between meals when Sphincter of Oddi S of 0 closed ii CCK relaxes Sphincter of 0ddi and contracts the GB 9 bile enters duodenum iii Gallstones 1 Calcium bilirubinate some or cholesterol stones most 2 Form in gall bladder w glycoprotein binding can be as big as a centimeter across 3 Can block Sphincter of 0ddi gall bladder binding 4 If gall bladder removed bile duct expands to hold bile Lecture 41 Small Intestine and Large Intestine 1 Small Intestine a Primary site of digestion and absorption b Structure i Duodenumjejunumilium ii Many folds increase surface area 600 folds iii Small intestine deals with 9 Lday 2 food 7 secretions 1 12 Lday to color 200 mL in feces iv Villi 1 Folds of SI wall tissue 2 Crypts of Lieberkuhn base have the highest rate of mitosis a Cells migrate upward die by digestion b Cells replaced every 3 days v Microvilli Brush Border 1 Fold of cell membrane at the tips of villi cells 2 Site of absorption 3 Bound enzymes on surface enterkinase disaccharides peptidases etc a Have lots of enzymes that are exposed to food that needs to be digested c Mucus i Secreted w H20 ii Contains glycoproteins iii Covers S epithelium in C of L and upwards iv Protection from digestive enzymes d Motility i Basic Electrical Rhythm BER higher at duodenum than at ileum ii Moves chyme down S peristaltic wave of longitudinal smooth muscle iii Segmentation mixing contraction of circular smooth muscle e Malabsorption i Decrease Amino Acids absorbency 9 wasting decrease muscle mass a Wasting loss of skeletal muscle mass occurs during starvation or malabsorbance ii Decrease carbs and fat absorbency 9 increase stool and gas and decrease vitamin absorbency iii Autoimmune Crohn s and allergic gluten anteropathy disease 1 No one has ever been cured ofan autoimmune disease iv Diarrhea 1 Multiple cause most common S motility gt absorption 2 Loss of H20 and K potentially serious or fatal neuralheart problems 3 Dehydration leads to shock 4 Travel change in waterelectrolytes kill bacteria of E Coliother bacteria in food 2 Large Intestine Colon a Handles absorption of H20 and Na as well as some K b No nutrient absorption because by the time the chyme reaches the Ll everything will have already been absorbed in the SI i Bacteria that lived in the U can produce amino acids needed in diet c Structure i SI 9 cecum 9 descending transverse descending colons 9 rectum 9 anus D V Uh V 1 Gastrin released from stomach causes contractions of the Li that moves the material down to the colon and to the rectum ii Internal and external sphincter control anus iii Appendix closed pouch of lymphoid tissue off cecum can live without 1 Appendicitis caused by bacteria eating through the wall of the appendix because it can t get out Gastrioileal Re ex i Food in stomach case relaxation of cecum and allows ileum to empty ii Gastrin relaxes ileocecal valve Absorption i Active transport of Na water follows 1 15 Lday absorbed in large intestines 2 Diarrhea is caused when water isn t absorbed ii FecesFiber 1 Feces is minerals fiber bacteria H20 2 Bacteria grow even during starvation 3 Fiber is cellulose also called ruffage and related compounds 4 Fiber increases colonic activity decreases colon cancer by over 90 a At age 50 get colonoscopy b Colon cancer death rate is 40 Bacteria i E Coli and the other types appear in large intestine soon after birth 1 Acquisition of the bacteria comes from the mother s nipple ii Bacteria require nutrients from the colon mucosa iii May produce useful vitamins and essential amino acids iv Bacteria can t get through adult walls of the large intestine because of tight junctions 1 CAN invade body after radiation poisoning Defecation i Gastrin triggers colonic contractions 9 mass movement into rectum increase pressure ii Increase rectal pressure causes reflex relaxation of internal anal sphincter smooth reflex iii Voluntary control of external anal sphincter skeletal muscle iv Constipation 1 Defecation caries from 3day to 13 days 2 No significant health consequences except discomfort 3 No quotpoisonquot absorption v Flatus 1 Most is bacterial some from ingestion 2 Smell due to sulfides 3 Sound force through external sphincter m V v V 4 Basal Flatal Rate 12 mLhr 1 passagehour 5 Postprondial after eating Flatal Rate 176 mLhour after one helping of baked beans increased frequency a Beans have a substance that inhibit an enzyme Lecture 42 Energy Balance 1 V Energy Input a Energy in ingested foods b Digested food energy trapped in ATP phosphate bonds c ATP used to drive all physiological functions Energy Output a External work used to move objects or the body b Internal work posture shivering internal activities needed for life ion pumping heart pumping synthesis etc c All activities ultimately become heat Basal Metabolic Rate h V on V 8 a BMR energytime x caloriesday b 2000 Caloriesday are 2000 kilocalories day i Walking one mile burns 100 calories ii Eating one large cookie add 100 calories c Neutral Balance i Energy input energy output ii Food energy external work internal work heat d Positive Balance i Energy input gt everyday output ii Energy stored in adipose tissue 9 weight gain e Negative Balance i Energy input lt energy output ii Weight loss first from adipose tissue then from muscle Hypothalamic Control of Intake a Hypothalamus integrates multiple signals matching feeding to energy needs b Balance of hunger and safety c Neuropeptide Y i Released by HT stimulates appetite d Melanocortins i Released by HT suppress appetite ii NPY and MCs alter brain activities that control food intake Leptins a Secreted by adipose tissue proportional to T6 storage in adipose b Increasing fat stores signals satiety Digestive System Appetite Control a Hormones from the GI tract control hypothalamic release b GhrelinPYY336 i Ghrelin rises before eating and stimulates appetite smelling food while it s cooking ii Falls after eating increase PW release iii PW released during meals and signals satiety quotsense of fullnesssatisfactionquot i The release of CCK signals satiety before digestion has occurred stop eating before the new calories available ii Stimulating CCK with fat or protein early in eating may control food intake amount Social Control Social context family meals habits stress loneliness distraction etc i Caloric intake often strongly influenced by outside factors Obesity decreased exercise BM R biochemistry differences habit hormonal differences etc i Increased morbidity and mortality c Anorexia nervosa physiological starvation K imbalance i Can be caused by pressure from parents Temperature Regulation 986F 37C 1 E m b Convulsions at 106F c Death at 110F death from protein denaturation d Core temperature is regulated shell is variable e Heat Balance i Balance of input and output ii Internal heat must be removed iii Multiple heat exchange mechanisms f Heat Exchange i Radiation by electromagnetic waves sun fireplace ii Conduction transfer by contact from warm to cold iii Convection airwater currents increase transfer iv Evaporation of water from skin removes heat 1 Sweat increases evaporation dripping doesn t 2 Fitness decreases sweat salt content increased evaporation g Heat Production i Muscle contraction 1 Shivering is contraction without work all heat ii BMR sets lower limit of heat production h Response to Cold I llquotuo39i iwz l Sl X Ur thermoreceptors control responses 1 Decreased skin blood flow goose bumps ineffective 2 Human adaption movement clothing outside sources i Response to Heat i Increased skin blood flow increased sweating adaption Fever RBCs release endogenous pyrogen 9 causes reset of temperature set point in hypothalamus Aspirin blocks prostaglandin production 1 Doesn t make the source of the infection go away but block the set point change to lower a fever doesn t stop the production of endogenous pyrogen Feeling the chills fever is coming on Feeling hot the fever has broken and you re going back to normal 53 Lecture 43 Principles of Endocrinology Circadian Rhythms amp Calcium Control 1 Hormones a Released from endocrine glands into the blood go everywhere b Bind to receptors i Effect in different cells receptor dependent c Hydrophilic hormones bind to membrane receptors d Hydrophobic hormones bind to nuclear receptors alter protein synthesis i Testosterone Plasma Hormone Concentrations a Controlled by feedback mechanisms i Hydrophilic hormones can change concentration rapidly minutes ii Hydrophobic hormones often paritian into adipose tissue 1 This buffers changes in plasma concentration hours b Negative Feedback i Concentrations vary minimally around a set point 1 Falling concentration stimulate release mechanisms 2 Rising concentration inhibit release mechanisms c Neuroendocrine Re exes i Neural activation can produce a rapid increase in hormone release ii Cortisol can change quickly if you re very stressed about something can activate pain receptors 1 Controls repair processes in body 2 Rises when you sleep and falls during the day so it repairs your body at night causing less soreness d DiurnalCircadian Secretion i Daynightaround a day rhythms on a 24hour cycle 1 Entrained by sleepwake or light 2 Actual human cycle is closer to 39 hours but we are used to 24 ii Night shift work put same pair of hormones out of cycle increases junk illnesses Endocrine Disorders a Hyposecretion or hypersecretion i Often related to endocrine or feedback cell receptor malfunction ii Target cell malfunction no response from normal hormonal level 4 Cell Responsiveness a Controlled by the number of hormone receptors available on target cell b Down Regulation i Type of adaptation at the receptor level 1 Spicy food ii Desensitized due to chronic elevated hormone level iii Internalization or chemical modification of receptors iv Ts has down regulation of insulin c Permissiveness i One hormone enhances the response of 2nd hormone ii Thyroid hormone TH increases epinephrine receptor number on target cells TH cranks up receptors for other hormones d Synergism i Two hormones increase each other s activity ii Sperm production iii FSH and testosterone each help the other increase sperm production e Antagonism i One hormone reduces the effects of another hormone ii Progesterone decreases estrogen receptor number of the uterus 5 Pineal Gland a Releases melatonin to help regulate circadian rhythms 6 Biological Clocks a Controlled by the superchiamic nucleus SCN in the hypothalamus i Clock proteins in SCN regulate their own production over a day 1 Clock proteins control the neural outputs of the SCN which in turn controls some hormonal outputs like the cortisol ii External cues keep the SCN on 24 hour rhythm 7 Melatonin a Release from pineal gland is controlled by light and melatonin release is high in dark b Controls lightdark hormonal fluctuations c May help sleep decrease aging and free radicals and salvage the immune system i No link to puberty 8 Plasma Calcium a 90 of phosphate store in bone as calcium phosphate b 99 of Ca stored in bone as calcium phosphate as solid form not contributing to the liquid c Ca 25mm in plasmablood stream d 10quot7 M on cells 9 Parathyroid Hormones m Regulated by Parathyroid hormone PTH PTH increases reabsorption of Ca from bone fluid in spaces and then from calcium phosphate Necessary for life no PTH hypocalcemia Hypocalcemia i Low blood calcium ii Hyperactive nerve and muscle increase Na energy iii Larynx and diaphragm spasms no air 10 Vitamin D a Most comes from the foods we eat a little from exposure to the sun 935 V V b 0 Control of Ca absorption Enhances PTH activity 11 Osteoporosis 3 b C d e 1 20 h century problem quotpink collared jobsquot no longer involve labor not putting load on the bones Decreases estrogen linked to osteoporosis PTH Vitamin D Ca all normal Decreases bone density Less effect if bones are thicker when menopause starts Weight bearing work and exercise thickens bones Lecture 44 Hypothalamus Pituitary and Growth 1 HypothalamusPituitary Structure 3 b 0 Hypothalamus at the base of the brain stalk connects hypothalamus to pituitary i By capillaries that drain the hypothalamus ii And by capillaries at the pituitary Posterior pituitary master gland connected by neural axons i Two hormones Anterior pituitary connected by the Hhypothalamus portal system i Six hormones 2 Posterior Pituitary m b C d m V Hormones synthesized in the hypothalamus Axons and nerve endings in posterior pituitary Two hormones vasopressin and oxytocin Vasopressin i Secreted when osmolarity increases ii Increase H20 reabsorption at the collecting duct iii Stimulates aquaporin insertion in collecting duct membrane Oxytocin i Produced within hours of childbirth Contracts uterus during childbirth ii Causes milk ejection from mammary glands during lactation 3 HypothalamicReleasinglnhibiting Hormones avg d m V Anterior pituitary hormone release controlled by hypothalamus Releaseinhibiting hormone travel by portal system to anterior pituitary Release hormone RH and inhibiting hormone IH control release of 6 anterior pituitary hormones Portal System i Connects capillary beds from the hypothalamus to anterior pituitary 1 Small distance and no dilution means RH and H released in very small amounts but with BIG effects Hormones 1 TSH stimulates the thyroid 2 ACTH causes the release of other hormone 3 Growth hormone growth for first 20 years of life 4 Prolactin no function in males causes secretion of milk 5 LH and SFH effect varies in women also present in males Anterior front Pituitary Hormone Release i Input to the hypothalamus controls RH and H release and input is both neural and hormonal ii Balance of RH and H for particular anterior pituitary hormone controls anterior pituitary hormone release iii Delay in onset of menstrual cycle because of desire to reproduce iv Negative Feedback 4 U39I V l V 1 Anterior pituitary hormone release is regulated by negative feedback always to anterior pituitary sometimes to hypothalamus 2 Target hormone release inhibits anterior pituitary tropic hormone release f Growth Control i Multiple factors affect growth all necessary for full growth 1 Genetics provides base and maximum parent s height 2 Nutrition most important nongenetic factor 3 Proteins vitamins and minerals essential for full growth calories needed 4 Growth can catch up during puberty if there was a decrease in childhood due to protein catabolism quot Growth Hormone 1 Protein from anterior pituitary a Activates second messengers at many organ cell membranes i 15 minute circulation time before metabolism by liver 2 NonGrowth Related Effect a Increase liver glucose production decrease fatty acid release from adipose tissue b Conserves glucose for brain during growth 3 GrowthPromoting Action a Hyperplasma more cell division and hypertrophy of cells b Increase protein synthesis Bone Growth a Growth hormone stimulates growth in bone thickness and length b Bone Composition i Outer layers have compact bone calcium phosphate hardenscollagen makes strong and flexible ii nner layers have spongy bone iii Long bones epiphyses at both ends diaphysis in middle c OsteoblastOsteoclasts i Osteoblasts form new bone and secrete calcium phosphate i39 Osteoclasts resorb bone eats away at epiphyseal plate and create spaces in bone for a longer diaphysis If a girl secretes estrogen from ovaries before DHEA from her adrenal gland then she will start puberty earlier but be shorter beau case she will close off the epiphyseal plates 1 DHEA before estrogen longer phase of bone growth d Bone Length Growth i Length growth occurs at epiphyses osteoblasts extend diaphysis 1 Fuse at puberty osteoblasts catch osteoclasts Control ofGrowth Hormone Release a Hypothalamus releases both GNRH and GNIH b Diurnal effect highest an hour before sleep begins c Exercise physical stress and low blood glucose increases growth hormone release i Children grow taller when they are involved in physical activity and don t overeat Growth Hormone De ciency a In children dwarfism occurs with decreased bone growth i Long bones do not grow as long as they would with GH b No effect on adults because GH stops functioning after age 20 and stops being produced after age 40 GH Excess a Before puberty increased proportional growth b After puberty acromegaly disorder tumors in pituitary gland causes the secretion of GR excess growth of face hands and feet i We usually have a small continuous growth of feed hands nose and chin Lecture 45 Thyroid 1 U V Thyroid Hormone Increase metabolic activity in most tissues b Don t need it to live but life is difficult without it c Decrease TH 9 poor mental health and physical function i Decrease cold resistance mental retardation in children m d Increase TH 9 wasting nervousness increase heat production tachvacrdia Bulging eyes e Thyroid Hormone Synthesis i thyroglobulin a protein is made by follicular thyroid class 1 Exocytosis to colloid iodine added to tyrosines 2 Link together typrosies diiototyrosine DIT and either DIT or monoiototyrosine MIT endocytosis digestion to T3 or T4 f TH Secretion i MIT and DIT recycled in follicular cells ii T3 and T4 secreted into blood number is iodines iii Most secretion is T4 g TH Transport i T3 and T4 circulate bound to protein ii T4 4000 bound 1 free free is active iii Most T4 converted to T3 in circulation iv T3 is more active than T4 h TH Buffering i ASTH lost in urine or to cells other TH comes off protein ii T3 binds weaker than T4 T3 lost faster iii Always lose the same amountconcentration TH Effects All increase metabolic activity Maximizes GH effects on protein synthesis and bone Calorogenic i Increased heat production ii TH bind to nuclear receptors alters gene activity iii Increases cell activity increases fatty acid metabolism increase Na pump activity d Sympathomimetic Function i Required for full sympathetic response ii TH stimulated production ofadrenergic receptors e Heart i TH increase in adrenergic receptors ii Increases heart rate and force of contraction Neural Tissue i Needed for proper central nervous system development in children ii TH required for full neural function response to Ca echoleamines RAS reticular activating system for wakesleep function iii Cortex and basal ganglia need TH Regulation of TH Secretion a By thyroid stimulating hormone TSH from anterior pituitary b TSH Regulation i Decreases blood TH release of RHS from anterior pituitary 1 TSH go to thyroid gland increases thyroglobulin secretion endocytosis and T3T4 production c Hypothyroidism 35 v V i Is a thyroid gland disease or decrease in TSH production or autoimmune attack 1 It decreases BM R lethargy decreases mental and physical function d Graves Disease i Hyperthyroidism nervousness weight loss warmth increase BMR exophthalmos bulging eyes ii Cause is antibody thyrostimulin inulin antibody TSI that binds and activates TSH receptors that increase thyroid gland activity and makes more thyroid hormones e Hashimoto s Syndrome i Autoimmune attack on thyroid gland decreases function and hormones and stops you from making thyroid hormone 1 Leads to hypothyroidism 2 Need sympathetic TH not rare ii If you re going to get an autoimmune disease this is the one to get 1 Can take medication for it because you have thyroid gland storage 4 Goiter a Enlarged thyroid gland b Due to excess TSH or TSI c May produce hypo from decrease iodine or hyperthyroidism from increase TSI Lecture 46 Adrenal Gland 1 Adrenal Medulla a Two layers medulla and cortex b Medulla is the inner layer ofadrenal gland c Similar to postganglionic sympathetic neuron d Secretions i Stored in granules ii EpinephrineNE have strong peripheral effects iii Vitamin C stored and released with EPINE e Effect of Catecholamines i Epinephrine increases heart rate decreases total peripheral resistance TPR and increases CO ii 39 39 39 in increases 39 except in heart and skeletal muscle iii Net effect is INCREASE in blood pressure by vasoconstrictors and INCREASE in metabolic rate 1 Strokes associated with taking too many diet pills f Neural Control i Release determined by baroreceptor activity 1 Decrease blood pressure increase EPINE release 2 Increase blood pressure decrease EPINE release 2 Adrenal Cortex a Outer layers of adrenal gland b Endocrine gland c Each layer make secretes a different hormone d Secretions i Released as made not stored ii All are steroid derivatives of cholesterol 1 Mineral corticoids most important is aldosterone released by Ang 2 and increases the reabsorption of Na Glucocorticoids most important is cortisol most prominent when you re asleep because it fixes damage done to you during the day and breaks down needed proteins for amino acids Androgens DHEA only effects females growth and sex drive androstenediane is a precursor for testosterone in males e ATCH adrenocorticotropic hormone Effect and Control i ACTH from anterior pituitary when cortisol is low stress is high on top of diurnal rhythm ii ACTH causes increase release of all adrenal cortex steroids except aldosterone N 3 3 Circulation ofGIucocorticoids 6 V V a Most bound to globulin proteins b Only free form is active c Takes an hour to get into cells and then1530 minutes to see an effect Glucocorticoid Effects a Cortisol is a quotstressquot hormone necessary for survival b Bind to nuclear receptors to increase protein synthesis c Metabolism i Increases protein catabolism breaking down proteins freeing amino acids for damage repairmaking new proteins Increase plasma glucose and plasma fatty acids 1 Glucose and fatty acids provide energy for repairs d Permissive Actions i Assists actions of glucagon and catecholamines causes vasoconstriction and bronchodilation e Stress i Something is only a stress if ACTH increases ii ACTH increase in cortisol release 1 Short term increase in every day availability amino acid availability catecholamines 2 Long term stress is harmful excess protein breakdown wasting of muscle mass pain a Stressful job f AntiInflammatory Effects i Cortisone shots 1 Used for serious CNS injuries so that brain does not swell and press against skull ii Only at high glucocorticoid levels 1 Decrease swelling decreases histamine 2 Blocks immune system apoptosis death of white blood cells iii Must use antibiotics to prevent infection 1 Not for routine use significant and long term side effects Mineralocorticoids a Aldosterone increases Na reabsorption in the kidney i Has more Na transport molecules in the kidneys Adrenal Androgens a Major effects in females i Similar to testosterone b Nominor effect in males c DHEA i Hormone ii Sex drive and starts growth spurt at puberty in females Estrogen female growth spurt No effect in males testosterone is 100x s stronger Androstenedione 1 Does nothing by itself 2 Can only be made into testosterone 3 Used for sports ii 53 Lecture 47 Fuel Metabolism Insulin amp Diabetes 1 V V AnabolismCatabolism a Anabolism building up and storing proteins and carbohydrates b Catabolism breaking down macromolecules c Balance of buildup of large macromolecules with breakdown controlled by activity and everyday balance Essential Nutrients a quotEssentialquot means essential in your DIET cannot produce in body U V In V l 00 V V i Ex Vitamins b Some nutrients and amino acids 8 of 12 cannot be made in the body c All vitamins must be in diet Nutrient Storage a Glycogen storage in muscle and liver b Fat storage in adipose tissue 0 Brain Glucose Supply a Brain only uses glucose for energy liver glycogen maintains plasma glucose between meals Body will consume muscle for amino acids during starvation b Fats cannot be made in glucose cannot supply energy to brain 0 Absorptive State a Postmeal state several hours after eating If no glucose is available body converts proteins to amino acids to glucose b Many nutrients available from early arrived meal c Absorption of carbs then proteins then fats PostAbsorptive State a Between meals fasting b Use stored energy to supply tissue s energy needs Islet Cells a In pancreas secrete hormones into blood i Alpha cells secrete glucagon ii Beta cells secrete insulin 1 Secretion increase plasma glucose increase insulin secretion a Small enough to leave capillaries through pores Insulin Effects a All aimed at future energy use b Carbohydrates i Seconds increase number of transporters by fusion of membrane transporter vesicles 1 Increase glucose energy into cells 2 Brain and working skeletal muscle don t need insulin because they have so many glucose transporters already ii Minutes increase storage of glycogen in liver and muscle c Fats i Slowest things you digest ii Hours insulin increases lipid storage in adipose tissue d Proteins i Seconds increase amino acid transportentry into cells ii Regulation of Insulin Secretion 3 Minutes increase glycogen storing enzymes in liver and protein synthesis Increase in plasma glucose increase in insulin release i 1 hour sugar meal has rapid rise and fall in glucose insulin stays high b Decrease glucose causes decreased insulin release i Hypoglycemia after sugar meal as insulin stays high after sugar transport complete c Starch meal takes longer to ingest glucose glucose and insulin never gets as high no hypoglycemia 10 Glucagon a Opposite effect of insulin i Increase glycogen breakdown liberates glucose from storage ii iii Decrease plasma glucose increase glucagon release Increase lipid release increase glucose production by liver iv Increase plasma glucose decrease glucagon release 11 Diabetes Mellitus a 039 V n V m V v V Glucose in urine i Type 1 10 autoimmune attack on beta cells ii Type 2 90 obesity and age decrease number of insulin receptors Hyperglycemia i Increase plasma glucose 1 Hemoglobinate test long term glucose indicator ii Increase blood osmolarity exceeds Tm for glucose iii Dehydration 1 Increase urine volume 2 Loss of Na and K 3 Decrease blood volume decrease in BP shock death Protein Metabolism i Proteins and fats are turned into amino acids used and for energy and to make glucose in liver ii Negative protein balance and wasting Fat Utilization i Use fats for energy in insulindependent tissue most ii Fat use increases plasma fatty acids and cholesterol 9 increase in atherosclerosis iii Acidosis 1 Fat metabolism increase in ketone bodies 4C ketoacids a Increase ketosis increase in acidosis increase in breaking rate decrease mental activity iv Coma 1 Acidosis dehydration and hyperosmolarity can all induce coma in diabetes and some coma leads to death Type 1 Diabetes Mellitus i Juvenile diabetes ii These are usually the best patients iii Most prominent in teens but can occur at other ages iv Autoimmune attack on beta cells immune attack gradually destroys beta cells over a 23 years 1 Gradual loss of insulin in production hyperglycemia develops Type 2 Diabetes Mellitus i Loss of insulin receptors 1 Continuous elevation of insulin Associated with obesity in people under 40 Symptoms like Type 1 Obesity 1 Prolonged elevated glucose 9 constant insulin production 9 down regulation of insulin receptors 9 decrease glucose energy and hyperglycemia a Reducing caloric intake helps v Age 1 In elderly people decrease receptor number or receptor availability a Not necessarily associated with obesity but increase weight can increase probability b May take some insulin to maximize available receptors iii E V Lecture 48 Cancer 1 Incidence 3 b 0 Most common cause of death 15 Males prostate gt lung gt colon gt bladder Females breasts gt lung gt colon gt uterine U V b V U39I V d Incidence declining 2year since 1992 e Cancer deaths largest number with percent of incidence deaths i Males lung 100percent that dies within 5 years gt prostate 16 gt colon 45 gt pancreas 100 1 Less than 1 chance that someone with lung cancer will be alive in five years ii Females lung 90 gt breast 22 gt colon 45 gt pancreas 100 1 Pancreatic cancer 56 weeks from diagnosis to death Types a Separated by ability to spread b Benign i Localized can produce problems if tumor crushes adjacent tissues or draws blood from adjacent tissues 1 Treat with surgery 2 Many benign tumors are not cancerous c Malignant i Has metastasized through lymph system ii Surgery to remove large tumors as well as chemo andor radiation to kill cells that have spread Diagnosis a Need biopsy for full diagnosis increasing use of MRI i Tumors often produce hormonal or protein markers Treatment a Combination of treatments will vary with different cancers b Surgery i Remove tumor and some surrounding tissue to make sure all of the tumor is removed c Radiation i Kills fastgrowing cells ii Damages DNA and makes oxygen radicals 1 Also bone marrow and GI side effects I Chemotherapy i Gets into the blood stream and goes everywhere ii Kills fast and growing cells iii Has multiple targets DNA and mitotic spindle 1 Also hair loss bone marrow and GI side effects e Biologic Therapy i Shift hosttumor balance toward host ii Alter T cell antibody production and cytokines to attack tumor Genetics a Single cell gene rates tumor b Not inherited from parents c Even predisposition needs additional mutations i Most women who have disposition to breast cancer do not get it I Mutation i DNA 39 e Tumor Viruses i Only a few cancers are linked to viruses DNARNA viruses alter DNA in host cell Only RNA virus cancer is a type of leukemia DNA viruses have several links 1 Cervical cancer 2 Liver cancer 3 Lymphomas during immune deficiency Ir lead to 39 cell r ii iii iv 6 Cell Biology 3 b n V D V m V v V Uncontrolled growth due to cell changes One mutation is not enough i Malignancy usually needs 5 10 P53 mutations i Most common mutated gene in a tumor ii P53 is used to slow down cell divisionmitosis acts as tumor suppressor iii Mutation leads to genetic instability and resistance to apoptosis Environmental Signals i Effect occurs in cancer cells alter mutations ii Cytokines and paracrines alter Gprotein and enzyme linked processes iii Effect signals to genome that regulate mitosis iv Loss of celltocell connections stops controlling inhibition of cell division Transcription Factors i Control gene activation turn onoff alteration in genes andor factors ii Factors affect expression in tumor cells allowing tumor growth Apoptosis Regulation i Programmed cell death often occurs after mutation 1 Caspases are enzymes controlling apoptosis attack DNA enzymes cytoskeleton and cause cells to die off ii Decreased capase activity in tumors iii Target of new cancer treatments 7 Angiogenesis 8 V 3 Tumors draw blood from surrounding healthy tissues starving them Prevention 3 039 V n V m V Prevent multiple mutations necessary to start tumor Smoking Cessation i Stopping is the single most positive health activity 1 400000 premature deathsyear from smoking 2 Smoking linked to lung larynx esophagus bladder pancreatic cancers 3 Also linked to cardiovascular and pulmonary disease 4 90 who quit do so on their own total quitting most successful Diet i Decreased fat intake decreases cancer rate ii Anticarcinogens in vegetables fruits nuts iii Fiber decreases colon cancer Sun Avoidance i UV radiation causes an increase in skin cancer ii Acute sunburns even in childhood increase risk of melanoma iii Lighter skinned people have greater risk iv Worst skin cancer is melanoma Chemoprevention i New field drugs designed to decrease mutation risk ii Antimultagenic antioxidant antiprolifesative preventatives often significant side effects iii Use of tamoxifen to decrease great cancer in high risk women 1 May increase cervical cancer risk balance risk Lecture 49 Sex Differentiation Male Reproductive System 1 Chromosomes 3 23 pairs 23 from mother 22 x and 23 from dad 22 x or y 2 5 b Carries genes which code for proteins i Vast majority of genes never get turned on ii Have 10000 unique genes c X and Y Chromosomes i XX is female ii XY is male iii X chromosome is large many genes iv Y chromosome is small few genes 1 SRY gene starts male development in utero v 106 male fertilizations100 female fertilizations 1 102 male births100 female births 2 More male childhood deaths because of problems with X chromosomes Gonads in Embryo a Gonads are the testes and ovaries b At 7 h week with SRY sex region Y gonadal medulla testes cortex regresses i Without SRY gonadal cortex ovaries medulla regresses dies off Puberty a Maturation of reproductive system i Females hair patterns breast development and menstruation ii Males hair patters erectile function sperm musculature b Onset i Increased gonadotropin in RH GnRH release from hypothalamus necessary kisspeptin stimulated triggers ovulation ii Increase release of FSH and LH from pituitary iii Leptin from adipose tissue may be necessary for menarche start of menstrual cycle Pituitary Gonadotropins a Need GnRH from hypothalamus for release b Controlled by negative feedback of gonadal hormones testosterone estrogen progesterone c FSH i Females growth and activation of ovarian follicles ii Males develop and mature sperm by activating sertoli d LH i Females ovarian maturation estrogen secretion ovulation ii Males testosterone secretion from levidig cells Testes a Seminiferous tubules sites of sperm production i Sertoli cells assist sperm production ii Leydig cells testosterone production Spermatogenesis Formation of sperm cells from spermatocytes 100 million spermday Sperm Formation i Spermatogonium mitosis one stays here one migrates inward 353 ii Migrating cell spermatocyte remodeled to sperm cell iii Sertoli cells absorb most of spermatocyte cytoplasm d Sperm Structure i Head acrosome digestive enzymes nucleus 23 chromosomes ii Midpiece mitochondria iii Tail propulsion by microtubule rotation 00 V LO V 1 Only needed to near ovum Temperature i Maximum sperm production at 32 degrees C body is 37 ii Scrotum will rise in cold and descend in heat to maintain temperature m V iii Nondescended testes are usually sterile Semen a Liquid holding sperm 3m Lejaculation 300000000 sperm b lt 20000 spermejaculate considered sterile c Accessary structures contribute fructose mucus clotting proteins bicarbonate semen d 1 in 6 couples are infertile most common reason is the male 1 Erection a Arteriole dilation venas compression 9 engagement b Parasympathetic n 9 no production 9 alternative vasodilation 2 Emission a One minute before ejaculation b Mixing of prostatic fluid sperm and seminal vesicle fluid just prior to ejaculation c Sympathetic n control emission 10 3 Ejaculation a Skeletal contraction expelling sperm 11 Testosterone Steroid hormone Released in utero shortly after birth to create male reproductive system No further release until puberty Tonic release thereafter Secretion 235 m V i From leydig cells as made in the testes ii 98 bound to protein in circulation iii 2 free and active iv Stimulates protein synthesis f Secondary Sex Characteristics i Male hair pattern ii Penile and genitalia enlargement iii Vocal cord thickening so their voice gets deeper iv Increased mental activity v Increased sex drive vi Increased growth Antibolic Effects i Growth spurt then epiphyseal closure Uh V ii Increased musculature and kidney size 12 Inhibin a Released from sertolicells b Inhibits FSH release c All hormones FSH LH testosterone inhibin are tonic and stable after puberty Lecture 50 Female Reproductive System 1 Menstrual Cycle a 2135 days variable 28 days is average b Some women are regular others are irregular c Ovum prepared for release from follicle d Uterus prepared for implantation of embryo 2 U V U39I V Ovarian Cycle a Ovum growth release follicular change b Follicular Phase i Days 114 dominated by FSH stimulation ii Several follicles enlarge and form antrum has estrogen iii One follicles outgrows others which regress in size atresia iv Estrogen released from granulosa and thecal cells surrounding ovum c Ovulation i 14 h day ii High levels of estrogen stimulate kisspeptin release from the hypothalamus iii Kisspeptin stimulates GnRH release which stimulates the lutinizing hormone LH surge iv LH from anterior pituitary ruptures antrum v Ovum released into abdomen fimbria sweep ovum into oviduct vi Ovum surrounded by granulose and thecal cells and zona pellucida vii Ovum moves down oviduct to uterus 5 days in transit d Luteal Phase i Days 14 28 ii Carpus luteal forms from remaining cells in ruptured follicles iii CL secreted progesterone and estrogen iv Progesterone prepares uterus for implantation Uterine Cycle Site of fetal growth Changes will supply implanted embryo with energy until placenta develops Proliferative Phase 352 Days 5 14 after the uterine line starts thickening Variable This is the phase that shifts if a woman is not regular Estrogen dominated Repair of uterine surface after menstruation Increased uterine lining thickness and blood supply Secretory Phase i Days 14 28 ii Uterine lining greatly increases vascularization and thickness iii Progesterone dominates P decreases uterine contractions iv Uterus secretes glycogen for embryo Menstruation i Days 1 5 ii Sloughing off of uterine lining if no implantation Cervix a Opening between vagina and uterus b Usually blocked with mucus prevents infection c Estrogen thins mucus and kills alkalizes secretions lets sperm in lessens acid killing of sperm i Progesterone thickens mucus Indicators of Ovulation iv v D V m V a Increase in basal body temperature by increase progesterone b Thinning of cervical mucus c Fertilization range 3 days 2 days before ovulation sperm life time to 1 day after ovulation fertilizable ovum Ovarian Hormones a Estrogen and progesterone have multiple effects b Estrogens i Formed from g and 39 quot from thecal cells ii Thecal and granulosa cells produce estrogen iii Effect of Estrogen 1 Increases follicular development inhibits FSH 2 Increases ciliary motion in oviducts increases uterine muscle size thins cervical muscle 3 Kisspeptin release at ovulation increase neural plasticity and increase sex drive Progesterone i Increase sections and size of uterus increase breast development ii Increase cervical mucus inhibits LH release 391 V iii Decline in progesterone causes increase in contractions during pregnancy increase heat production d Relaxin i Hormone is secreted from ovaries and placentainto the blood and directly into the oviduct ii Helps sperm penetrate ovum membrane iii Increases digestion of connective tissue iv Softens pelvis and cervix for delivery 7 Menopause 400 cycles in females 1400 of 7 million oocytes develop per cycle Only one ovum released the remaining undergo atresia Decline and loss of estrogen and progesterone when oocytes gone Osteoporosis 235 m V Decreased estrogen linked to osteoporosis 1 PTH Vitamin D Ca all normal ii Decrease in bone density iii Less effect when bones are thicker at menopause iv Weight bearing work and exercise thicken bones Cardiovascular Effects i Increases in cardiovascular disease after menopause ii Decreased HDL increased vascular reactivity with decreased estrogen iii Increase in blood pressure Hormone Replacement i High doses of estrogen designed to help decrease menopause symptoms such as hot flashes ii Recent links slight increase in heart disease stroke breast cancer iii balance riskbenefit v V Uh V Lecture 51 PregnancyLactation 1 Fertilization a In oviduct b Capacitation increase sperm motility occurs in female reproductive tract c Chemical attraction of sperm to ovum d Head of sperm attaches to zona pellucida on the egg receptors e Digestive enzyme in acrozone break down zona pellucida f Sperm enters ZP receptors blocked blocks second entry 2 Embryo Development a Ovum starts dividing after fertilization 9 blastocyst still surrounded by other cells 9form trophoblast b Takes 4 to 5 days for the developing embryo to reach the uterus still constantly dividing c Interuterus trophoblast implants in uterine wall become placenta d Folic acid needed for proper embryonic development 3 Corpus Luteum a Remnant of the ruptured follicle l V V V V b ICG from uterus maintains corpus luteum c Continues progesterone production until placenta large enough for progesterone production Placental Hormones a Function to maintain pregnancy b hCG i Human charianic ganadtropin ii Maintains corpus luteum after implantation iii Used for pregnancy tests high levels of hCG show up c Progesterone i Decreases uterine contractions during gestation ii Decrease in P triggers start of contractions at parturition d Relaxin i Also decreases uterine contractions ii Softens pelvis and cervix for delivery Placental Functions a Supply steroids for fetal cortisol b Exchange of gases nutrients waste products c Increase material respiration and renal output Parturition a quotChild birth b Exact imitator unknown c Increase estrogen 9 increase uterine excitability increase number of gap junctions and increase number of oxytocin receptors d Progesterone i Decreases in most cases ii iii Progesterone still high for women going into premature labor e Oxytocin i Oxytocin levels high throughout pregnancy but low number of receptors ii In some deliveries other factors overcome quieting effect of progesterone on uterus Increase number of receptors near term estrogen effect 1 Increase uterine contractions and cervical dilation f Labor i Positive feedback increase uterine pressure 9 oxytocin release 9 increase pressure 9 increase prostaglandin release 9 oxytocin induced contractions ii Spinal reflex aids delivery by increase abdominal contractions iii Head first then shoulders then rest of body then placenta afterbirth Lactation a Milk production for newborn nutrients b Prolactin PRL i Not a gonadotropin does not cause hormonal release ii iii PRL secretion peaks at parturition c Breast Development i Estrogen increases mammary duct size ii Progesterone increase mammary labule size iii PRL completes structural development d Milk Secretion i Primary by PRL ii Females milk secretion First two weeks are colostrum nutrients lacroferrin antibiotic antibodies Physiology 9232013 103900 PM LECTURE 1 o What is physiology 0 Functional anatomy o Organization 0 Molecules Assembly of Atoms Major molecules are Carbohydrates Lipids Proteins and Nucleic Acids 0 Cells Basic unit of life Use energy do metabolism remove waste 0 Tissues Collection of similar cells with same local function Term also used generally 0 Organs Collection of different tissues Carries out distinct functions in the body 0 Systems Collection of organs Controls major coordinated functions o Homeostasis 0 Internal Environment Interstitial fluid between and around cells 0 Negative Feedback When event X causes a change away from a set point and then response Y causes it to return to the set point Basis of homeostasis Example Blood pressure muscle reflexes 0 Positive Feedback Event X causes a change from one set point to another Rare but important Example blood clotting change of state LECTURE 2 o Cytosol 0 Liquid around Cell O O 0 High protein content Protein clusters organized enzyme pathways METABOLISM Liver does the most of this Thousands of reactions Structural proteins energy production enzyme storage and use of carbs and lipids PROTEIN SYNTHESIS Structure determined by genes mRNA from nucleolus codes for protein manufacturing in ribosomes RIBOSOMES Combinations of protein and RNA Free ribosomes make protein for use in cytosol Few or no modifications after productions Chaperonins help protein folding STORAGE Glucose chains are called Glycogen in muscles used for contraction Stored in liver for fuel between meals Store carbohydrates in glucose chains Ions used in the brain need glucose to function not fats Starch and cellulose are made of chains of carbs Endoplasmic Reticulum O O O O O Interconnected tube of membrane smooth and rough are connected Manufacture membrane and proteins to ship out Rough has ribosomes for protein synthesis Smooth manufactures membrane and fats ROUGH ER Ribosomes link amino acids Newly formed proteins threaded into lumen of ER New proteins move from rough to smooth ER SMOOTH ER Produces vesicles that transport new proteins to the Golgi apparatus Make fats o Golgi Apparatus O O O 0 Series of flattened membrane tubes Receives vesicles from smooth ER and modifies proteins Directs proteins to specific organelles or to the membrane Docking proteins on vesicles and destination membrane ensure proper delivery PROTEIN MODIFICATION Proteins in Golgi have amino acids removed or modified Sugars are added to proteins to modify them Proteins only work in specific shapes Chaperonins ensure proper folding EXOCYTOSIS Vesicles from Golgi with export proteins merge with membrane and dump contents When intercellular calcium content increases ATP is used to initiate exocytosis o Lysosomes O O O O 0 Contain digestive enzymes Merge with endocytotic vesicles Digest molecules down to useable size Example break proteins down into amino acids ENDOCYTOSIS Must occur to balance exocytosis Extra cellular molecules bind to receptors and trigger membrane in folding PEROXISOMES Contain antioxidants Destroy oxygen radicals Combine two oxygen radicals to end chain PHAGOCYTOSIS A cellular defense mechanism Enclose a whole dead cell or bacteria cell White blood cells will sacrifice themselves while fighting infection Pus is dead bacteria and dead white blood cells LECTURE 3 o Anaerobic Energy Production Glycolysis o Glycolysis no oxygen 0 In cytoplasm and in cell membrane 0 Glucose NAD 2 ATP NADH 2 Pyruvate 2 ATP 0 NADH Pyruvate NAD Lactate o Mitochondria Aerobic Energy Production 0 In double membrane of mitochondria outer membrane has larger pores o Krebs cycle inside the matrix of the inner membrane 0 ETC part of the inner membrane it uses oxygen 0 KREBS Aka TCA or citric acid cycle 7 reactions take place in mitochondrial matrix Pyruvate NAD FAD C02 NADH ATP FADH2 Fats enter at Acetyl CoA step Pyruvate is processed to get acetyl co A which goes into the cycle fats can be changed into co A to be used NAD goes in and is decarboxylated NADH and FADH2 is made both fuel the ETC 0 MITOCHONDRIAL INNER MEMBRANE Cytochromes from ETC on inner membrane 0 OXI DATIVE PHOSPHORYLATION o Vaults NADH donates electrons to ETS H follows and NAD gets recycled Concentration gradient is made by NADH s giving their H to fuel the reaction Electrons pass and H is pumped through cytochromes ATP is made on H return 30 ATP per pass Oxygen gains electrons water 0 Octagonal barrel shaped structures 0 May be involved with transport from nucleus to cytoplasm 0 mRNA and ribosomes are possible cargo o Cytoskeleton o Intercellular frameworks 0 Protein polymer filaments o MICROTUBULES Polymer of tubin Have positive and negative ends Help with cell stability transport along neurons transport of vesiclesorganelleschromosomes CiliaFlagella n Cilia Lung fallopian tubes Propels mucus Dynein drives microtubule twisting n Flagella sperm 0 INTERMEDIATE FILAMENTS Permanent load bearing filament in skin Maintains shape Smaller than tubules o MICROFILAMENTS Thin are moved by actin Thick are moved by myosin LECTURE 4 o Membrane Structure 0 Separates intercellular v interstitial fluids 0 Phospholipids make chemical and physical barrier o PHOSPHOLIPIDS Backbone of membrane Soap like properties HYDROPHOBICHYDROPHILIC a Fat soluble center of membrane a Hydrophobic molecules cross easily a Hydrophilic outsides a Flexible bilayer a Water soluble molecules have a hard time getting across 0 Cholesterol Interspersed between lipid portions of phospholipids Prevent close packing of fatty acids Hydrophilic OH group Create membrane uidity and flexibility Doctors say not too high but too low increases risk for cancer 0 Proteins Some mobile some restricted RECEPTORS a On outside of cell bind to solute chemical or ion a Activated by physical change a Activates channel or enzyme a Eye receptors activated by light waves CHANNELS a Only ions can pass specific channels for specific ions n Span throughout the membrane a Receptors open the channels a Channels for K Na Ca Cl ENZYMES n Catalyze reactions n Some initiated by receptors other are always active n Chop up viruses to digest them DOCKNG MARKER ACCEPTORS n Recognize and bind to secretory vesicles n Sites of exocytosis CARRIERS n Revolving proteins a Bind and move with gradient high to low concentrations a Use ion gradient for energy source 0 Ca rbo hyd rateProtein Complexes Identify self to immune system basis for separation of cells into tissues during embryonic development order of carbohydrates identifies by certain sequences limit normal tissue growth to confined region o Intercellular Connection 0 All cells have negative outsides o No cells actually touch but are tethered o CAM s CELL ADHESION MOLECULES Anchor cells to other cells or to basil lamina Maintain tissue integrity Abnormalities occur during metastatic cancer Control cell migration 0 Tight Junctions Block fluid movement between cells Prevents things from going between so molecules must go through cells Creates sidedness of tissue where there is a surface like on skin cells Skin intestines kidneys Allows selective transport water can barely move through them 0 Desmosomes Cellular rivets Strong connections that cant tear apart Polymers hold cells together Heart intestine skin uterine cells 0 Gap Junctions LECTURE 5 Channels between cells Ions pass as an electrical link Electrical signal from one cell activates the next cell Recoordinate contractions of the heartbeat when it gets off beat Contractions during birth Uterus heart bladder GI tract o Diffusion Across Membranes 0 Driven by chemical or electrical gradient 0 Simple diffusion cannels and carriers 0 Diffusion goes in all directions molecules are independent 0 Net diffusion is always high to low 0 HYDROPHOBICITY Fats and gases cross easily But its hard for them to get to the membrane because of charges Fluidity allows an 8 micron RBC to deform though a 7 micron capillary This enhances oxygen transport because oxygen is super close to the capillary wall 0 SIZE Small objects pass through more easily than large Fick s Law of Diffusion 0 Rate of diffusion 0 Q PA ACAX MW 0 Molecular weight as denominator means that larger weight means slower diffusion o Hydrophobic things pass easily while charged things do not Ion Channels 0 Different types for different ions 0 Allow ions to move from chemical and electrical gradients 0 Channels for Na K Ca and Cl Osmosis o Diffusion of water through a semi permeable membrane 0 Water moves from high water concentration to low Carrier Transport 0 Protein molecules change shape and let molecules move across the membrane Energy from concentration gradient or ATP SPECIFICITY Each carrier transports a specific molecule or type of molecule SATURATION Limited number of carriers in each cell When all carriers are being used the rate is at its max Transport max limits carrier mediated transport FACILITATED DIFFUSION No ATP used moves down concentration gradient 0 O O O Molecule binds to one side carrier reorients molecule leaves on opposite side More binding on high concentration side 0 ACTIVE TRANSPORT Uses ATP for energy to move ions against their concentration gradient Low to high Active transport creates gradients across cell membranes NaK ATPase a No life without this n Moves Na out of cells and K into cells n Na high on outside K high on inside a Creates gradient to allow electrical signaling 0 SECONDARY ACTIVE TRANSPORT Lamer has two binding steps agonist triggers response and Na Energy of Na gradient drives this Cotransport agonist in or countertransport agonist out Na transports some glucose and amino acids in this way In some tissues other ions drive this Pumps things out to create a gradient used in other reactions LECTURE 6 o Voltage 0 Separation of charge 0 Cells are negative inside positive outside 0 Opposite charges line up along membrane o Resting Membrane Potential 0 Voltage across cell membrane when cell is not activated 0 Determined by open ion channels 0 K dominates at rest most open channels 0 Na contributes a bit few open channels 0 Concentration Na is 150 mm in ECF and 15 mm in ICF in muscle K is 5 mm in ECF and 150 mm in ICF in muscle Protein is 0 mm in ECF and 65 mm in ICF in muscle Concentrations are different in different types of cells 0 Permeability Determined by number of open channels Number of open K or NA channels determine ion diffusion Different open number in different cell types 0 NaK ATPase Enzyme that creates gradients and restores them after ions diffuse across membrane Equilibrium Potential 0 Only open channels determine membrane potential 0 If cell is negative enough K wont flow at 90 o If cell is positive enough Na wont flow at 60 K Diffusion at Rest 0 At rest K channels are open 0 60 is the most possible for K PumpLeak Balance 0 Balance between pump and diffusion channel activity 0 Since ions will consistently diffuse down that gradient though channels a constant input of ATP into ion pumps is needed to maintain the gradient Resting MP Changes 0 MP changes in cells including muscle and nerve cells MP is ALWAYS negative at rest Less negative during depolarization More negative during hyperpolarization Depolarization Membrane potential is less negative Caused by K channels closing and Na opening MP moves toward Na equilibrium 0 Hyperpolarization More K channels open than Na channels 0 O O O o Graded potentials o Triggered by agonists or physical force 0 Size of potential is proportional to the size of the stimulus o Spreads to adjacent areas decays rapidly over time and distance 0 Occurs in many different cells LECTURE 7 o Action Potential 0 Like a tsunami Long range electrical signal in nerves and muscles Activated by a graded potential Don t degrade over time and distance VoltageGated Channels Will open when membrane reaches a voltage that is 15 to 20 more than resting potential All vgated channels open together o Phases of the AP 0 Depolarization Threshold Chemical or mechanical vgated Na channel open Na enters into the cell gets more positive At threshold all channels open 0 AP Spike All vgated Na channels open together and there is rapid depolarization Gets to about 20 mV Doesn t reach equilibrium though some K channels open 0 Repolarization Na channels close after 2 milliseconds K channels still open Potential falls 0 Hyperpolarization O O O O All K channels are open so potential falls below resting potential Doesn t reach K equilibrium at 90 0 Return to Resting Potential All extra K channels close o Neural Structure 0 Dendrites Receive neurotransmitter from neurons Many branches Only graded potentials here 0 Cell Body Cell organelles and nucleus Axon Hillock n Beginning of axon first place where action potential starts a High density of vgated Na channels 0 Axons Very long carry Action Potential away from cell body Speed of AP variable will increase with and increase of diameter and myelin Myelin B Cells that surround the axon n Insulated axon to prevent electrical loss a Increases action potential speed a Nodes of Ranvier o Spaces between myelin o Completes AP circuit Refractory Period a After vgated channels close they stay closed for 30 milliseconds a No new action potentials during this time n Action potentials only travel in one direction o Frequency of Action Potentials o All AP are identical in cells 0 Information is passed by the frequency not the size of AP 0 More AP stronger signal input to the CNS LECTURE 8 o Synaptic Structures o Presynaptic Neuron End of axon synaptic knob aka terminal button Receives the AP down the axon AP opens Ca channels on knob Vesicles n Contain neurotransmitter n Increase in Ca triggers merging with cell B NT clumped into cleft and diffuses to the post synaptic membrane 0 Postsynaptic Cell Has receptors for neurotransmitter from presynaptic neuron Receptors connected to ion channel Channel opens when NT binds to receptor EPSP Excitatory Postsynaptic Potentials 0 NT binds to receptor and Na channels open 0 Na enters and causes depolarization 0 One EPSP is not enough to reach threshold 0 Need 15 to 20 to reach threshold IPSP Inhibitory Postsynaptic Potentials o K or Cl channels open by NT 0 K leaves or Cl enters down electrochemical gradient 0 Membrane potential becomes more negative 0 Way less likely to reach threshold Grand Postsynaptic Action Potential Sum of EPSP and IPSP If threshold is reached AP is fired Most neurons are inhibited by IPSP s Axon Hillock Atjunction of cell body and axon High density of Na channels to start AP Oneway Conductance 0 NT are only release from presynaptic neuron receptors to the synapse to the post synaptic neuron 0 Information only goes one way 0 Temporal Summation O O O O EPSP from the same neuron close in time are additive Sum to reach threshold 0 Spatial Summation EPSP from different neurons all add up Sum to reach threshold Some neurons receive signals from 1000 s of other neurons o Convergence 0 Multiple synapses into a single neuron o Anatomical basis for spatial summation 0 Many dendrites are being stimulated from pre synaptic neurons o Divergence 0 Each axon is sending out many knobs to many different post synaptic neurons 0 An action potential in one neuron delivers neurotransmitter to all its divergent neurons at the same time LECTURE 9 o Paracrines 0 Local hormones 0 Released from one cell an affects the neighbor cell 0 Nitric Oxide important in control of blood cell s flow it relaxes blood vessels dies out quickly o Neurotransmitters 0 Specific each neuron has only one type of NT 0 Variable neural cell length NT work locally 0 NT released by exocytosis cell to cell synapse o Neural to neural muscle and endocrine cells 0 Rapid removal diffusion digestion reuptake o Endocrine o Hormones released from endocrine tissue Broad effects hormone released into blood to circulate Sent everywhere in the body Effects target cell receptors Endocrine means hormone release 0 O O O o Neurohormones 0 Released from neurons into the blood 0 Functions as other hormones 0 Receptor dependent o Parkinson s is a decrease in dopamine in basal nuclei o Hydrophilic Hormones 0 Cannot cross the membrane 0 First messenger o Rely on membrane receptor activation 0 Membrane proteins produce second messengers o Second messengers 0 Relay signals from receptors on the cell surface to target molecule inside the cell in cytoplasm or nucleus Made at membrane Internal activation mechanism started by hydrophilic O O hormones 0 Only cells with the proper receptors respond 0 cAMP Cyclic AMP ATP cAMP activate kinase add phosphate to molecules Kinase transfers phosphate groups to from high energy donors such as ATP to substrates by phosphorylation cascades amplify signals Individual hormonal effects in different cells 0 CGMP GTP cGMP Activated by Nitric Oxide Activates kinase Regulates metabolic processes and mediates actions of various hormones Causes release of intracellular calcium stores Calcium stored in sarcoplasmic reticulum a structure modified from endoplasmic reticulum Helps contract muscles o Calcium 0 Released from internal sarcoplasmic reticulum by IP3 Enter across cell membrane through Ca channels Binds to and alteres protein activity Cell to cell Ca signal produces coordinated cilia waves In gap junctions depolarization causes cardiac and smooth muscle contraction in adjacent cells by opening Ca channels actin and myosin contract o G Proteins 0 Timing proteins 0 Bind GTP increase activity until it converts to GDP 0 Regulate vesicle movement cytoskeleton growth vision and second messengers o Hydrophobic Hormones 0 Diffuse easily into cells 0 Need transport molecules in watery environment 0 Target cells have receptors to tell genes to turn on or off 0 Steroid hormones are extremely hydrophobic and go straight to plasma proteins 0 Nuclear Receptors Form an interface between hydrophobic hormones and genes Determine which genes are activated by hydrophobic hormones Variations in gene activation in different cells are the basis for side effects o NeuralEndocrine Comparisons o Neurons Coordinate rapid precise brief responses Electrical activity covers most distances Neurotransmitter diffusion is a short distance 0 Hormones Control long duration activities Slower response not directly to receptor More complex reactions Long duration binding of hormones O O O O LECTURE 10 CENTRAL NERVOUS SYSTEM o Organization 0 CNS Brain and spinal cord 0 PNS peripheral nervous system nerves that carry out information into and out of CNS o Afferent Neurons 0 Carry information into the CNS from PNS 0 Both conscious and unconscious info is carried o Efferent Neurons 0 Carry info from CNS to the body 0 Somatic NS neurons activate skeletal muscles 0 Autonomic NS Supplies neural input to organs Parasympathetic day to day homeostasis Sympathetic Emergency situations fight or flight o Interneurons o In the CNS more than 99 of all neurons 0 Perform all neural functions of the CNS thinking memory 0 Don t store facts in cells make connections instead 0 Cant do mitosis o Glial Cells 0 Nonneural support cells in the CNS 0 Capable of mitosis 0 Have cancer potential 0 Astrocytes Star shaped cells hold neurons in proper position Control neural grown and blood vessel growth in brain Blood vessel form a bloodbrain barrier by tight junctions around capillaries Repair injury and form scar tissue Degrade neurotransmitters and control extracellular K o Oligodendrocytes Form myelin sheaths around axons Limited neural growth in CNS 0 Microglia O O Immunity cells in CNS work like WBC Phagocytes move to area of infection or damage Uncontrolled activity may or may not be involved in neurodegenerative diseases Ependymal Cells Line brains ventricles and secrete cerebrospinal fluid Have cilia that circulate fluid Tight junctions control fluid release Cerebrospinal fluid absorbs shock Mary be able to differentiate into other glial cells Cancer Potential Glial cells divide so they can become cancerous Neural cells don t divide so they cant form cancers The large number of glial cell types makes diagnosis hard o Nutrition 0 O 0 Brain needs constant supply of glucose and oxygen to survive No glucose storage in brain need constant supply from blood Strokes reduce blood flow vessel blockage or breakage o Cortex O O O O O O 0 Upper part of brain cerebrum Heavily rigid makes up 80 of the brain Unique human qualities reside here Voluntary movement conscious thought language morals More information stored means more ridges Lobes Frontal Movement personality decisions judgment morals Parietal somatosensory touch perception proprioception position Occipital visual integration Temporal hearing and emotion long term memory Plasticity No mitosis of neurons learning involves making new synapses between existing neurons Practiced motor activity enlarges controlling area of the brain Areas grows larger because more neurons are involved If cortical input reduced areas will receive more input from adjacent areas If cortical area is damaged surrounding areas can pick up lost function 0 Language Control Left side of brain Connection of sounds and symbols with objects Broca s Area Speech formation cant form words spoken or written Wernicke s Area Temporal lobe comprehension of auditory or visual information cant comprehend what they re saying but can make sounds 0 Association Areas Higher brain functions association cortexes integrates multiple inputs Prefrontal association cortex controls planning morals personality ParietalTemporalOccipital association cortex makes coordinated world views links touch sight and sound 0 Hemispheres Right visual spatial relations aesthetics art Left Analytical processing and language analytical Geniuses use both use one side to relate it to the other 0 Electroencephalogram Records background electrical activity of the brain Used for death determination review session 9232013 103900 PM o Glycolysis anaerobic in cytoplasm or clusters on membrane 0 NAD goes in and NADH goes out 0 Take glucose apart to pyruvate and NADH pyruvate goes to o Krebs O O O O O O O Krebs NADH goes to ETC Pyruvate is processed to get acetyl co A which goes into the cycle fats can be changed into co A to be used NAD goes in and is decarboxylated NADH and FADHZ is made both fuel the ETC In inner mitochondrial matrix ETC oxidative phosphorylation Chemical gradient is stronger than physical Negative inside 10172011 115600 PM Lecture 11 Subcortical Structures 7 Memory gt Subcortical Structures 0 Structures below the cortex that control different function H v w a Collection of 5 structures on each side of brain i Below cortex to the sides of thalamus ii Connected to each other and cortex iii Postural control is nonconscious iv Feedback loops connect posture variations V Decreased dopamine linked to Parkinson s disease a Receives sensory input from the opposite side b Directs and edits input to cerebral cortex c About 98 of input blocked from reaching cortex d Cortical focus allows info through thalamus e One type of autism may be due to lack of thalamus editing Controls homeostatic functions a b Temperature thirst milk release hunger reproductive urges circadian rhythms increases emotional feelings c HT sees what is wrong makes no decisions i Cortex decides what to do gt Limbic System 0 Ring of structures underneath cortex of cerebrum o Detects emotions and memory formation 0 Hippocampus is part of limbic system a Feelings about things Fquot Reproductive drive rage fear motivation c Cortical decisions few connections to cortex i Limited cortical control of emotion d Can t make emotions just go away it takes time distractions e Cortical control is over responses i Limited input of limbic system to motor areas ii No compulsory action a Nonepinephrine dopamine and serotonin are NTs in limbic system b Altered concentrations of NTs have been associated with depression i Antidepresants use receptors for these NTs c Excess dopamine has been linked to Schizophrenia i Limits Ldopa Parkinson s treatment gt Memory 0 Retention storage and ability to recall information 0 Memory traces are sequences of neural activities I Declarative Memory I Facts events words language rules 0 Hippocampus and temporal lobe for storage I Procedural Memory unconscious I Physical skills habits and tasks I Cerebellum plays major role a Seconds to hours b Alter activity in existing neurons in hippocampus c Can be erased and replaced a Creation of new synapses and memory traces b Make multiple copies of important memories over years c Retain youthful memories as you age d Transfer from hippocampus to cortex a In the prefrontal association cortex b Compares newly acquired short term data and long term data c Determine relevance of new material organizes priorities a All amnesia is inability to recall I Retrograde Amnesia Caused by trauma I I Loss of short term memory I No long term memory formation of traumatic events I No long term loss nothing to recall later I Antero grade Amnesia D Hippocampal damage D Can t form new long term memories D Memory stuck on day of damage D Common with strokes Lecture 12 Cerebellum 7 Sleep 7 Spinal Cord gt Cerebellum 0 Structure on back of brainstem 0 Controls coordinated movements and learned movements a Connected to motor cortex receives motor plan b Afferent input gives current muscle position c Coordinates function with aim movement matches motor plan d As practice occurs motor cortex parietal lobe and cerebellum take over e Flaming is reduced initiation of activity is faster and smoother input to cortex a Allows cortex to know current position and movement b Cortex uses this information to plan future movements gt Brain Stem C Medulla pons and midbrain o Interference between spinal cord and higher brain centers 0 Cranial nerves supply sensory and motor functions to head and neck 0 Different centers in brainstem control heart rate breathing wakefulness gt Reticular Activating System 0 Neural net awareness of surroundings o Cortical pain auditory input 0 Output to cortex and thalamus all cortex 0 Controls consciousness and sleep gt Sleep 0 Low frequency activity in hypothalamus and thalamus sleep 0 Reason needed is unknown Slow wave patterns in EEG give slow wave sleep its name EEG pattern during REM sleep similar to being awake 1quot l p 4 stages each progressively deeper over about a 75 minute cycle Circadian rhythm high adenosine 7 sleep Caffeine blocks adenosine response Sleep factor 39 Muramyl dipeptide 7 strong sleep inducer e gt Spinal Cord o Neural tissue encased in verbal column 15 minutes long at end of slow wave sleep cycle Paradoxical Sleep i Hard to awaken most likely waken self High visual cortex low frontal high memory areas 7 dreams illogical New synaptic contacts made greater long term memory Will make up for missed REM sleep 0 Carries APs between brain and body 0 Grey matter in the middle A cell bodies and intemeurons 0 White mater on the outside A myelinated neuronal tracts Bundles of neural axons that carry APs Ascending tracts carry APs toward brain Entry points for afferent neurons to the spinal cord bilateral Afferent cell bodies are in the dorsal root ganglin gt Re exes l Carry efferent APs out of the spinal cord Cell bodies of efferent neurons in the grey matter 0 Neural responses without the conscious output a From receptor to afferent neuron to CNS to Efferent Neuron to Effector b CNS portion may have 1 or more synapses c Effectors are muscles and glands d Monosynaptic Re ex l synapse e Polysynaptic Re ex Multiple synapse f Interactions between afferent and efferent neurons a Polysynaptic re ex b Multiple neurons between afferent and motor neurons c Prolonged response and feedback d Very strong re ex but with potential CNS input l r V 1 n l a Muscle length information b Monosynaptic re ex knee jerk c Activation of afferent neuron produces re ex response through synapse to efferent neuron d No control by upper CNS Lecture 13 Afferent Nervous System 7 Pain 7 Taste Smell gt Sensory Receptors Sensation 0 Connect an environmental signal to body 0 Transduction is the conversion of a stimulus to a physiological signal 0 The brain converts the physiological signal into a perceived sensation gt Stimulus 0 Environmental signal 0 Binds and changes a receptor 7 signal now in body 0 Each receptor binds one stimulus best A Ex Hit in eye with ball 7 you see stars even though there are no stars gt Sensation o Conscious senses 7touch taste smell hear see and time o Unconscious 7 position temperature blood pressure changes gt Types of Receptors 0 Must bind stimulus 7 no dendrites on receptor cells ex Smell o Modified nerve endings to interact with stimulus a Physical changes open ion channels b Changes membrane potential c Touch receptors hair cells in ears photoreceptors baroreceptors a Taste and smell b Chemoreceptors 7 chemical binds receptors and opens ion channels i Changes membrane potential gt Receptor Potential Also called generator potentials local potentials graded potential Depolarization of receptor cells Size of potential proportional to size of stimulus Receptor elds vary in size depends on of afferent neurons 11 Pl a More stimulus greater receptor potential b In receptor cells without AP release of NT proportional to receptor potential a Continuous stimulus leads to larger generator potentials more APs to CNS b AP number translated by CNS as size of stimulus gt Adaptation Decreases AP number despite prolonged stimulus a Adapt overtime 7 rate is variable b Touch receptors adapt quickly c Pain BP receptors adapt slow a Virtually do not adapt b Few true tonic receptors smell gt Sensory Speci city gt Pain Normal stimulus produces a response that the brain interprets Different stimulus needs more strength for a response Brain still interprets as normal response 7 eX see stars Survival value protection from harm Anticipation of pain activates pain areas of cortex Nociceptors 7pain receptors chemical or physical a Sharp localized passes quickly Fast myelinated afferents 7 glutamate NT 31 a Diffuse dull long lasting w unmyelinated afferents 7 substance P NT a Presence suspected before discovery b NT unique to afferent slow pain receptors a Natural analgesics block pain by binding to opioid receptors b Activation alters ion channels and membrane potential A Enkephalins Endorphins I Peptides multiple types different sizes I Short halflife 25sec I Morphine 7 effective for hours gt Chemical Senses 0 Molecular binding to receptors 0 Flavor combination of smell and taste gt Taste 0 Molecules dissolve in saliva and reach taste bud receptors to be tasted a Receptors at taste pore b Tight junctions keep saliva away from rest of taste bud c Surrounding epithelial cells 7 basal cells 7 receptor cells d Turnover 10 days a Sensory neurons sent taste information b Neurons to thalamus 7 parietal lobe i wha taste c Neurons to limbic system i like it a Salty 7 Na b Sweet 7 organic sugars c Acid sour 7 H d Bitter bases quinine 7 cations poisons i Most sensitive receptor e Umami 7 glutamate MSG gt Smell o Olfactory mucus membrane on roof of nasal cavity 0 1000 different odor receptors largest gene family A 1 of human genome molecules must diffuse through mucus H20 soluble and bind to recpetor to activate must be volatile enough to oat to top of cavity l Part of dendrites of olfactory neurons E i Covered in mucus b Neurons turn over every few weeks c Unusual dendrites as receptors i New neurons mitosis a Unusual receptors primarily tonic b Unusual most adaptation in CNS i Brain can overcome adaptation Adaptation to ones smell does not effect others 0 Odors seem less strong after some time 3 1 Lecture 14 Vision gt Structure of the Eye 0 Designed to receive light and produce electrical signals to send to brain to produce 3D image a Clear noncellular front of eye Light passes through not refracted bent Fquot Lens refracts light to focus on retina a b Cilia body has muscles parallel to lens c Muscle contraction allows lens to round up focus near Muscles relax for distance vision 2 1 a Opens closes pupil b Smooth muscle c Contractions adjust to light level a Between cornea and lens i Constant production and drainage b Glaucoma less drainage or excess production 7 high pressure 7 retinal damage c Beta blockers have low production cholinergic agonists have high drainage a b Between lens and retina c Maintenance of eyeball shape d No refraction E Visual receptor at the back of the eye 6 Multiple cell layers a Highly pigmented layer behind retina Fquot Absorbs light 7 no re ection 7 no signal gt Refraction 0 Bending of light waves 0 Glycoproteins in lens refract light and focus it on retina gt Retina 0 Light passes through bipolar and ganglion cells to reach photoreceptor cells 0 Bipolar and ganglion cells pulled back at fovea o Fovea has best color vision D Dense cone concentration a Rods i Shades of grey ii Most photoreceptors b Cones i Color receptors ii Few overall receptors c Rods and cones produce receptor potentials No APs d Both converge on bipolar cells Mr C l ls a Generator potentials activated by rods and cones b No APs i Synapse with ganglion cells c Edge effect centersurround onoff effects W a R ach threshold and re APs the leave eye for CNS b Carry visual information to lateral geniculate part of thalamus 7 cortex gt Optic Nerve 0 Bundle of ganglion cell axons o Creates blind spot as axons pass through retina o Cortex lls in blind spot with expected image Il b Edits information to cortex a Multiple areas in occipital lobe b Integrates output of visual perception c Relative positions 7 3D image gt Accomodation 0 Change in lens thickness alters focal point for near and far vision 0 Ciliary muscles control focus 0 Thin lens far thick close 39j l v w a Lens gradually hardens over decades b Hardening reduces rounding of lens for near vision c At 4050 years old difficulty focusing on near objects d Need reading glasses bifocals u IrHV we a Inability to focus retina b Myopia nearsighted eyeball too long focus in front of retina c Hyperopia farsighted eyeball too short focus behind retina Corrective lenses or laser surgery on cornea 3 1 gt Rhodopsin Visual pigment in rod cells Combination of opsin and retinene Vitamin A derivative 0 Light hits retinene and partially splits it from opsin bleaching o Opsin now active 7 G protein system 7 releases NT from rod proportional to light 0 Retinene rebinds to opsins awaiting new light gt Color Vision 0 3 different opsins with retinene A Shading of retinene limits frequency range 7 peaks at red also sees yellow green and blue wavelengths a One opsin missing b Can t distinguish certain wavelengths with equal activation of remaining opsins Lecture 15 Hearing and Equilibrium gt Outer Ear 0 Little ampli cation 0 Direction detection a Overlapping membranes b Seperates outer and middle ears c Vibrates to external air waves gt Middle Ear 0 Air lled o Ampli es sound 20X a Maileus incus stapes b Hammer anvil stirrup c Carry waves from tympanic membrane to oval window 5 LJL315 juan l y liv a Drains middle ear of uid b Equalizes air pressure between middle ear and sinuses c Normally closed i If unopenable tubes needed in eardrum a Membrane that connects middle ear to inner ear gt Inner Ear o Fluid lled o Converts sound waves to electrical signals l 1 7 130 a Cochlea spinal shaped tube of inner ear b Organ of Corti part of cochlea that transduces sound to APs i Waves carried to apex and back to oval window ii Oval window absorbes all sound waves NO APs I Similar to choroid in eye a 391quot1l n39snle I Vibrates to sound waves I Shape change over length I High frequency to base low frequency at apex I Rest on basilar membrane I Hairs imbedded in tectorial membrane I Less movement I When basilar membrane vibrates imbedded hairs are pulled on I Hair cells produce GP 7 NT to different neurons APs to CNS by auditory nerve gt Frequency of Sound 0 Maximum range A 20 hz to 20000 hz 0 Lose high frequency hearing with age l a Overtones allow source distinction i Type of musical instrument or individual voice b Total signal fundamental frequency and overtunes gt Amplitude of Sound 0 Amplitude of sound 0 Height of sound wave 0 Higher wave more hair cell movement and more APs to brain gt Deafness 0 Loss ofhearing l L ijri4l1JJiiyy Sound waves don t reach hair cells a b Wax eardrum damage middle ear bone damage c Hearing aid helps i Amplify sound to vibrate oval sound directly a Damage to hair cells or auditory nerve b Need cochlear implant to treat c Frequency deafness i Loud repetitive sounds at one frequency pull out hair cells in one place selective hearing loss gt Equilibrium o Vestibular apparatus 0 Detect changes in motion 1139 nil1m m will 91 in 1 1 a 3 semicircular canals at right angles to one another b Fluid lled i As uid lays motion uid pulls hair cells I Hair cells imbedded in cupula I Inertia generates GP 7 AP L 1 E a Hair cells imbedded in gel with otoliths i Acceleration pulls on hair cells ii Gravity constant itonic signal know position of head I Detect linear acceleration I Utricle horizontal motion I Saccule vertical motion I Mismatch of signals 7 motion sickness excess rides or less space ight Lecture 16 Efferent Nervous System gt Sympathetic Structure 0 Part of the autonomic nervous system Sympathetic chain ganglia parallel to spinal cord Input from cord medulla hypothalamus o No direct cortical control 1 Preganglionic Neurons a Short neurons b Use Acetylcholine Ach as NT to postganglionic neurons in ganglia 2 Postganglionic Neurons a Long neurons b Activated by preganglionic neurons c Use norepinephrine NE as NT d Adrenal medulla behaves like postganglionic neuron gt Sympathetic Responses 0 Responds to emergencies l FightorFlight Response a Designed to remove danger b High blood ow to skeletal muscle and heart c Concurrent activation of motor units d Low activity of digestive and related functions 2 Receptor Types a Adrenergic receptors b All bind NE from postganglionic neurons 0 Alpha Adrenergic Receptors I Alpha 1 7 high 1P3 7 high Ca release from sympathetic response 7 high Ca I Alpha 2 7 low cAMP 7 low Ca pump 7 net high Ca 0 Beta 1 Adrenergic Receptors I Increase Ca in heart 7 open Ca channels I Increase in heart activity 0 Beta 2 Adrenergic Receptors I High cAMP 7 high Ca pump 7 low Ca I Low blood vessel contraction and low lung bronchiole construction more blood more air gt Parasympathetic Structure 0 Port of autonomic nervous system 0 Two neuron sites 7 all neurons use Ach as NT 0 Cholinergic activation controls daytoday homeostatic maintenance 1 Preganglionic Neurons a Long neurons i Spinal cord to organ b Synapse at ganglia or organs with postganglionic neurons 2 Postganglionic Neurons a Short neurons i Travel from ganglia to cells gt Parasympathetic Responses 0 Decrease in heart rate 0 Increase GI contractions and secretions 0 Increase pancreatic secretions o Contractions urinary bladder o Relaxes internal anal and urinary sphincters gt AgonistsAntagonists o Pharmaceuticals can mimic or antagonize autonomic NS 0 Parasympathetic higher or lower digestive activity etc o Sympathetic high BP in shock low BP in hypertension gt Motor Neurons 0 Alpha motor neuron gets multiple inputs 7 up to 10000 0 Input from stretch receptors withdrawl re exes cerebellum learned activities cortex conscious control 0 Both IPSPs and EPSPs to alpha motor neurons 7 Threshold 0 1 AP in motor neuron 1 AP in muscle neuron gt Neuromuscular Junction NMJ 0 Motor neuron synapse with skeletal muscle ber cell 0 Motor end plate very large synapse l Acetylcholine Release a Presympathetic AP 7 Ca entry 7 Ach release b Ach binds to receptors on muscle membrane 2 Endplate Potential a EPP is larger than EPSP b Ach binds receptor 7 high Na entry threshold c 1 motor neuron AP leads to 1 muscle AP 3 1 control of motor neuron APs controls nuscle activation 3 Acetylcholinesterase 7 AchE a AchE degrades Ach to choline and acetic acid b Reuptake of choline diffusion away of acetic acid 4 NM Poisons a Inhibit diaphram can t breathe i Black widow spider venom 7 releases all Ach ii Botulinum toxin 7 blocks Ach release iii Curare 7 blocks Ach receptors Lecture 17 Muscle Structure and EC Coupling gt Striated Muscle Structure 0 Skeletal connects to 2 tendons 7 tendons attach to bone 0 Cardiac smaller cells 7 attached endtoend 1 Muscle Fibers a Cell ber b Runs length of muscle in skeletal muscle c Changes size thickness but no mitosis 2 Striations a Lines skeletal and cardiac muscle b Due to laments lined up in register c Filaments overlap 7 overlap more during muscle contractions A Dark and Light Bands I Dark bands contain thick laments may also have thin laments I Light bands only have thin laments NO thick laments B Sarcomere I Unit of contraction zline to zline I Thin laments are anchored to zlines I Thick laments connect to thin laments during contraction I What one sarcomere does all do C Thin Filaments I Actin polymer backbone 7 double stranded helix I Tropomyosin long thin protein polymer runs along actin I Troponin binds to tropomyosin D Thick Filaments I Myosin polymer of lamentous protein I Extension of myosin is crossbridge I Crossbridge head can bind to actin E Ttubules Sarcoplasmic Return I Ttubules invaginations of muscle membranes carry APs into muscle ber interior I Sarcoplasmic Return develops from ER stores Ca I Connected to ttubule by voltage sensitive protein I AP down the ttubule opens Ca channels in the SR Excitation Contraction Coupling 0 Electrical events leading to muscle contraction l Skeletal Actin Potential a Starts at NMJ synapse b NT Ach binds to receptor and opens Na channels and starts AP spread in both directions N Release of Calcium a At ttubule AP travels inward and alters protein in ttubule i Leads to opening Ca channels in SR near ttubulin I Ca released b Ca pumps at far end of SR resequesters i Ca and causes relaxation 3 TroponinCalcium Binding a Ca binds to troponin on thin lament 4 Tropomyosin Shift a Ca bound to troponin causes tropomyosin to shift into actin groove exposing actinmyosin binding site 5 ActinMyosin Binding a Actin and Myosin connect b Myosin already has ATP bound and converted to ADPPi with ADPPi still bound to myosin head A Force Generation I ADPPi released 7 myosin shape changes and head twists leading to force development I No sliding I Pi release is key to force development B Filament Sliding I Filaments slide to decrease force on crossbridge head goes to lowest energy state Force 0 I New ATP binds to myosin and actin is releases D Process repeats as long as Ca is elevated gt Relaxation Cessation of APs stops Ca release from SR Calcium pumps return released Ca to SR Tropomyosin reblocks Actinmyosin binding site Muscle relaxes Lecture 18 Skeletal Mechanics gt Motor Unit 0 Motor neuron and muscle bers it innervates 0 Motor neuron AP activates all the bers in a motor neuron 1 Recruitment a Small motor neurons rst then larger b Allows gradiation of force c Mazimum force requires all motor neurons active simultaneously 2 Asynchronous Recruitment a For submaximal forces rotate activation of all motor neurons b Maintain force cannot simultaneously optimize force and continuous activity gt Twitch 0 Single muscle activation 0 l neural AP 7 1 muscle AP 7 l twitch o submaximal force not enough Ca4 reaches all troponin for full activation gt Tetanus o Summation of all twitches many APs o Enough Ca so that all myosin heads reach actin 0 Max force muscle can produce gt Length Tension Relation 0 L0 muscle length at which maximum force occurs 0 Resting skeletal muscle length is near L0 1 Falloff at Long Lengths a Reduce overlap of thick and thin laments 2 Falloff at Short Lengths a Thick laments compression against zline b Thin laments overlap and interfere with each other c Reduced Ca release gt Force Velocity 0 Heavy loads can only be moved slowly 0 Light loads are moved quickly 1 Inverse Relation a High force load 7 low velocity b Low force load 7 high velocity 2 Stretched Muscles a Stretching before activation windup uses top of LT curve b Better force maintenance c Activating stretch re exes 7re eX contraction of stretched muscle A Power Curve I From FV curve I Power F X V I At F0 P0 At V0 P0 I All others F X V is positive must have maximum I 025 F0 has optimal power output I stretching active muscle can hold 7 15x F0 before yielding I muscles resist being stretched more than the force they can generate Lecture 19 Muscle Metabolism and Control gt Muscle Energy Use 0 Progressive use of energy resources 1 Phosphocreatine a Supports about 20 sec of full activity b PCr ADP 7 ATP Cr by creatine kinase reaction c ATP 7 ADP Pi by myosin ATPase d PCr 7 Cr Pi net reaction e Pi inhibits myosin ATPase i MADPPi 7 M ADP Pi 2 Glycolysis a 10 reactions generates ATP more slowly b c d 72 min of energy use Glucose and glycogen in muscles 7 pyruvate 7 lactate No oxygen use 3 Oxidative Phosphorylation a b 9 D gt Fiber Types Also knows as Krebs Cycle and electron transport system 72 hours of energy support Pyruvate 7 C02 Oxygen used Carbohydrate loading increases glycogen storage increase up to 30 0 Variations in ber type even within same muscle 0 Controlled by motor neuron most muscles are mixed 1 Red Fibers a b C Also called slow oxidative High mitochondria levels 7 slow myosin i ATPase 7 slow speed High energy capacity low energy use 7 no fatigue 2 White Fibers a b C gt Hypertrophy Also called fast glycolytic Few mitochondria 7 fast myosin ATPase 7 fast speed Low energy capacity 7 high energy use 7 easily fatigued 0 Larger cells not hyperplasia more cells 0 High intensity high force exercise needed for maximum effort 1 Filament Number a b C d C High intensity exercise causes microdamage to filaments Disassembly of tangled filaments increases free myosin and causes pain Free myosin causes increase in expression of filament forming enzymes 7 more filaments bigger cells Young 48 hour cycle 24 disassembly 24 assembly Elderly 72 hour cycle 2 Testosterone Dependence a b gt Atrophy Filament production optimized by testosterone Females with normal hormones cannot maximize muscle size 0 Reduction in size of muscle bers 0 Not loss of of bers 1 Disuse a Muscle immobilized 7 loss of laments b Easily reversible 2 Denervation a Motor neuron damage 7 ber loss lament b Mot reversible 7 loss of myotrophic factor from neuron c Electrical stimulation cannot prevent atrophy gt Stretch Re ex Muscle length information Monosynaptic re ex knee jerk Activation of afferent neuron produces re ex response No control by upper CNS 1 Muscle Spindles a Stretch receptors in muscles b Groups of intafusal bers in connective tissue capsule 2 Intrafusal Fibers a Each muscle contains muscle section and stretch receptor section Fquot Fibers activate afferent neurons to CNS from receptor section of ber Fibers also receive efferent gamma motor neuron to muscle section of ber A Nuclear Bag Fibers I Have larger central portion of receptor 0 D Dynamic Response Detects change of length Highest response when muscle rapidly stretched Decreased response as stretch is sustained Rapid adaptation B Nuclear Chain Fibers I Smaller set of receptors parallel to nuclear bag bers D Static Response 0 Detects ber length 0 Response proportional to position 7 slow adaptation C Gamma Motor Fibers I Efferents to intrafusal bers I Contract muscle portions of intrafusal bers D Coactivation 0 Dual activation of alpha and gamma motor neurons 0 Alpha motor neurons contract muscle bers 0 Gamma motor neurons contract intrafusal bers 0 Keeps muscle spindles taut gt Reciprocal Innervation 0 Inhibition of paired muscle When stretch re ex occurs 0 Afferent neuron 7 intemeuron 7 IPSP to paired alpha motor neuron gt Golgi Tendon Organ Muscle force detectors Receptors in tendon 7 afferent input proportional to muscle force At very high forces GTO sends IPSPs to alpha motor neurons Protective effect Lecture 20 Smooth Muscle gt Smooth Muscle Structure 0 Small cells linked by desmosomes o No striations o Filaments parallel but not in register 1 Filaments a Thin laments actin and tropomyosin no troponin b TM in groove no AM blocking 2 Dense Bodies a Smooth muscle equilivent to zlines b Anchored to cell membrane all in interior c Thin laments attach here and pull ends out of cell gt Tone 0 Force with no stimulus o Ca leaks in and partially activates smooth muscle 0 Important in BP maintenance holding cavity contents gt Smooth Muscle Contraction 0 Different control mechanism than striated muscle 0 Ca also activates 1 Calcium Sources a Most through channels across cell membrane b Some small SR released by 1P3 2 Myosin Light Chain Kinase a Ca activated b Adds phosphate to myosin light chains c Activate myosin ATPase for shortening and force 3 Force Generation a MyosinADPPi with MLCP bind actin b Myosin twists generates force c Filaments slide to reduce force d This part similar to striated muscle 4 Myosin Light Chain Phosphatese a MLCPase removes phosphate from myosin light chains b Turns off myosin and causes relaxation when Ca is low gt Latch 0 Removal of Pi from light chain when AM attached decreases M detachment rate 0 Maintains force with little energy use 0 Allows BP maintenance with low energy use allow upright position gt Smooth Muscle Types 0 Vary with function empting cavities or maintaining force 1 Visceral Single Unit SM a If one contracts they all contract b Use APs linked by gap junctions c Phasic activity stomach d Random contractions small interval e Most shorten to empty cavity f Open sodium channel 7 move toward threshold A Neural Effects I Parasympathetic release Ach cause contraction I Sympathetic release NE cause relaxation 2 MultiUnit SM a Each cell is individually active no APs or gap junctions b Get average force large blood vessels eye muscles A Tone I Very important I Small force with latch 7 low energy cost to maintain BP I Force can go up or down from tone level B Neural Effects I Sympathetic receptor dependent I Alpha open Ca channels increase concentration I Beta 2 increase Ca pump activity decrease contraction 10172011 115600 PM Ll intro to Physiology Thursdav August 29 2013 1230 PM What is Physiology 0 Functional anatomy 0 Dynamic processes maintaining or moving to a control set point Organization 0 Each level built on the one below Chemical level Cellular level Tissue level Organ level The stomach Body system The digestive system Molecules Assembly of atoms Major physiological ones are proteins carbs lipids and nucleic acids Cells Cell is basic unit of life Uses energy has metabolism removes waste Tissues Collection of similar cells with same local function Term also used generally such as quotlung tissuequot Organs Collection of different tissues Carries out distinct function in the body Systems Collection of organs Controls major coordinated functions Respiration circulation etc Homeostasis 0 Maintain the normal physiological state 0 internal environment lnterstitial fluid Liquid around cells 0 O O O O o Negative Feedback common EventX causes a change away from state set point Response Y causes a return to set point Basis of homeostasis Examples blood pressure ion concentrations muscle reflexes 0 Positive Feedback rare but important EventX causes a change to a new set point state change No return to original set point Examples blood clotting parturition No protein in blood leads to swelling ie Swollen abdomen in starving people Parturition child birth L2 Cell Structure Thursday August 29 2013 1230 PM Cytosol 0 Liquid portion high protein content 0 Protein clusters organized enzyme pathways enhance metabolism Metabolism 0 Thousands of reactions 0 Enzymes are protein catalysts 0 Structural proteins energy production enzymes storage and use of carbohydrates and lipids Protein Synthesis 0 Chains of connected amino acids 0 Structure determined by gene 0 mRNA from nucleus codes for protein manufacture on ribosomes Ribosomes o Combinations of protein and RNA 0 Free ribosomes make proteins for use in cytosol 0 Few or no modifications after production 0 Chaperones help protein folding Storage 0 Glycogen is polymer of glucose in muscle for use during contraction in liver to maintain blood glucose between meals Some in many other tissue Endoplasmic Reticulum 0 Long series of tubes interconnected Smooth and rough ER Site where proteins are manufactured Manufacture membranes Rough ER Covered in ribosomes rough Manufacture proteins Ribosomes link amino acids Newly formed protein threaded into ER lumen as it is made New proteins move through ER to smooth ER Smooth ER Manufacture membranes Produces vesicles that carry new protein to Golgi Apparatus 0000 O Norwboxome Fat o Goxgmpparatu AkocaHedGo ngomp ex Senexof attened embranetube Recervewende R non thh new protem to pea c organeHe ortne eH memorane Dockmg protem on vemde and dextmatwon memorane emure properdehve Protem modrncatron Protem m GA have ammo add removed or modrned Sugar aread e em and modmed Protem on y o p hape tnerrappropnatexnape cnap r hatprotemxfmd propeny Exocytom vende mergmg w an 1 Re u t uxame rze 39 Protem to ammo acwd nydrate to monoxacchande Endocytom urto ba ance exocytom ExtraceHu armo ecu e omd receptor andtnggermemorane mfo dmg Peroxoome 7 many reamon Contam antroxrdant Dextroy oxygen radxca 40 of energy m body uxed to contract muxde 40 uxed m ron tramportatwon Bram on y uxe g ucoxe forenergy LuerceH make more drtferent enzyme tnan aH otherceH myour body Oooa Protem m 00 Rrboxorne L3 7 Energy Production Cyloxkelelon m r m Sumembe n3 n TP AdenoxmenPnPnP o CeHu armoney o x AZTP egt XVP ADP gtltrP na cuvrtytnat doe not eroorc Energ Producnon e G yco ym e no Oxygen n ytop axm free ATP and Cs membrane ATProrron pump o 2 ATPg ucoxewwt out ox gen o G ucoxe NAD z ADP DH z pyruvate 2 ATP o NADH pyruvate egt NA o w r Ana 9 Rx 7gtNA D actate recyde NAD n e ou Whatcomexmw atgo Lanownatrt uerwor MtochondrwanRerobwc nergyProdu r o D b e embranext tu o Outermembrane a arge re o Tom demmdematnxo nnermembrane o E ectron tramportxyxtem part ofthe mnermembrane me oxygen o P ruvate gtrnrrocnondna o d CrtncAcro Cy e rne a TCA yde Kreb Cyde n mwtochondna matrwanene of7 Rx Pyruvate NAD FAD egt 02 ATP NADH FADHZ F t nrerartneAcetyPCoxxtep o MrrocnononaxnnerMernorane Cytochrome form eectrontranportytern on mnermembrane o Oxroanye Phoxp oryxanon NADH donate e ectron to Us H foHoW NAD recyded A e paxxex H pumped at 3 Cytocnrornex ATP made on H return e H oxygen egt H20 uxe o nha ed oxygen z 573 ATPNAB w 572 ATPFADHZ 30 ATPg ucoxe Vaum o Octagona barre mapedxtructure o Maybe mvohed m tramport from tne nudeu to tne ytop axm o mRNA and rwboxome are pomb e cargo Cytoskeleton o lntracellular frameworks 0 Protein polymer filaments of different size and function 0 Microtubules Polymers of tubulin have and ends Cell stabilitytransport along neurons move vesicles organelles and chromosomes Movement Kinesin carries cargo along microtubules in direction toward membrane dynein moves cargo in direction toward nucleus Taxol anti cancer drug binds to and stabilizes MTs kills dividing cells Cilia Flagella Cilia lung oviducts dynein drives MT twists propels mucus ovum Flagella propel sperm into ovum rotary movement lntermediate Filaments Permanent load bearing filaments in stressed cells skin Maintain shape Shape maintaining scaffolding type structures Microfilaments Thin filaments actin polymer Thick filaments myosin polymer Movements in muscle and XBC39s Responsible for muscle contraction Like pressing two decks of cards together becomes shorter but wider ase at end of word means it39s an enzyme L4 Membrane Structure Thursday September 05 2013 1254 PM Membrane Structure 0 Separates lntracellular fluid lCF from lnterstitial Fluid lF 0 Physical and chemical barrier o iPhospholipid molecule 0 Phospholipids Backbone of membranes Head groups always have a charge on them negatively charged in phospholipids Hydrophilic Tail regions are made of fatty acids and are neutral Hydrophobic Soap like Fluidity within membrane and as a whole Two rows facing opposite directions One row with heads toward lnterstitial Fluid one with heads toward lntracellular Fluid Separates the two HydrophobicHydrophiiic Fat soluble center of membrane Hydrophobic molecules cross easily Hydrophilic outer sides of membrane iSeparation of ECF and lCF by the lipid bilayer 0 Cholesterol interspersed between lipid portions of phospholipids Prevents close packing of fatty acid chains Create membrane fluidity flexibility 0 Proteins in membranes Some mobile some restricted Receptors on outside Bind to solute either chemical neurotransmitter hormone drug or ion Some are activated by physical change touch Activate either channel or enzyme Channels Only ions go through Protein channels span membrane open or closed Specialized by ion type l Na Ca Cl Receptors open channels Enzymes Catalyze reaction A gtB Some activated by receptor some always active Docking marker acceptors Recognize and bind to secretory vesicles Sites of exocytosis Carriers quotRevolvingquot proteins no ATPase Alternate open side 2 types Molecules move with gradient Co transport with ion usually Na Use the ion gradient for energy source L5 Membrane Transport Tuesday September 10 2013 807 PM Diffusion Across Membranes 0 Driven by chemicalelectrical gradients Simple diffusion channels amp carriers Diffusion goes in all directions Net diffusion will always go from Up to Down Hydrophobicity Fats amp gases diffuse easily Fluidity allows 8 microns RBC39s to deform through 7 micron capillaries enhances OZ transports Small objects pass through more easily than large objects Xater can get through Not sugar protein aa Fick39s Law of Diffusion rate of diffusion O o O PHAdeltaCdeltaxlMW P permeability hydrophobicity hydrophilicity A area deltaCdeltaX concentration gradient Bigger faster MW molecular weight size Bigger slower movement lon Channels 0 Different types for different ions Na l Ca Cl 0 Allow ions to move by chemicalelectrical gradients Osmosis the diffusion of water 0 Water moves from high water concentration to low water concentration 0 Semi permeable membranes allow water to cross but nothing else Carrier Transport 0 Protein molecules change shape in membranes and move molecular across Energy for transport may come from gradient or from ATP Specifity Each carrier transports a specific molecule or type of molecule Saturation There are only a limited number of carriers in each cell When all carriers are being used the rate will be at a maximum The transport maximum limits carrier mediated transport Facilitated Diffusion No ATP used move down diffusion gradient Molecules bind to one side carrier reorients molecules leave on opposite side more binding on upincreasing concentration side High gt low Active Transport use ATP to move ions against gradient Low gt high 0 O O O O lons move from high affinity side to low affinity side Affinity likelihood to bind AT produces the ion gradients across cell membranes Na K ATPase Moves Na out of cells moves K into cells K is high inside cells not as high outside cells Creates gradients that allow electrical signaling 0 Secondary Active Transport Carrier has 2 binding sites agonist and Na Energy of the Na gradient out to in drives SAT Co transport against in or counter transport against out Na transports some glucose and amino acids in this way in some tissues other ions drive SAT L6 Membrane Potential Tuesday September 10 2013 857 PM Voltage separation of charge 0 All cells have a negative charge inside compared with lF o The opposite charges line up along the membrane 0 MP is always in the mV range MP membrane potential Resting Membrane Potential 0 Voltage across cell membrane when the cell is not activated Determined by open ion channels K dominates at rest Most open channels Some Na contribution few open channels Concentration Na is lSOmM in ECF l5mM in lCF in muscle K is 5mM in ECF lSOmM in lCF in muscle Protein is OmM is ECF 65mM in lCF in muscle lntracellular of Na l amp protein are different in different types of cells Permeability Determined by the number of open channels of open K and Na channels determine ion diffusion Different open in different cell types Produces different MP Na K ATPase This enzyme creates the and restores them after ions diffuse across the membrane this is ion pump activity Equilibrium Potential limits on K and Na Xhat voltage balances chemical gradient Only open channels determine MP 60mV Na all 0000 70mV Most K Few Na 90mV K all K Diffusion at Rest At rest K channels are open K diffuses out intracellular protein A is trapped in the cell Na channels are mostly closed little Na diffusion PumpLeak Balance There is balance between pump and diffusion channel activity Since ions will constantly diffuse down their gradients through channels a constant input of ATP energy into ion pumps is needed to maintain the gradients Resting MP Changes The membrane potential will change in many cells including nerve and muscle cells The MP always is negative at rest The MP magnitude decreases gets less negative during depolarization The MP increases gets more negative during hyperpolarization Graph of membrane potential of Depolarization decrease in potential membrane less negative Repolarization return to resting potential after depolarization Hyperpolarization increase in potential membrane more negative Resting potential Depolarization The membrane potential is less negative as from 70 to 60 mV Caused by K channels closing Na channels opening Hyperpolarization The MP gets more negative as from 70 to 80 mV Caused by K channels opening Na channels closing MP moves toward K equilibrium potential L7 Neurons Wednesday September 11 2013 1239 PM Neural Structure 0 Receive and pass on signals 0 Dendrites Receive neurotransmitter from other neurons Many branches O O O O O No action potential here only graded potentials Cell Body Cell organelles nucleus Axon hillock at beginning of axon high density of V gated Na channeb Action Potential starts here Axons Very long carry AP away from cell body Speed of AP variable up with up diameter and with myelin Myelin Nodes of Ranvier Cells surround axon and wrap layers of membrane Electrically insulates axon prevent electric loss to lF lncreases AP speed Nodes of Ranvier Spaces between myelin completes AP circuit APjumps between Nodes of Ranvier Refractory Period After V gated channels close they are unopenable for a time 30 200msec No new Aps during this time limits AP frequency AP only travel along axon in ONE direction can39t go back Frequency of Action Potentials All APs are identical in a given cell information is passed by the frequency not the size of action potentials More APs create a strong signal input to the CNS L8 Synapses Thursday September 12 2013 Synaptic Structures 0 O O O Neural neural synapses Presynaptic neuron End of axon synaptic knob terminal button Receive AP down axon AP opens Ca channels Vesicles Contain neurotransmitter up Ca triggers merger with cell membrane NT dumped into cleft diffuses to post syn membrane Postsynaptic Cell Has receptors for NT from pre syn neuron Receptors connected to ion channels Xhen NT binds to receptor channels open Excitatory Post Synaptic Potentials EPSPs