Class Notes Entire Semester - PSL 250
Class Notes Entire Semester - PSL 250 PSL 250
Popular in Introductory Physiology
verified elite notetaker
Popular in Physiology
This 125 page Bundle was uploaded by Danielle Lynch on Monday August 17, 2015. The Bundle belongs to PSL 250 at Michigan State University taught by Dr. Patrick Dillion in Fall 2015. Since its upload, it has received 102 views. For similar materials see Introductory Physiology in Physiology at Michigan State University.
Reviews for Class Notes Entire Semester - PSL 250
Report this Material
What is Karma?
Karma is the currency of StudySoup.
You can buy or earn more Karma at anytime and redeem it for class notes, study guides, flashcards, and more!
Date Created: 08/17/15
Mitochondria lysosomes Vacuoles I Cellmembrane I Cytoplasm L1 Introduction to Physiology Levels of Organization Homeostasis Golgi Bodies Endoplasmatlc reticulum Ribosomes What is Physiology Functional Anatomy Dynamic Processes maintaining or moving to a control set point Organization Each level built on the one below Molecules Assembly of atoms Major physiological ones are proteins carbohydrates lipids and nucleic acids Cells The cell is the basic unit of life Uses energy has metabolism removes waste Tissues Collection of similar cells with the same local function The term also is used generally such as lung 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 Maintain the normal physiological state Internal Environment Interstitial uid Liquid around cells Gets the energy it needs Projects wastes Negative Feedback common Event X causes a change away from state set point Response Y causes a return to set point Examples blood pressure ion concentration muscle re exes Positive Feedback rare but important Event X causes a change to a new set point state change No return to a set point Examples blood clotting parturition child birth death L2 Cell Structure Cytosol Liquid portion high protein content Protein clusters organized enzyme pathways that enhance metabolism Metabolism Thousands of reactions Enzymes are protein catalysts Structural protein energy production Enzymes storage and use of carbohydrates and lipids Carry out protein synthesis faster Protein Synthesis Chains of connected amino acids Structure determined by genes MRNA from nucleic acid codes for protein manufacture on ribosomes Spontaneous folding Ribosomes Combinations of protein RNA Free ribosomes make proteins for use in cytosol Few or no modifications after production Chaperones help protein folding Most proteins are made on ribosomes in the cytoplasm Storage Glycogen is a polymer of glucose In muscle for use during contraction In liver to maintain blood glucose between meals In many other tissues Endoplasmic Reticulum Complex of interconnected membrane tubules Production of exported or organelle proteins Rough ER Have ribosomes that link amino acids Site of protein synthesis Newly formed protein threaded into ER lumen as it is made Smooth ER Produces new membrane complex lipid molecules cholesterol No ribosomes Manufactures fats Membrane synthesis Produces vesicles that carry new protein Directs vesicles with new protein to Golgi Apparatus specific organelles or the cell membrane Golgi Apparatus Series of attened membrane tubes Receive vesicles from the ER Docking proteins on vesicles and destination membrane to ensure proper delivery Site of protein modification Protein Modification Proteins in GA have amino acids removed or modified Sugars are added to proteins and modified identified you are you in the immune system Proteins only work in specific shapes Most proteins naturally fold into their appropriate shape Chaperones ensure that proteins fold properly Exocytosis Vesicles from GA with export proteins merge with membrane and dump contents An increase in intracellular CA calcium triggers exocytosis ATP needed Lysosomes lysis something is broken or cut Contain digestive enzymes Merge with endocytotic vesicles Digest molecules down to usable size Proteins to amino acids Complex carbohydrates to monosaccharides Endocytosis Must occur to balance exocytosis Extracellular molecules bind receptors and trigger membrane in folding Puss is a collection of white blood cells Bacteria or dead cells trigger phagocytosis Peroxisomes Takes care of radicals something with one electron by making them in H202 Many reactions Liver cells are most versatile of all cells have most reactions Contains antioxidants Vitamin C amp Vitamin E also do this outside cells Destroys oxygen radicals very reactive destroys protein function HO H0 9 HOOH hydrogen peroxide ZHOOH 9 ZHZO 02 by the enzyme catalase fastest enzyme known L3 Energy Production Cytoskeleton ATP Adenosine P P P Cellular money X ATP 9 XP ADP Pphosphate XP has activity that X alone does not Anaerobic Energy Production No oxygen In cytoplasm free ATP and cell membrane ATP for ion pumps ion channels 2 ATP glucose without oxygen Glucose NAD ADP 9 10 RXS 9 NADH 2 pyruvate 2ADP NADH pyruvate 9 NAD lactate recycle NAD Lactic Acid9 Lactate H Mitochondria Aerobic Energy Production Double membrane structure Outer membrane has large pores TCA Cycle inside matrix liquid filled space of inner membrane Electron Transport System makes ATP part of inner membrane uses oxygen Pyruvate mitochondria Citric Acid Cycle Krebs Cycle TCA or citric acid cycle your body breaks down fats In mitochondria matrix 7RXs by 2 carbons at a time amp need oxygen Pyruvate NAD FAD COZ ATP NADH FADHZ Fats enter at the AcetylCoAstep 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 eH proton oxygen H20 use of inhaled oxygen 253 ATPNADH 152 ATPFADHZ 30 ATPglucose take NADH and FADHZ and take out hydrogens at each step eventually you take those hydrogens and oxygens and make water Vaults Octagonal barrel shaped structures May be involved in transport from the nucleus to the cytoplasm MRNA and ribosomes are possible cargo Cytoskeleton Intracellular frameworks Protein polymer filaments of different size and function All below help structure of the cell Microtubules think of railroad tracks 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 Anticancer drug binds to and stabilizes microtubules kills dividing cells Cilia Flagella Cilia in the lungs and oviducts Dynein drives MT twists propels mucus ovum Propels sperm into ovum rotary movement Intermediate Filaments Structural Permanent load bearing filaments in stressed cells skin Maintain shape Microfilaments Involved in muscles Thin filaments actin polymer Thick filaments myosin polymer Movements in muscle and WBC s white blood cells L4 Membrane Structure Membrane Structure Separates Intracellular uid ICF from interstitial uid IF Physical and chemical barrier Fats stick together and that s what separates the watersoluble parts Phospholipids Backbone of membranes Soaplike fatty tail and a charged phosphate head both oils and lipids can interact Fluidity within membrane molecules can move around in phospholipids and as a whole through capillaries Hydrophobic hating water Hydrophilic liking water Hydrophobic Fatsoluble center of membrane Hydrophilic molecules cross easily HPhils don t cross by diffusion except H20 High water solubility due to small size water molecules are smaller than the phospholipids Cholesterol Interspersed between lipid portions of phospholipids Prevents close packing of fatty acid chains Create membrane uidity exibility Proteins In membranes Some mobile some restricted Receptors lock On outside Bind to solute either chemical neurotransmitter key hormone drug or ion Some are activated by physical change touch Active either channel or enzyme Channels Only ions go through Protein channels span membrane Open or closed Specialized by ion type Kpotassium Nasodium Cacalcium Cl chloride Receptors open channels Enzymes Catalyze reaction A93 Some activated by receptors some always active Docking marker Acceptors Recognize and bind to secretory vesicles GA Sites of exocytosis Carriers quotRevolvingquot proteins no ATPase Alternate open side Sugars and fatty acids can move through 2 types 1molecules move with gradient from high concentration to low 2cotransport revolving doors with ion usually Na Carbohydrate Protein Complexes Identify self protects you to the immune system Basis for separation of cells into tissues during embryonic development Limit normal tissue growth to confined region keep your tissues in the right place Intercellular Connections Proteins and large structures CAMs Cell Adhesion Stick Together or to surface Molecules Proteins Anchor cells to other cells or to basal lamina noncellular surface Maintain tissue integrity keep things in the right place Abnormalities occur during metastatic spreading cancer Control cell migration Tight Junctions things between cans Block movement between cells Create tissue sidedness Skin intestines kidneys Allows selective transport molecules must go through cells Ex It s on skin digestive system intestines kidneys Desmosomes Cellular rivets Hold moving cells together skin heart Gap Junctions Channels between cells ion pass electrical link coordination Electrical signal from one cell activated next cell Heart G1 tract bladder uterus L5 Membrane Transport Diffusion Across Membranes Driven by chemical or electrical gradients Simple diffusion channels and carriers Diffusion goes in all directions Net diffusion will always go from high to low Hydrophobicity Fats and gases cross easily Fluidity allows 8micron red blood cells to deform through 7micron capillaries enhances oxygen transport Size Small objects pass through more easily than large objects Sugar amino acids proteins cannot get through the membrane Fick s Law of Diffusion skiing how fast does something go Rate of diffusion Q Q P A change in C change in x MW P Permeability Hydrophobic cross membrane easily Sticky vs icy Hydropholicity cross membrane not easily A Area thickness of the membrane Crowded hill Change in C concentration changes Change in x distance stays constant concentration gradient Big drop vs shallow drop MW Molecular weight size Force of gravity Ion Channels Different types for different ions Na K Ca Cl Allows ions to move by chemical their concentration electrical their charge gradients Outside and inside of cells have opposite gradients charges They attract each other Osmosis The diffusion of water Water moves from high water concentration low solute other stuff concentration to low water concentration high solute other stuff concentration Semipermeable membranes allow water to cross but nothing else baseball story Carrier Transport Protein molecules change shape in membrane and move molecules across Energy for transport may come from concentration gradient or from ATP Specificity Each carrier transports a specific molecule or type family 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 Tm limits carrier mediated transport Facilitated Diffusion No ATP used move down diffusion gradient Molecules bind to one side carrier reorients molecules leaves on opposite side more binding on high concentration side Movement from high to low concentration Active Transport Use ATP for energy to move ions against their concentration gradient Movement from low to high concentration Ions move from high affinity side to low affinity side AT active transport produces the ion gradients across cell Membranes Ion active transports low level to high is an ion pump NaK ATPase Moves Na out of cells moves K into cells K is high inside cells Na is high outside cells Creates gradients that allow electrical signaling Secondary Active Transport Carrier has 2 binding sites agonist and Na Energy of the Nagradient out to in drives SAT Cotransport agonist in or countertransport agonist out Na transports some glucose and amino acids in this way In some tissues other ions drive SAT secondary active transport L6 Membrane Potential Voltage Voltage Separation of charge All cells have a negative charge inside compared with interstitial uid The opposite charges line up along the membrane MP is always in the mV millivolt range Resting no active signal Membrane Potential Voltage across cell membrane when the cell is not activated Determined by open ion channels K dominated at rest most open channels Some Na contribution few open channels Concentration Na is 150 mM in ECF 15 mM in ICF in muscle K is 5 mM in ECF 150 mM in ICF in muscle Protein is O in ECF 65 in ICF in muscle The intracellular concentrations of Na K and protein are different in different cell types Permeability Determined by the number of open ion channels The number of open K more negative MP or Na more positive MP channels determines ion diffusion Different open number in different cell types Produces different resting MP NaK ATPase This enzyme creates the gradients and restores them after ions diffuse across the membrane this is ion pump activity Equilibrium Potential limits on K and Na What voltage balances chemical gradient Only open channels determine MP 60 70 MP of neurons 90 mV equilibrium for K Na Most K open K All Few Na open All K Diffusion at Rest At rest K channels are open K diffuses out Intracellular protein A is trapped Na channels are mostly closed little Na diffusion Pump Leak 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 goes toward 0 during depolarization The MP increases gets more negative during hyperpolarization Depolarization The membrane potential is less negative as from 70 to 60mV Caused by K channels closing Na channels opening MP moves toward Na equilibrium potential Hyperpolarization Increase in potential membrane more negative as from 70 to 80 mV Caused by K channels opening Na channels closing MP moves toward K equilibrium potential Graded Potentials Receptor Potentials short distances Triggered by agonists chemical binding to a receptor or by physical force Size proportional to the size of the stimulus Spreads to adjacent areas but decays rapidly Can only carry a signal over short distances Occur in many cells types receptors neurons and muscles In neurons and muscle GPs needed to reach threshold of Action Potentials L7 Neurons Action Potential Action Potential long distances Electrical signal long range in neurons and muscle Activated by graded potentials AP s do not degrade over time and distance Voltage Gated Channels Will open when membrane reaches particular voltage Usually 1520 mV above resting potential All v gated channels open together causing action potential Enter inactivated state soon after opening making refractory period Phases of the AP Controlled by different open channels Depolarization to Threshold Chemical or mechanicalgated Na channels open Na enters down gradient Tthreshold At t all Vgated Na channels open TTX blocks fast Vgated Na channels AP Spike Since all Vgated Na channels open together all APs in one neuron are identical Na enters rapid depolarization to 20 mV Doesn t reach Na equilibrium potential because some Vgated Kchannels also open Repolarization Vgated Na channels close after 12 msec K channels still open K leaves membrane potential falls Hyperpolarization Voltage goes below resting because extra K channels are still open Nearer to 90 mV K equilibrium potential than at rest Return to Resting Potential Extra K channels close Neural Structure Receive and pass on signals Dendrites Receive neurotransmitter from other neurons Many branches No action potential here only graded potentials Cell Body Cell organelles nucleus Axon hillock at beginning of axon high density of Vgated Na channels Action Potential starts here Axons Very long carry AP away from cell body Speed of AP variable increase with increase diameter and with myelin Myelin mostly made of fats cell membrane Cells surround axon and wrap layers of membrane Electrically insulates axon prevent electric loss to IF Increases speed Nodes of Ranvier Voltagegated K amp voltage Na channels Spaces between myelin completes AP circuit AP jumps between Nodes of Ranvier Refractory Period Na After Vgated channels close they are unopenable for a time 30200 msec No new APs during this time limits AP frequency AP only travel along axon in ONE direction can t 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 stronger signal input to the CNS L8 Synapses Synaptic Structures Neuralneural synapses Presynaptic neuron End of axon aka synaptic knob terminal button Receive AP down axon AP opens Ca channels Vesicles Contain neurotransmitter Ca more on out then inside the cell triggers merger with cell membrane NT dumped into cleft diffuses to post syn membrane Postsynaptic Cell Have receptors for NT from presyn neuron Receptors connected to ion channels When NT binds to receptor channels open Excitory Postsnaptic Potentials EPSPs NT binds and Na channels open Na enters and causes depolarization One EPSP is not enough to reach threshold Inhibitory Postsynaptic Potentials IPSPs K or Cl channels opened by NT K leaves or Cl enters down their electro chemical gradient Membrane potential more negative Less likely to reach threshold Grand Postsynaptic Action Potential Sum of all EPSPs and IPSPs Reach threshold Yes 9 fire AP Most neurons are inhibited by IPSPs most of the time Axon Hillock At the junction of the cell body and the axon High density of Vgated Na channels Action Potential starts here Oneway Conductance NT is only released from presynaptic neuron receptors only on postsynaptic neuron Information only goes in one direction Temporal Summation EPSPs from the same neuron close in time are additive they may sum to reach threshold Spatial Summation EPSPs from different neurons are additive The sum of these may reach threshold Some neurons receive synapses from 1000 s of other neurons Convergence Multiple synapses into a single neuron Anatomical basis for spatial summation Divergence Each axon has many synaptic knobs terminal buttons to other neurons An AP in one neuron delivers neurotransmitter to all its divergent neurons at the same time L9 Intercellular Communication Communication Types Communication between cells over short and long distances Combinations of electrical and chemical activity Paracrines Local hormones Released from one cell affects nearby cell Nitric Oxide Important in control of blood ow Neurotransmitters Specific each neuron has only one type of NT Variable neural cell length NTs work locally as released NTs released by exocytosis synapse cellto cell Neural to neural muscle endocrine cells Rapid removal diffusion digestion reuptake Endocrine Hormone released from endocrine tissue endothelial origin skin cells Broad effects hormone released into blood Goes everywhere Neurohormones Released from neurons into the blood Functions as other hormones receptor dependent Hydrophilic Hormones Cannot cross the membrane Rely on membrane receptor activation Membrane proteins produce second messengers Second Messengers Made at membrane Internal activation mechanism started by hydrophilic hormone 15t messenger Only cells with receptors respond cAMP Cyclase Adenosine MonoPhosphate ATP9 cAMP activate kinases add phosphate to molecules Kinase cascades amplify signals Individualized effects in different cells cGMP GTP 9 cGMP activates kinase 1P3 Causes release of intracellular Ca stores Ca stored in sarcoplasmic reticulum a structure modified from endoplasmic reticulum Calcium Released from internal sarcoplasmic reticulum by 1P3 Enters across cell membrane through Ca channels Binds to and alters protein activity Cellto cell Ca signal produces coordinated cilia waves exocytosis Gap junctions depolarization causes cardiac and smooth muscle contraction in adjacent cells by opening Ca channels G Proteins Timing proteins Bind GTP 9 increase activity until GTP 9 GDP Regulate vesicle movement cytoskeleton growth vision 2nd messengers Hydrophobic Hormones make new proteins Diffuse easily into cells Need transport molecules in watery environment Steroids Thyroid Hormone Vit A Vit D Increase protein synthesis by activating genes Widespread actions go into nearly every cell in your body significant side effects Nuclear Receptors Form interface between hydrophobic hormones and genes Will determine which genes activated by hydrophobic hormones Variations in gene activation in different cells basis for side effects Neural Endocrine Comparisons Neurons coordinate rapid precise brief responses Electrical activity covers most distance NT diffusion distance small Hormones control long duration activity slower responses More complex reactions long duration binding of hormones L10 Central Nervous System Organization The CNS is the brain and spinal cord The peripheral NS is the nerves that carry information in and out of the CNS Afferent Neurons Afferent neurons carry information into the CNS Both conscious and unconscious information is carried Efferent Neurons Carry information from the CNS to the body Somatic NS neurons activate skeletal muscles The Automatic NS supplies neural input Sympathetic and Parasympathetic to most organs The Para sympathetic NS oversees daytooday homeostasis The Sympathetic NS responds to emergencies Interneurons In the CNS more than 99 of all neurons Perform all the neural functions of the CNS thinking emotions memory etc Glial Cells Nonneural support cells in the CNS Capable of mitosis have cancer potential Astrocytes Starshaped hold neurons in proper physical positions Control neural growth and blood vessel growth in the brain Bloodvessel form bloodbrain barrier tight capillaries small pores between cells Repair brain injuries and form scar tissue Degrade neurotransmitters glutamate and GABA and control extracellular K Oligodendrocytes Form myelin sheaths around axons Limit neural growth in the CNS Microglia Immunity cells in the CNS Phagocytes move to areas of infection or damage Uncontrolled activity may or may not be involved in Ependymal Calls Line the brain s ventricles and secrete cerebrospinal uid CSF absorbs shock May be able to differentiate into other glial cells and possibly neurons Cancer Potential Because glial cells can divide they may become cancerous Neural cells do not divide and can t form cancers The large number of glial cell types and subtypes makes diagnosis difficult Nutrition Brain needs a constant supply of glucose and oxygen to survive No glucose storage needs constant blood supply Stroke storage needs constant blood supply Stroke reduces blood ow vessel blockage or breakage Cortex Upper part of the brain the cerebrum Heavily ridged 80 of brain Unique human qualities reside here Voluntary movement conscious thought language morals Lobes 4 Major Divisions of the Cortex Frontal movement control personality decisions moral judgment Parietal somesthetic touch perception and proprioception position Occipital visual integration Temporal hearing emotions Plasticity No mitosis of neurons but learning involves making new synapses between existing neurons Practiced motor activity enlarges controlling area of brain Area grows larger more neurons involved If cortical input reduced areas receive input from adjacent areas If cortical area damaged adjacent areas can sometimes pick up lost function Language Control Connection of sounds and symbols with objects Broca s Area in frontal lobe Speech formation Deficit difficulty forming words spoken or written Wernicke s Area in temporal lobe Comprehension of auditoryvisual information Deficity can form sounds but they contain no content Don t know what self 1s say1ng Association Areas Higher brain functions association cortexes integrate multiple inputs Prefrontal AC controls planning morals Parietal temporal occipital AC makes coordinated worldview links touch Sound and sight Hemispheres Right side visual spatial relations aesthetics Left side analytical processing and language Genius uses both Electroencephalogram Background electrical activity of the brain Recording on surface used for death determination Parietal Home Lobe Cranium Occipital Temporal Lobe 2009 WebMD LLC TO profronra Right LON codex Internal Bands 0 Thalamus Thalamus medunary myolinated lamina axons Cerebellum lntralaminar nuclei W Anterior Mediodorsal nuaei Hypothalamua mtemal Nucleus modullary v lamina TO auditory correx Pulvlm Geniculate 80 Contmm Lateral modmum TO motor Geniculate comcos Body TO somawsensory codex TO VJ39SuaI conox TO posterior association CONOX L11 Subcortical Structures Memory Subcortical Structures Structures below the cortex that control different functions Basal Nuclei Ganglia Collections of five structures on each side of the brain Below cortex to the sides of thalamus Connected to each other and to cortex Postural control is nonconscious Feedback loops correct posture variations Decreased dopamine linked to Parkinson s disease Parkinson s movements slow speech slow no loss of mental ability Thalamus Receives sensory input from the opposite side Directs and edits input to cerebral cortex About 98 of input blocked from reaching the cortex Cortical focus allows information through thalamus One type of autism may be due to lack of thalamic editing Hypothalamus Controls homeostatic functions Temperature thirst milk release hunger reproductive urges circadian rhythms increases emotional feelings HT sees what is wrong cortex decides what to do Limbic System Ring of structures underneath cortex of cerebrum Detects emotions and memory formation Hippocampus is part of limbic system Emotions Feelings about things Reproductive drive rage fear motivation Cortical Decisions Few connections to cortex limited cortical control of emotions Cant make emotions just go away takes time Cortical control is over responses limited input of limbic system to motor areas no compulsory action Neurotransmitters Norepinephrine Dopamine and Serotonin are NTs in the limbic system Altered concentrations of NTs have been associated with depression anti depressants Excess dopamine has been linked to Schizophrenia limits L Dopa Parkinson s treatment Memory Retention storage and ability to recall information Memory traces are sequences of neural activations Declarative Memory facts events words language rules hippocampus and temporal lobe for storage Procedural Memory Unconscious physical skills habits tasks Cerebellum plays major role Short Term Memory Seconds to hours Alter activity in existing neurons in hippocampus Can be erased and replaced Long Term Memory Creation of new synapses and memory traces Make multiple copies of important memories over years Retain youthful memories as you age Transfer from hippocampus to cortex Working Memory In the PreFrontal Association Cortex Compares newly acquired short term data and stored long term data Determine relevance of new material organizes priorities Amnesia All amnesia is inability to recall Retrograde Amnesia RA caused by trauma loss of shortterm memory No longterm memory formation of traumatic events No LT loss nothing to recall later Anterograde Amnesia Hippocampal damage can t form new LT memories No loss of previous LT memory Memory stuck on day of damage L12 Cerebellum Sleep Spinal Cord Cerebrum Structure on back of brainstem Controls coordinated movements and learned movements Balance Maintains balance and controls eye movements Coordination Connected to motor cortex receives motor planquot Afferent input gives current muscle position Coordinates function with aim ie movement matches motor plan As practice occurs motor cortex parietal lobe and cerebellum take over Planning is reduced initiation of activity is faster and smoother input to cortex Input to Cortex Allows cortex to know current position and movement Cortex uses this information to plan future movements Brain Stem Medulla pons and midbrain Interface between spinal cord and higher brain centers Cranial nerves supply sensory and motor function to head and neck Different centers in brainstem control heart rate breathing wakefulness Reticular Activating System RAS Neural net awareness of surroundings Cortical pain auditory visual input Output to cortex and thalamus 9 all cortex Controls consciousness sleep Sleep Low frequency activity in hypothalamus thalamus sleep Reason needed unknown EEG Patterns Slow wave patterns in EEG give slow wave sleep its name EEG pattern during REM sleep similar to being awake Slow Patterns 4 stages each progressively deeper over about 75 minutes cycle Circadian rhythm V adenosine sleep Caffeine blocks adenosine response Sleep factor muramyl dipeptide strong sleep inducer REM Rapid Eye Movement Paradoxical Sleep 15 minutes long at the end of a slow wave sleep cycle Paradoxical sleep hard to awaken most likely to wake self High visual cortex low frontal high memory areas dreams illogical New synaptic contacts made quotquot long term memory Will make up missed REM sleep Spinal Cord Neural tissue encased in vertebral column Carries APs between brain and body Gray matter in the middle cell bodies and interneurons White matter on the outside myelinated neuronal tracts Tracts Tracts are bundles of neural axons that carry APs Ascending tracts carry APs toward the brain Descending tracts carry APs from the brain to efferent neurons Dorsal Roots Entry points for afferent neurons to the spinal cord bilateral Afferent cell bodies are in the dorsal root ganglia Ventral Roots Carry efferent APs out of the spinal cord Cell bodies of efferent neurons in the gray matter Re exes Neural response without a conscious input Re ex Arc Receptor afferent neuron CNS efferent neuron effector muscle or gland CNS portion may have 1 or more synapses Effectors are muscles and glands Monosynaptic Re ex 1 synapse Polysynaptic Re ex Multiple synapses Interneurons between afferent and efferent neurons Withdrawal Re ex Polysynaptic re ex Multiple neurons between afferent and motor neurons Prolonged response and feedback Very strong re ex but with potential CNS input Stretch Re ex Muscle length information Monosynaptic re ex knee jerk Activation of afferent neuron produces re ex response through synapse to efferent neuron No control by upper CNS L13 Afferent Nervous System Pain Taste Smell Sensory Receptors Sensation Connect an environmental signal to the body Transduction is the conversion of a stimulus to a physiological signal The brain converts the physiological signal into a perceived sensation Stimulus Environmental signal Binds and changes a receptor signal now in body Each receptor binds one stimulus best Sensation Conscious senses 5 senses also time Unconscious position temperature BP changes Types of Receptors Must bind stimulus no dendrites on receptor cells exc Smell Modified nerve endings to interact with stimulus Physical Physical changes open ion channels Changes membrane potential Touch receptors hair cell in ears photoreceptors baroreceptors blood pressure Chemical Taste smell Chemoreceptors chemical binds receptors Opens channel changes mp Receptor Potentials Also called generator potentials local potentials Depolarization of receptor cells Size of potential proportional to size of stimulus Receptor fields vary in size depends on number of afferent neurons Magnitude More stimulus greater receptor potential In receptor cells without AP release of NT proportional to RP Frequency Dependence Continuous stimulus larger GPs more APs to CNS AP number translated by CNS as size of stimulus Adaptation Decrease AP number despite prolonged stimulus Phasic Receptors Adapt over time rate is variable Touch receptors adapt quickly Pain BP receptors adapt slowly Tonic Receptors Virtually do not adapt few true tonic receptors smell receptors Postural receptors in trunk are near tonic Sensory Specificity Normal stimulus produces a response that the brain interprets Different stimulus needs more strength for a response Brain still interprets as normal response see quotstarsquot Pain Survival Value Protection from harm Anticipation of pain activates pain areas of cortex Nociceptors pain receptors chemical and physical Fast Pain Sharp localized passes quickly Fast myelinated afferents glutamate NT Slow Pain Diffuse dull long lasting Slow unmyelinated afferent substance P NT Substance P Presence suspected before discovery NT unique to afferent slow pain neurons Opioid Receptors Natural analgesics block pain by binding to Opioid receptors Activation alters ion channels and membrane potential EnkephalinsEndorphins Peptides multiple types different sizes Short halflife 25 sec Morphine Effective for hours Chemical Senses Molecular binding to receptor Flavor combination of smell and taste Taste Molecules dissolve in saliva and reach taste bud receptors to be tasted Taste Buds Receptors at taste pore Tight junctions on the edge of the taste bud to keep saliva away from rest of taste Surrounding epithelial cells basal cells 9 receptor cells Turnover 10 days Neural Tracts Sensory neurons send taste information Neurons to thalamus parietal lobe what taste Neurons to limbic system like it Taste Receptors Salty Na Sweet organic sugars Acid sour H Bitter bases quinine cations poisons most sensitive receptor Umami glutamate MSG Smell Olfactory mucus membrane on roof of nasal cavity gt 1000 different odor receptors Largest gene family gt 1 of human genome Molecules must diffuse through mucus H20 soluble and bind to receptor to activate Must be volatile enough to oat to top of cavity Olfactory Receptors Part of dendrites of olfactory neurons covered by mucus Unusual dendrites as receptors new neurons Olfactory Adaptation Unusual Receptors primarily tonic Unusual Most adaptation in CNS brain can overcome adaptation Adaptation to one smell does not affect others L14 Vision Superior rectus m uscie A choroid sclera retina 39 fovea I r 39 optic nerve posterior chamber anterior chamber cornea aqueoos humor co munctiva inferior rectus muscle Structure of the Eye Designed to receive light and produce electrical signals Cornea Clear noncellular front of the eye Light passes through not refracted Lens Ciliary body Lens refracts light to focus on retina CB has muscles parallel to lens Muscle contraction allows lens to round up focus near Muscles relax for distance vision Iris Openscloses pupil Smooth muscle contractions adjust to light level Aqueous Humor Between cornea and lens constant production and drainage Glaucoma decrease drainage or excess production increase pressure retinal damage Beta blockers decrease production cholinergic agonists increase drainage Vitreous Humor Gellike bulk of eye volume Between lens and retina maintenance of eyeball shape Retina Visual receptors at the back of the eye Multiple cell layers Choroid Highly pigmented layer behind retina Absorbs light no re ection no signal Refraction Bending of light waves Glycoproteins in lens refract light focus it on the retina Retina Light passes through bipolar and ganglion cells for each photoreceptor cells Bipolar and ganglion cells puller back at fovea Fovea has best color vision dense cone concentration Photoreceptors Rods shades of gray most photoreceptors Cones color receptors fewer overall receptors Rods and cones produce receptor potentials no APs Both converge on bipolar cells Bipolar cells Generator potentials activated by rods cones No APs synapse with ganglion cells Edge effect center surround on off effects Ganglion cells Reach threshold and fire APs that leave eye for CNS Carry information to lateral geniculate part of thalamus 9 cortex Optic Nerve Bundle of ganglion cells axons Creates blind spot as axons pass through retina Cortex fills in blind spot with expected image Lateral Geniculate Receives information from ganglion cells Edits information to cortex Visual Cortex Multiple areas in occipital lobe Integrates input of visual perception Relative positions 3D images Accommodation Change in lens thickness alters focal point for near and far vision Ciliary muscles control focus Presbyopia Lens gradually hardens over decades Hardening reduces rounding of lens for near vision At 4045 years old difficulty focusing on near objects Reading glasses bifocals Myopia Hyperopia Inability to focus on retina Myopia nearsighted eyeball too long focus in front of retina Hyperopia far sighted eyeball too short focus behind retina Corrective lenses laser surgery on cornea Rhodopsin Visual pigment in rod cells Combination of opsin and retinene Vitamin A derivative Light hits retinene and partially splits it from opsin bleaching Opsin now active G protein system recycles 14 sec System changes membrane potential releases NT Retene rebinds to opsins awaiting new light Color Vision 3 different opsins with retinene Shading of retinene limits frequency range Peaks at red also sees yellow green and blue wavelengths Color Blindness on x chromosome One opsin missing Can t distinguish certain wavelengths with equal activation of remaining opsins L15 Hearing and Equilibrium Outer Ear Little amplification Direction Detection Tympanic Membrane Eardrum Overlapping membranes Separates outer and middle ears Vibrates to external air waves Middle Ear Air Filled Amplifies sound 20x Ear Bones Malleus incus stapes Hammer anvil stirrup Carry Waves from tympanic membrane to oval window Eustachian Tube Drains middle ear of uid Equalizes air pressure between middle ear and sinuses Normally closed if unopenable tubes needed in eardrum Oval Window Membrane connects middle ear to inner ear Inner Ear Fluid filled Converts sound waves to electrical signals Cochlea Organ of Corti C spiral shaped tube of inner ear 0 of C part of cochlea that transduces sound to APs Waves carried to apex and back to round window Round window absorbs all sound waves no APs Similar to choroid in eye Basilar Membrane Vibrates to sound waves shape change over length High frequency at base low frequency at apex Hair Cells Rest on basilar membrane Hairs imbedded in tectorial membrane Tectorial Membrane Where How big Much stiffer than basilar membrane less movement When BM vibrates imbedded hairs pulled on Hair cells produce GP 9 NT to afferent neurons APs to CNS by auditory nerve Frequency of Sound Maximum range 20 HZ to 20000 Hz Lose high frequency hearing with age Timbre Overtones allow source distinction Types of musical instruments or individual voice Total signal fundamental frequency overtones Amplitude of Sound Height of sound wave higher wave more hair cell movement and more APs to brain Deafness Loss of Hearing Conductive more common Sound waves don t reach hair cells Wax eardrum damage middle ear bone damage Hearing aid helps amplify sound to vibrate oval Nerve Dearness Damage to hair cells or auditory nerve Need Cochlear implant to treat Frequency deafness loud repetitive sounds at one frequency pull out hair cells in one place selective hearing loss Equilibrium Vestibular appaparatus detect changes in motion Rotational Acceleration 3 semicircular canals at right angles to one another Fluid filled as uid lags motion uid pulls on hair cells Semicircular Hair cells imbedded in cupula inertia generates GP 9 9 AP When hard rotation stops 2530 seconds to reequilibrate Linear Acceleration Hair cells imbedded in gel with otoliths Acceleration pulls on hair cells Gravity constant 9 tonic signal know position of head Utirucle Saccule Detect linear acceleration U horizontal motion S vertical motion Mismatch of signals9 motion sickness excess rides or loss space ight L16 Efferent Nervous Systems Sympathetic Structure part of Autonomic nervous system Sympathetic chain ganglia parallel spinal cord Input from cord medulla hypothalamus No direct cortical control Preganglionic Neurons Short neurons Use Acetylcholine Ach as NT to postganglionic neurons in ganglia Postganglionic Neurons Long neurons Activated by preganglionic neurons Use Norepinephrine NE as neurotransmitter Adrenal medulla stores epinephrinenorepinephrine behaves like PostG neuron Sympathetic Responses shortlong Respond to emergencies FightorFlight Response Designed to remove danger Increase blood ow to skeletal muscle and heart Concurrent activation of motor units Decrease activity of digestive and related functions Receptor Types Adrenergic Receptors All bind NE from postganglionic neurons Determine responses from binding to norepinephrine Alpha Cause increase in tissue activity Alpha 1 9 increase 1P3 9 increase Ca release from SR 9 increase Ca Alpha 2 9 decrease CAMP 9 decrease Ca pump remove Ca 9 net increase Ca Beta 1 adrenergic receptors Increase Ca in heart open Ca channels Increase heart activity Beta 2 adrenergic receptors All over the body Increase CAMP 9 increase Ca pump 9 Ca Decrease blood vessel contraction and decrease lung bronchiole constriction more blood more air Parasympathetic Structure Part of Autonomic nervous system longshort Two neuron series all neurons use Ach as NT Cholinergic activation controls daytoday homeostatic maintenance Preganglionic Neurons Long neurons Spinal cord to organ Synapse at ganglia on organs with postganglionic neurons Postganglionic Neurons Short neurons travel from ganglia to cells Parasympathetic Responses Decrease heart rate Increase GI contractions and secretions Increase pancreatic secretions Contracts urinary bladder Relaxes internal anal and urinary sphincters AgonistsAntagonists Pharmaceuticals can mimic or antagonize autonomic NS Para increase or decrease digestive activity etc Sym increase BP in shock decrease in hypertension Motor Neurons go to skeletal muscles Alpha motor neuron gets multiple inputs up to 10000 Input from stretch receptors withdrawal re exes cerebellum learned activities cortex conscious control Both IPSPs and EPSPs to alpha motor neurons threshold Neuromuscular Junction NM Moto neuron synapse with skeletal muscle fiber cell Moto end plate produced by sodium very large synapse Acetylcholine Release Presynaptic AP 9Ca entry Ach release Ach binds to receptors on muscle membrane Endplate Potential EPPlarger than EPSP Ach binds receptor 9 increase Na entry threshold 1 motor neuron AP leads to 1 muscle AP Control of motor neuron APs control muscle activation Acetylcholinesterase AchE AchE degrades Ach to choline and acetic acid Reuptake of choline diffusion away of acetic acid NM Poisons Inhibit diaphragm can t breathe Black widow spider venom releases all Ach Botulinum Toxin blocks Ach release Botox Curare blocks Ach receptors paralyzes L17 Muscle Structure and EC Coupling Striated Muscle Structure Skeletal connects to 2 tendons tendons attach to bone Cardiac smaller cells attached endtoend stacked cans gap junctions desmosomes Muscle fibers Cell fiber Runs length of muscle in skeletal muscle Changes size thickness but no mitosis Striations deck of cards Lines in skeletal and cardiac muscle Due to filaments lined up in register Filaments overlap overlap increase during muscle contraction Dark and Light Bands Dark bands contain thick filaments may also have thin filaments Light bands have NO thick filaments only thin filaments Sarcomere Unit of contraction Z line to Z line Thin filaments are anchored to Z lines Thick filaments connect to thin filaments during contraction What one sarcomere does all do Thin Filaments polymer backbone double stranded helix twist of 2 strands of pearls Tropomyosin long thin protein polymer runs along actin Troponin binds to tropomyosin Thick Filaments polymer of filamentous protein Extension of myosin is crossbridge Crossbridge head ATP spent can bind to actin and generate force TTubulesSarcoplasmic Reticulum TT s are invaginations of muscle membranes carry APs into muscle fiber interior SR develops from ER stores Ca Connected to TT b AP down TT rotein Excitation Contraction Coupling Electrical events leading to muscle contraction Skeletal Action Potential Starts at NM synapse NT Ach binds to receptor opens Na channels and starts AP spread in both directions Release of Calcium At ttubule AP travels inward alters protein in ttubule leading to opening Ca channels in SR near TT Ca released Ca pumps at far end of SR resequesters Ca and causes relaxation TroponinCalcium Binding Ca binds to tropoinin on thin filament Tropomyosin Shift Ca bound Troponin causes tropomyosin to shift into actin groove exposing AM binding site ActinMyosin Binding mixing bowl marble A and M connect Myosin already has ATP bound and converted to ADP Pi with ADP I still bound Force Generation ADP Pi released 9 myosin shape changes head twists leading to force development No sliding Pi release in key to force development Filament Sliding Filaments slide to decrease force on crossbridge head goes to lowest energy force 0 New ATP binds to myosin actin is released and process repeats as long as Ca is elevated Relaxation Cassation of APs stops Ca release from SR Calcium pumps return released Ca to SR Tropomyosin reblocks AM binding site Muscle relaxes L18 Skeletal Mechanics Motor Unit Motor neuron and muscle fibers it innervates Motor neuron AP activates all the fibers in a motor unit Recruitment Small MUs first then larger Allows gradation of force Maximum force requires all MSs active simultaneously Asynchronous Recruitment For submaximal forces rotate activation of MUs Maintain force cannot simultaneously optimize force and continuous activity Twitch Single muscle activation 1 neural AP9 1 muscle AP 9 1 twitch Submaximal force not enough Ca reaches all troponin for full activation Tetanus Summation of twitches many APs Enough Ca so that all myosin heads reach actin Relation muscle length at which maximum force occurs Resting skeletal muscle length is near Lo Falloff at Long Lengths Reduced overlap of thick and thin filaments Falloff at Short Lengths Thick filaments compression against Z line Lo Thin filaments overlap and interfere with each other Reduced Ca release Heavy loads can only be moved slowly Light loads are moved quickly Inverse Relation High force load 9 low velocity Low force load 9 high velocity Stretched Muscles ll jml lv39 i resting length I V l leth LengthTension Curve of a Single Muscle Fiber Fo roe Figure 1 the forcevelocity curve Velocity Stretching before activation windup uses top of L T curve Better force maintenance Also activating stretch re exes 9 re ex contraction of stretched muscle Power Curve From FV curve Power F x V At all other F x V is positive must have maximum TOTAL TENSION PASSIVE FgchsElgNR TENSION F I 390 MUSCLE LENGTH L ACTIVE TENSION L19 Muscle Metabolism and Control Muscle Energy Use Progressive use of energy resources Phosphocreatine Supports about 20 sec of full activity PCr ADP 9 ATP Cr by creatine kinase reaction ATP 9 ADP Pi by myosin ATPase PCr 9 Cr Pi net reaction Pi inhibits myosin ATPase M ADP Pi 9 M ADP Pi Glycolysis 10 Rxs L3 2 min of energy use Glucose and glycogen in muscles 9 pyruvate 9 lactate No oxygen use Oxidative Phosphorylation Krebs Cycle and electron transport system 2 hours of energy support Pyruvate 9 C02 Oxygen used Carbohydrate loading increases glycogen storage increased by up to 30 Fiber Types Variations in fiber type even within same muscle Controlled by motor neuron most muscles are mixed Also called slow oxidative High mitochondria levels slow myosin ATPase slow speed High energy capacity low energy use no fatigue Also called fast glycolytic Few mitochondria fast myosin ATPase fast speed Low energy capacity high energy use easily fatigued Hypertrophy Larger cells not hyperplasia more cells High intensity high force exercise needed for maximum effect Filament Number 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 more filaments bigger cells Young 48 hour cycle 24 disassembly 24 assembly Elderly 72 hour cycle Testosterone Dependence Filament production optimized by testosterone Females with normal hormones cannot maximize muscle size Atrophy Reduction in size of muscle fibers NOT loss of number of fibers Disuse Muscle immobilized loss of filaments Easily reversible Denervation Motor neuron damage fiber loses filament Not reversible loss of myotrophic factor from neuron Electrical stimulation cannot prevent atrophy Stretch Re ex Muscle length information Monosynaptic re ex knee jerk Activation of afferent neuron produces re ex response No control by upper NCS Muscle Spindles Stretch receptors in muscles Groups of intrafusal fibers in connective tissue capsule Intrafusal Fibers Each fiber contains muscle section and stretch receptor section Fibers activate afferent neurons from receptor section of fiber Fibers also receive efferent gamma motor Nuclear bag fibers Have larger central portion of receptor Dynamic Response Only change in position Detects Highest response when muscle rapidly stretched Decreased response as stretch is sustained Rapid adaptation Nuclear chain fibers Smaller set of receptors parallel to n bag fibers Static Response osition Detects fiber Response proportional to position slow adaptation Gamma motor fibers Efferents to intrafusal fibers Contract muscle portions of intrafusal fibers Coactivation Dual activation of alpha and gamma motor neurons Alpha motor neurons contracts the muscle fibers Gamma motor neurons contract intrafusal fibers Keeps muscle spindles taut Reciprocal innervation Inhibition of paired muscle when stretch re ex occurs Afferent n 9 interneuron 9 IPSP to paired alpha motor neuron extra time Golgi Tendon Organ Muscle detectors Receptors in tendon afferent input proportional to muscle force At very high forces GTO sends IPSPs to alpha motor neurons Protective effect L20 Smooth Muscle Smooth Muscle Structure Small cells linked by desmosomes No striations Filaments parallel but not evened out spaghetti Filaments Thin filaments actin and tropomyosin no troponin TM in groove no Actin and Myosin blocking Anchored to cell membrane also in interior Thin filaments attach here and pull ends of cell Tone Force contraction with no stimulus Ca leaks in and partially activates smooth Important in BP maintenance holding cavity contents Smooth Muscle Contraction Different control mechanism than striated muscle Ca also activates Calcium Sources Most through channels across cell membrane Myosin Light Chain Kinase MLCK Ca activated Adds phosphate to myosin light chains Activate myosin ATPase for shortening and force Force Generation Myosin ADP Pi with MLCP binds actin ADP and Pi leave Myosin twists generates force Filaments slide to reduce force This part similar to striated muscle Myosin Light Chain Phosphatase MLCPase from myosin light chains Turns off myosin and causes relaxation when Ca is low Latch Removal of Pi from light chain when AM attached decreases M detachment rate Maintains force with little energy use Allows BP maintenance with low energy use allows upright position Doesn t use a lot of ATP Smooth Muscle Types Vary with function emptying cavities or maintaining force Visceral Single Unit SM One contracts all contract Use APs linked by gap junctions Phasic activity stomach Random contractions small intestine Must shorten to empty cavity Neural Effects Parasympathetic release Ach cause contraction Sympathetic release NE cause relaxation Multi Unit SM Each cell individually active no APs or gap junctions Get average force large blood vessels eye muscles Tone Very important Small force with latch low energy cost to maintain BP Force can go up or down from tone level Neural Effects Sympathetic receptor dependent Alpha open Ca channels increase contraction heart Beta 2 increase Ca pump activity decrease contraction blood vessels to heart skeletal muscles L21 Cardiac Structure and Activation Tissue capillaries Venules l Arterioles Vein LUNGS LUNGS Pulmonary vein Vein Artery Venules I Arterioles Tissue capillaries Q URGO 39AEDIC ht Arterial circulation Venous circulation Cardiac Cell Structure Cylindrical shaped cells Intercalated disks join cells endtoend Filaments as in skeletal muscle Thin filament activation by Ca binding to Troponin Intercalated Disks Strong connections between cells Desmomes for strength Gap junctions for electrical activation spread Circulatory Flow Circuit Sys LV to aorta to body to vena cava to RA Pul RV to pulmonary artery to lungs to pulmonary vein to LA Valves maintain direction of ow Cardiac Activation Structures Activation pathway has autorhythmic cells Atria Site of normal heartbeat initiation SA Node normal pacemaker drives contractions In right atrium Depolarizes to threshold starts AP Fastest depolarizer no stable baseline membrane potential The intermodal pathway connects the SA Node to the AV Node Premature beats occur if the heartbeat starts elsewhere not usually harmful Atrial Muscle Right atrium activated by SA node spreads toward the LA using the interatial pathway Spread through gap junctions Not autorhythmic contraction spreads AV Node Electrical connection from atria to ventricles AP spread allows ventricular filling to be completed AV block produces separate atrial and ventricular Ventricles AP enters septum first spreads to apex then up to ventricular muscle V muscle contraction spreads upward Bundle of His Off of AV node down the septum synapses with Purkinje Fibers Purkinje Fibers Branch off of septum to ventricular muscle Activated by bundle of His though gap junctions Ventricular Muscle Apex cells activated first by Pukinje fiber then muscle cell to cell through gap junctions Contraction spreads upward forcing blood into aorta and pulmonary artery No pacemaker activity Pacemaker Calls Autorhythmic no stable baseline potential SA and AV nodes some cells of B of H 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 neurons increases depolarization NE opens Ca channels in atria and ventricles Increases heart rate and strength of contraction Parasympathetic neurons vagus n Ach decreases depolarization rate Ach decreases Ca channel opening in atria Decreases heart rate Electrocardiogram diagram Sum of changes in cardiac APs Relation to Cardiac AP Detect changes in the sum of APs Changes in membrane potential detected by different distances to leads Ventricular Fibrillation Life threatening no coordinated emptying blood delivery Need electrical shock to recoordinate APs P Wave Atrial depolarization Start of atrial contraction 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 Left atrium Right atrtunt L22 Cardiac Pumping Aortic valve Pulnmnarv quotllVC Mttral v alvc 39l riws id valvc t p lclt vcntrtclc Blood flow through hcart Right ventricle Cardiac Cycle Sequence of contraction and relaxation 4 valves 2 AV Aortic pulmonary keep blood ow oneway Diastole Relaxed heart Time for filling End diastolic volume 130 ml Atrial Systole Contracts first Completes filling of ventricles Ventricular Systole Follows atrial contraction Contraction spreads upward Pressure must be greater than aorta to open aortic valve Aortic Pressure Load left ventricle works against High BP puts greater load on heart Ejected Blood Volume 7090 ml of blood ejectedbeat 65 of end diastolic volume Lower HR means higher ejected volume Heart Rate Dependence The maximum heart rate is 220 age Rates above 180 decrease filling time Must be motivated to exceed 180 This can decrease cardiac output Potentially life threatening Arterial Pulse Arterial walls expand to hold blood Rebounds during diastole creates pulse Little drop in BP throughout arteries Heart Sounds Closing of valves turbulent blood ow creates sounds Low pressure AV mitral and tricuspid first then high pressure aortic and pulmonary valves Different sound intensities Murmurs Nonlaminar nonsmooth ow 9 sound when valves should be closed Laminar ow does not create any sound Turbulent ow can be heard Valve Stenosis Stiff valve small opening Turbulent ow as blood squirts through Valve Insufficiency Valve leaves don t properly mesh Children with improper valve closure sometime outgrow this murmur as growth alters valve alignment Cardiac Output Amount ofblood pumpedmin Stroke Volume x Heart Rate C0 70 ml at 70 beatsmin5Lmin Body has about 5 L of blood Circulation time 1 minute Starling s Law control Increase venous return stretches cardiac muscle 9 increases force 9 CA More actinmyosin interaction less thickZ line contact less thinthin overlap more Ca release Stronger contraction more SV more CO Neural In uences Both SV and HR changes Parasympathetic Dominant at rest Cut vagus nerve to heart HR increases from 70 to 100 immed Exercise increases parasympathetic output decrease resting HR may go to 30 s or 40 s Sympathetic Increased Ca channel opening Faster depolarization causes increased HR More Ca causes more force causes increased SV L23 Arteries Arterioles Blood Vessels 3 layers in to out endothelium vascular smooth muscle connective tissue Capillaries only have endothelium Types of Blood Vessels Arteries arterioles capillaries veins Each has a different function Lymph vessels carry excess filtered uid Physical Factors Some factors constant such as vessel length Some factors variable Flow Pressure Resistance Vessel Radius Most important variable factor Resistance 1 radiusquot4 Small constriction causes large increase in resistance decrease ow Small dilation causes large decrease in resistance increase ow Short blockages can compensate with increased velocity until greater than 80 closed Viscosity Thickness of blood Controlled by hematocrit RBSs in blood 45 males 42 females need large change to in uence blood ow Above about 48 RBS interaction with arteriole walls greatly increases resistance Arterial Conductance High pressure blood enters aorta at 93 mmHg Large arteries expand to hold blood little change in BP 24 mm wide Momentum of moving blood carries blood Arterial Pressure Systolic P is 120 mmHg Distolic P is 80 mmHg Pulse pressure is Sys Dias 120 80 40 mmHg Mean arterial pressure Dia 13 PP 80 13 93 mmHg Coronary Circulation Heart Rate Dependent Decrease diastole at high HR decrease filling time and decrease coronary ow Coronary ow only occurs during diastole HR gt 180 decreases cardiac output potential heart failure Atherosclerosis Multiple stages 1 LDL lowdensity lipoprotein lays down fatty streak II WBCs and fibroblasts overgrow fatty streak III calcium infiltration hardens overgrowth hardening of the Arteries Alcohol Effect Modest alcohol consumption can solubilize fatty streak Can reverse atherosclerosis stage I Biophysical effect not receptor effect No alcohol effect on other stages Arteriolar Flow Arterioles branch off arteries 30 microns wide 93 mm Hg at artery end Carries blood to capillaries 37 mmHg at capillary end Arteriole radius can go in either direction Tone Partial activation with no stimulus Can relax vasodilate or contract vasoconstrict vasovessel dilatecontract relax Perfusion Control Sympathetic neurons metabolites Paracrines control arteriole smooth muscle NE adenosine Nitric Oxide L24 Capillaries Lymph Vein Capillary Blood Flow Very slow many capillaries spread ow out and decrease speed Capillary Pressure 37 mmHg at arteriolar end down to 17 mmHg at venous end Capillary Fluid Exchange Balance of BP forcing uid out and osmotic pressure from plasma proteins drawing uid in Fluid moves through capillary pores Filtration Dominatates at highpressure end arteriolar BPgt osmotic pressure uid forced out Reabsorption At venous end lower BP BPlt osmotic pressure uid reenters Net uid sweeps volume around capillary Slightly more uid filtered than reabsorbed Lymph Flow Return of excess filtered uid to circulation Return of Filtered uid Fluid enters closedended lymph vessels which merge with others Lymph nodes are sites of large lymph vessel merger Large lymph vessels have valves Lymph enters vena cava BP O at thoracic duct in chest Edema Swelling Excess filtration broken capillaries Low blood protein starvation alcoholism Bacteria presence and destruction draws uid osmotically Parasites filariasis block lymph ow fatal Venous Flow Capacitance vessels Hold largest blood volume Venous Pressure 17 mmHg at capillary end to O at vena cava During inspiration vessels in thorax may have negative pressure BP needs help getting blood up to heart Venous Valves Prevent back ow Every 12 inches in large veins Valves can be demonstrated on veins on back of hand Skeletal Pump Muscle contraction squeezes veins forces blood to heart Varicose Veins Ruptured valves column of blood slow return Clots may form Blood bypasses varicosities through other veins L25 Red Blood Cells Platelets Plasma Liquid portion of blood Water electrolytes metabolites hormones proteins Plasma Proteins Albumin highest amount draws uid into capillary binds hydrophobic hormones Globulins many subgroups gamma globulins are antibodies Fibrinogen final protein for blood clot formation Erythrocytes RBCs Carry oxygen and C02 No organelles only hemoglobin Hb Production In bone marrow from stem cells 20 ml of RBCday 50 ml of bloodday Low blood oxygen causes release of EPO Erythropoietin from kidneys Shape Biconcave disks 8 microns across Spectrin net under membrane helps maintain shape Fluidity of membrane allow squeeze through capillary Membranemembrane squeeze increases gas transport Destruction RBC live for 120 days Gradually lose cholesterol f cell membrane Most commonly ruptured in Spleen Adult Hemoglobin 2 alpha and 2 beta chains Each subunit has a protein globin with a heme group in the center Each hema has an iron atom at its center Oxygen binds to the iron atom Cooperatively increase binding at lungs and release at tissues Fetal Hemoglobin 2 alpha and 2 gamma chains Higher affinity binds better for oxygen than adult hemoglobin Draws oxygen form maternal blood Replaces by 23 months post natal Anemias Lack of oxygen altitude Reduced RBCs bleeding no anemia with menses 50 mlS days Reduced delivery circulatory Reduced use cyanide Sickle Cell Single Hb mutation Low oxygen 9 Hb forms stacks changes cell shape Sickled cells hand up on branch points Survival value protection from malaria parasites lay eggs in RBCs Growing malarial parasites rupture weakened RBC membranes before maturity Iron Deficiency Lack of iron decreases amount of Hb NOT from using noniron cookware wrong form of iron in cookware Platelets Pinched off parts of megakaryocytes in bone marrow Production Megakaryocytes stay in bone marrow Platelets pinch off and enter circulation Spleen kidneys and liver make thrombopoietin ThrP stimulates platelet formation ThrP binds to platelets in blood when platelets low 9 increase free ThrP Activation Activated by collagen and other proteins in connective tissue of blood vessels Platelets adhere increase ADP release more P s come and stick Make platelet plug Hemostasis Stoppage of bleeding Vasoconstriction Decreased BP at site of cut tone constricts small vessels Platelet Plug Exposure of collagen9 platelet sticking9 ADP positive feedback Prostacyclin from healthy blood vessels blocks platelet adherence Coagulation Blood clotting 2 systems Both lead to fibrinogen soluble 9 fibrin selfadhering ogen not active not in its final form Forms mesh that traps RBCs etc Intrinsic System Inside plasma collagen activated Cascade needs Ca and all factors in pathway Extrinsic System Thromboplastin from damaged tissue starts cascade Merges with IS halfway down Clot Removal Plasminogen trapped in clot 9 cascade started by collagen 9 plasmin Plasmin is an enzyme that dissolves a clot over L26 White Blood Cells Innate Natural Immunity Cell Types Leukocytes 5 types all have different defense functions Multilobed nuclei granulocytes Neutrophils eosinophils basophils Stained by neutral acid or basic dyes Singlelobed nuclei anotgranulocytes monocytes lymphocytes Phagocytes Phagocytosis of bacteria and dead cells Order of attack Resident macrophages Neutrophils new monocytes9macrophage migration Neutrophils Rapid response move from blood to damaged tissue Diapedisis squeeze through capillary pores Attack bacteria Monocytes Macrophages Monocytes move into tissue and become macrophages Resident macrophages wait for bacteria to come during infection vast movement of monocytes into infected area Massive macrophage attack on bacteria Eosinophils Produce acids that kill parasites High in GI tract Produce allergic responses Basophils Release histamine Histamine causes in ammation Increases blood ow arteriolar dilation Increases pore size allows diapedesis Defense Mechanisms Innate Nonspecific immunity Acquired Specific immunity B and T lymphocytes attack specific antigens In ammation Nonspecific response Occurs with any infection or injury Chemotaxis Chemical signals from damaged areas draw phagocytes Complement System Series of 9 plasma factors C1C9 Major bacteria killer Activation By antibodies or by the protein properdin This is opsonin tagging of surface carbohydrates on bacteria Leads to pore formation in bacteria membranes Pore Formation CCSC9 can form pores in membrane Very local rapid inactivation Pore allows osmotic lysis Na enters H20 follows cell swells and bursts Ill feeling case activation of pain receptors from partially digested protein of dead bacteria Histamine Increases blood ow brings phagocytes oxygen amino acids Increase capillary permeability opens pores for liquid and diapedesis Interferon blocks protein synthesis Cytokine Released from virusinfected cells Activate antiviral defenses in cells near virusinfected cells Many side effects Natural Killer Cells NonT cell lymphocytes No prior exposure needed for activation Activation Lipids and on bacteria tumors transplants and by antibodies on cell surface Forms pores by injecting kills by lysis L27 Adaptive Immunity B Lymphocytes Antigens Substances that activate B and T lymphocytes Most foreign some selfantigens in autoimmune diseases Antigen Presentation Proteins antigens Taken in and partially digested by macrophages Part of antigen linked to MHC protein and put into cell membrane T or B cells then find MHC protein complex 9 activate TB cell to attack on cells that have protein B Lymphocytes B cells Bind antigens full activation requires T helper contact Antigen binding triggers cell proliferation into plasma B cell clone cells and memory cells Plasma Cells Antibody factories make antibodies to antigen that bound High ER for Ab production loses other organelles Limited lifetime 1 week Memory Cells Both B and T cells A few cells have very long life Provide immunity from antigens Primary Response Activation of B or T cells is slow short and weak Secondary Response Activation of memory cells is fast strong and long Massive response upon second exposure Immunoglobulins Antibodies IgG IgA IgD IgM IgE are Yshaped proteins Variable Region Arm tips of the Yshaped protein Can bind 2 antigens Ab must be same type of antigen Constant Region Tail region Activates some aspect of immune system when antigen bound Antibody Functions Major Functions Activate the complement system to kill bacteria Labels cells for ingestion by phagocytes Activate natural killer cells Minor physiological function neutralization by binding Used for laboratory testing Blood Types Based on surface carbohydrates Genes code for enzymes that add carbohydrates Transfusion reaction if mismatch ABO System A factor B factor AB has both factors 0 has neither A or B antigen Rh Factor 2 gene system gene for factor activator gene No activator weak reaction formerly missed Rhogam given to Rh mother of Rh children Prevents formation memory cells L28 Adaptive Immunity T Lymphocytes Self T Lymphocytes Attack cells with both a and selfantigen MHC Cancer Virusinfected cells Transplants attacked Cytotoxic T Cells Bind to cell and inject perforin form pore Osmotic lysis follows Helper T Cells Release cytokines that activate all B and T lymphocytes AIDS HIV attack on helper T cells decreased immune response Opportunistic diseases can now attack Avoid multiple concurrent infections HIV needs broken skin to enter hard to get Helper T Cell Cytokines Paracrines that regulate immune response Increase proliferation growth and function When cytokine structure known renamed an interleukin Major Histocompatibility Complex Previously known as HLA antigens MHC Class I self antigens on surface of all cells Identify cells as self 36 out of 100 possible antigens on every cell Others in foreign cells attacked MHC Class II ingest and present antigens activate T cells Transplants Nonmatching MHC I cells are attacked by antibodies Partial match has both self and foreign antigen triggering T lymphocyte attack Try to match MHC Class I proteins T cells may attack suppress T cells more infections Leukemia replace marrow fungus risk Tumors Benign tumors stay localized no infiltration of surrounding tissues Malignant tumors have transformed cells cancer Can infiltrate nearby tissues Can metastasize to other parts of the body Allergies Immune reaction to a harmless substance Allergens can produce responses Immediate Hypersensitivity Immune response in 20 minutes B cell mediated antibody production Stimuli Nonbacterial pollen bee stings penicillin mold dust IgE antibodies Many in skin eyes lungs GI tract System designed to attack parasitic worms Chemical Triggers Histamine vasodilatation and capillary permeability increase SRSA strong bronchiole contraction potentially lethal Symptoms Localized reaction Upper respiratory hay fever congestion edema sneezing runny nose Bronchioles asthma in ammation constriction Anaphylactic Shock Allergens spread by blood Severe hypotension due to increased capillary permeability Bronchoconstriction Treat with epinephrine Delayed Hypersensitivity Immune response in 24 hours T cell mediated Poison Ivy some toxins stimulate T cells migrate to area of contact and produce rash Skin Mechanical barrier with defense mechanisms Different layers Epidermis Layers of epithelial cells Dead cells outermost with dividing cells beneath No blood supply supplied by diffusion from the dermis Desmosomes and keratin fibers hold cells together with keratinized layer remaining after death Pathogentight airtight fairly water tight prevents evaporation Burns destroy epidermis cause hypotension and shock Dermis Connective tissue beneath the epidermis Blood vessels nerve endings many cell types Blood regulates heat loss Sweat glands sweat has variable Na content Sebaceous glands oil waterproofs skin Hair follicles increase touch sensitivity Melanin absorbs UV light UV sensitive Langerhans cells present antigens UV resistant Granstein cells slow immune responses Net UV light increases skin cancer Hypodermis Adipose tissue insulates body from heat loss L29 Lung Structure Breathing External Respiration Exchange of gases 02 and C02 between body and environment Internal respiration use of 02 by mitochondria NonRespiratory Lung Functions Water and heat loss increases venous return acidbase balance speech pathogen defense circulatory modification ACE sense of smell Lung Structure Trachea 9 bronchi 9 bronchioles 9 alveoli 20 generations of bronchioles Alveoli are air sacs sites of gas exchange Type I Cells Epithelial cells 1 micron thick Separate air from interstitial uid Type II Cells In alveoli Produce surfactant decrease to alveolar opening Lung Mechanic Air ows from high pressure to low pressure Atmospheric Intraalveolar Intrapleural Pressures A 760 at sea level 600 at Denver 1 mile up IA variable exhale 12gt atm inhale 12 lt atm IP between lungs and thoracic wall Always 4 mmHgltatm Lower pressure keeps lung always in ated Boyle s Law Ppressure x Vvolume constant Decrease V 9 increase P Increase V 9 decrease P Inspiration taking air into lungs Regular phrenic nerve from medulla sends AP to diaphragm Diaphragm contraction increas es thorax volume Decreased pressure causes inspiration Expiration air out of lungs Normally passive As diaphragm relaxes volume decreases pressure increases expiration Extra Expiration Internal intercostal muscles between ribs contract Abdominal muscles contract also Squeeze thorax Compliance Ease of lung expansion Normally easy Increases fibrosis asbestosis of lungs decrease compliance Alveolar Surface Tension Adherence of H20 molecules creates surface tension on inside of alveoli Surface tension must be overcome to open alveoli Surfactant Several phospholipids mix with water and decrease surface tension Also prevents edema in lungs First made at 36th week of gestation Glucocorticoids increase surfactant production in premature infants Anatomical Dead Space Normal tidal volume is 500 ml 150 ml of mouth pharynx trachea bronchi bronchioles is dead space 350 ml is normal alveolar in ation Long slow breather minimizes dead space effect Short rapid breathing still must fill 150 ml dead space L30 Gas Exchange Partial Pressures Gas equivalent to cation Sea level 760 mmHg 600 N2 160 02 C02 03 mmHg Gases independent of one another Air in lungs is water saturated Alveolar Air Alveoli 02 P02 100 mmHg PC02 40 Capillaries C02 Venous blood P02 40 PC02 46 C02 from tissues to atmosphere high to low 02 from atmosphere to tissues low to high Diffusion Across Alveolar Wall Gases follow partial pressure gradients Capillary gases match tissue it goes through 02 02 enters pulmonary capillaries until P02 is 100 C02 C02 leaves pulmonary capillaries until PC02 is 40 Pulmonary Circulation Lower BP than aortattg 1520 mmHg MAP of pulmonary artery Ventilation Perfusion Ratio Ventilation and perfusion normally well matched 08 Areas that have open alveoli get more blood ow As need for gas exchange increase both blood ow and ventilation increase in new lung areas Tissue Gas Exchange Reverse of lungs 02 100 mmHg arterial blood loses 02 to 40 mmHg tissue until capillary is 40 mmHg C02 40 mmHg arterial blood receives C02 from 46 mmHg tissue until capillary is 46 mmHg Oxygen Transport 15 carried by dissolved 02 985 carried by binding to hemoglobin OxygenHemoglobin Binding Sigmoidal curve cooperatively between 4 Hb subunits 1m 2 75 a 2 t 2 i 2 a 50 2 3 s z 5 5 n 25 2 5 0 A 100 p02 mm Hg Plateau Region Steep Region P at lungs all Hb is 02 bound no effect of extra 02 S at tissues fall in P02 unloads 02 At lower P02 even more 02 delivery work hard get oxygenquot Bohr Effect C02 acid shift Hb02 curve to the right More 02 unloading at given P02 Carbon Monoxide 2 effects Binds Hb 200x stronger than 02 less 02 available Never dissociates must lyse RBC to lose C0 Shifts Hb 02 curve to left less 02 delivery Hypoxia Low blood 02 Low 02 air high altitude or 02 deprivation High altitude ethnic groups higher Hb even at sea level Sea level ethnic groups low 02 training increases HB lose when return to sea level Hyperoxia Breathe high 02 air no additional Hb binding already full Increase dissolved 02 may decrease breathing rate benefit only Psychological Carbon Dioxide Transport 10 dissolved 30 bound to plasma protein and Hb 60 converted to bicarbonate by carbonic anhydrase CA Carbonic Anhydrase In RBCs Hypocapnia Low C02 Hyperventilation decreases C02 in blood 9 faint Breathing into bag increases C02 back to normal Hypercapnia High C02 increase breathing rate Increase C02 in blood strongest stimulus for increased respiration L 31 Regulation of Respiration Lung Diseases Medullary Control Centers Dorsal Respiratory Group DRG rhythmic discharge 9 phrenic nerve 9 diaphragm Initiates normal breathing Ventral Respiratory Group VRG causes increase inspiration expiration Pontine Control Centers Modify medullary centers Pneumotaxic Center switches off inspiration Apneustic Center prolongs inspiration normally inhibited If PC damaged Hering Bruer re ex from lungs stops inspiration Chemical Control of Respiration Most powerful controller of rate Increase blood C02 9 increase brain C02 9 increase H and HCO3 H in brain increases DRG rate Peripheral Changed In carotid bodies and aortic bodies Increase H or increase C02 or decrease 02 will increase rate of inspiration Little effect in normal range P02 lt 60 mmHg increase rate no help in CO poisoning Sleep Apnea Decreased DRG activity or airway obstruction In REM pharyngeal muscles relax and tongue trachea Decreases restful sleep SIDS Sudden Infant Death Syndrome Exact cause unknown May be due to congenital DRG problem or cardiac arrhythmia Baby sleeping on back decrease SIDS mother smoking in pregnancy increases SIDS Child abuse may have skewed SIDS statistics Pneumothorax Rupturing of thorax air enters Intrapleural space Pressure equalizes lung collapses on rupture side Decreased ow in good side Danger of kinking of great veins if opening remains Reclosed normal breathing on good side lung rein ates Asthma Episodic or chronic wheezing tightness in chest Increased morbidity and mortality Airway Obstruction Increased mucus production in response blocks airway Reduces air ow In ammation Response to allergies increase IgE Increase mast cell release of histamine and other cytokines Edema decreases air ow Bronchoconstriction Some cytokines are bronchoconstrictors Constriction decreases air ow SRSA Slow Reactive Substance of Anaphylaxis leukotrienes Powerful bronchoconstrictors during allergic attacks Potentially fatal attack Epinephrine Beta 2 receptors bind Epi relax bronchioles increase air ow Rescue from serious allergic attacks Steroids decrease in ammation 9 side effects significant Emphysema Cigarette smoke coal tar most common causes Decreased aAntitrypsin Lungs have digestive enzymes for defense Alphaantitrypsin protects lung tissue from digestion Inhibit AlphaAT production and enzymes digest alveoli Decreased of alveoli and increased size of remaining alveoli Surface Area Progressive decrease in surface area May need pure 02 to fill Hb Irreversible right heart enlarges and fails Cystic Fibrosis Recessive gene decreased Cl channel activity Loss of airway Na and water mucus sticky and digestive enzymes increase Increased infection lung destruction L 32 Renal Filtration Reabsorption Renal Functions Filter waste from blood Maintain blood volume Maintain blood osmolarity Uses filtration Reabsorption secretion Nephron Functional unit of the kidney Has vascular system and tubular system All but cells and proteins in blood can be filtered Most reabsorbed remainder urine Vascular System 2 capillary systems 1 for filtering 1 for Reabsorption Afferent arteriole 9 glomerulus filtration 9 efferent arteriole 9 peritubular capillaries Reabsorption 9 venules Tubular system S Shaped Bowman s Capsule receives filtrate 9 proximal tubule 9 Loop of Henle 9 distal tubule 9 collecting duct 9 ureter Variable reabsorption Hormonal control of volume and osmolarity Glomerular Filtration From glomerulus into Bowman s Capsule Glomerular capillaries have very wide pores Only cells and proteins not filtered Inulin Fructose polymer Filtered not reabsorbed or secreted Used to measure glomuler filtration rate GFR Inject in blood measure in urine proportional to amount to filtrate GFR 125 mlmin 140 of total blood volume Hydrostatic Osmotic Pressures H BP force filtrate into Bowman s Capsule OP So much uid is filtered remaining proteins have higher than normal osmotic pressure Net lots of filtration Control of GFR Afferent arteriole radius controls entry to glomerulus Aff Art dilation increases GFR Aff Art Constriction decreases GFR Sympathetic n constricts Aff Art decrease GFR Tubular Reabsorption Must recover most filtrate 125 filtered 124 mlmin reab 9 1 mlmin urine 144Lday 125 filtered 123 mlmin reab 9 2 mlmin urine 288 Lday Excess urine loss in diabetes 9 decrease blood pressure 9 shock 9 death Transport Maximum Different carriers for different molecules Tm is limit of transport due to limited of carriers Glucosuria 3x more carrier capacity than normal filtered load If G in urine blood must have at least 3x more G than normal Sodium Reabsorption Controls reabsorption of many other molecules Na pump only on basolateral side of tubular cells Pump Na out create gradient for Na entry into cells ATP needed for energy Tight junctions prevent ow in spaces between cells Caffeine decreases Na reabsorption Cotransport Carriers for Na and cotransported molecule Glucose amino acids bicarbonate C1 are cotransported with Na during reabsorption Energy use is Na movements down gradient into cells H20 follows osmotically at proximal tubule Variable H20 reabsorption at distal tubule and collecting duct Glucose Reabsorption Binds to carrier with Na on luminal side to enter tubular cell Separate nonNa glucose carrier moves G into interstitial space Proximal Tubule Water Reabsorption 6070 of water reabsorbed in PT 180 L day filtered 1 L of urine variable 500 ml of urine minimum per day to remove toxins Osmotic reabsorption of water follows solutes especially Na L33 Renal Control Secretion Filtrate Dilution Production of Angiotensin II Renin coverts angiotensinogen into angliotensin I Angiotensin converting enzyme ACE converts Al to All ACE is in the walls of lung capillaries Effects of Ang 1 Powerful vasoconstrictor 9 increase BP Causes release of aldosterone from adrenal cortex ACE Inhibitors Block production of Ang 11 Used as treatment for hypertension Few side effects but may produce fetal development problems Tubular Secretion Extra removal from plasma Carriers and pumps move material from tubular cells into filtrate Most secretion is at proximal tubule Organic acids and bases secreted medicines dyes food additives Renal Blood Flow PAH PAH is totally secreted from plasma Appearance in urine proportional to renal blood ow H Secretion C02H20 9H2C039 H HC03 Carbonic anhydrase in tubular cells makes H and HC03 H secreted in both proximal and distal tubules Uses NaH countertransport H into filtrate HCO3 9 interstitial uid net loss of H K Secretion K reabsorbed in exchange for Na in proximal tubule The Na pump increases tubular cell K which increases its secretion by the proximal tubule cells 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 kidney s ability to remove a substance from the plasma It is the volume of plasma from which an amount of material has been removed Glucose has zero clearance If a substance is filtered but not secreted or reabsorbed like inulin its plasma clearance is the GFR If a substance is both filtered and secreted its clearance is greater than GFR If a substance like PAH is filtered and entirely secreted its plasma clearance is the renal blood ow 2025 of C0 GFRREF C inulinCPAH Filtration Fraction 20 Loop of Henle Creates osmotic gradient in kidney medulla 300 m0sm at cortex 1200 m0sm in deep medulla Filtrate at the end of the LofH is 100 m0sm Plasma is 300 m0sm Countercurrent Multiplication Descending limb of LofH is H20 permeable Ascending limb is H20 impermeable H K Cl pumped out Filtrate entering distal tubule always dilute 100 m0sm L34 Urine Production Bladder Function Collecting Duct Goes through from cortex to medulla Always dilute filtrate at cortical end Responds to vasopressin no VP 9 little water reab 9 dilute urine Vasopressin From posterior pituitary Released when plasma osmolarity high Causes insertion of aquaporins in CD membrane Aquaporins H20 channels H20 goes through AqP Osmotic pressure of solutes in medulla 91200 m0sm draws water Retain H20 urine up to 1200 mOsm Diabetes Insipidus Either decreasing VP production or lack of kidney response bad receptor Excess water loss 9 shock 9 death Need to drink much water to survive Urine Buffering Filtrate pH must be 45 or greater for H to enter filtrate Bicarbonate and Phosphate from filtration and ammonia from tubular secretion buffer urine Aldosterone Effects Increase of active Na carriers on luminal side of CD tubular cells This increases Na reabsorption in collecting duct H20 follows osmotically K reabsorption is reciprocal to Na Secondary Hypertension Reduced renal artery ow decrease renal BP 9 excess renin 9increase BP Treat with ACE inhibitors to block Ang 11 production Diagnosis by determining RBF with PAH Renal Dysfunction Wide Glomerular pores 9 protein in urine 9 edema due to low protein Loss of concentrating diluting loss of nephrons multiple causes Acidosis by eg lack of ammonia reduced H excretion 9 decrease neural function Sodium Dysfunction Excess Na Na retention leads to edema hypertension Decrease filtering excessive aldosterone lead to heart failure Bladder Function Storage of urine No changes after leaving kidney Ureter Entry Ureter connects kidney to bladder Ureter passes inside bladder wall at an angle Increased bladder pressure closes ureters prevents back ow Bladder Sphincters Around urethra the tube draining the bladder Internal urinary sphincter is smooth muscle involuntary External urinary sphincter is skeletal muscle voluntary Control of Micturition urination Spinal re ex relaxation of internal sphincter when bladder pressure increases Re ex relaxation of external sphincter follows Cortex can overcome re ex relaxation of external sphincter Parasympathetic neurons increase bladder body contraction Pelvic oor descends allowing urine ow Exercise after delivery maintains pelvic oor strength L35 Fluid Balance Balance Concept The ECF is the pool of available material for cells Input comes from ingestion or metabolic production Output occurs from excretion or consumption Balance must occur over the long run with input output Negative Balance Ouput is greater than input Net reduction in pool concentration Positive Balance Input is greater than output Net increase in pool concentration Fluid balance of H20 in the body 60 of the body is H20 with adipose tissue causing variation Plasma 90 water soft tissues 7080 bone 22 adipose 10 Intracellular 23 of total body water K dominated with protein Extracellular Fluid 1 3 of total body water Na dominated Plasma 20 of ECF with protein Interstitial Fluid 80 of ECF no protein Minor ECF Components Relatively small volumes lymph CSF saliva etc ECF Volume Regulation Regulation of volume needed for longterm BP control Changes in BP cause shifts of uid between plasma and IF Blood Pressure Control Short term a drop in pressure causes Autotransfusion Movement of uid from IF to plasma to maintain BP Changes in baroreceptor activity Longterm control of volume is balance of thirst intake and kidney uid excretion Salt intake The kidneys need 05g 500 mg NaClday for uid loss in sweat feces Intake is 105 10500 mG NaCl day excess excreted in urine Cl follows Na Salt Excretion Kidneys good at eliminating Na but inc retention inc BP Must balance 105gday input Fitness reduces Na content in sweat Long term control of Na excretion controls BP Everyone has their own set point for BP ECF Osmolarity Dissolved Stuff Control Needed to prevent swelling or shrinking of cells Total amount of material in a volume regardless of composition produces its osmolarity Ions Na and K dominate the osmolarity of ICF and IF Other nonpenetrating substances like proteins also contribute to osmolarity Water moves by osmosis if there are differences in ICF and IF osmolarity Tonicity What actually happens to a cell A relative condition comparing 2 things Water and red blood cell The standard for the tonicity is not the number of dissolved particles but the behavior of cells in the solution Cells swell in hypotonic solutions ECF is rarely hypotonic Hypertonicity Cells shrink in hypertonic solution gtthan 300 mOsm Dehydration low intake excess loss diabetes Vasopressin Controls osmolarity of urine VP adds aquaporins to collecting duct to increase water reabsorption Water Intake Fluid drinking food intake metabolism add water Balance water loss from lungs skin sweat feces urine Osmoreceptors Receptors in hypothalamus that control VP release Increased osmolarity inc VP release inc H20 Decreased osmolarity dec VP release inc H20 excretion L36 Acid Base Balance Acids Acids are AH acids dissolves into A and H Strong acids like HCl in the stomach completely dissociate Weak acids like H2CO3 carbonic acid partially dissociate Bases Bases B can bind H to become BH The only significant physiological base is ammonia NH3 becomes NH4 Ammonia buffers renal filtrate allowing more H excretion pH Measure of H in a solution pH logH increases in H cause decreases in pH The average blood pH is 740 average cell pH is about 70 Blood pH below 735 is acidosis Blood pH above 745 is alkalosis Acidosis is far more common than alkalosis Cells will have bigger pH shifts than blood Acidosis Effects Acidosis depresses the neurons especially in the CNS Alkalosis makes neurons hyperexcitable Acidosis in general decreases enzyme activity but a few increase Acidosis causes increased H excretion and therefore decreased K excretion Increased K causes cardiac and neural problems Sources of H Small amounts in food such as citric acid Most generated in the body carbonic acid from C02 sulfur and phosphoric acids from proteins metabolic acids such as lactic acid Control of H H is controlled in three ways chemical buffering respiratory control of C02 and renal control of H excretion Buffers Different buffers work in different places Buffers work by binding H converting A into AH This removes H from the solution and from pH First line of H defense Extracellular Buffering Bicarbonate is the most important ECF buffer HC03 bind H to form H2C02 which dissociates to C02 H20 Hemoglobin in RBCs buffers H produced by C02 increases in venous blood Intracellular Buffering Proteins in cells bind H in ICF In some cells especially muscle cells phosphate helps buffer ICF Urine Buffering Phosphate and Bicarbonate are dissociated acids that buffer renal filtrate Ammonia is a base that also buffers renal filtrate Respiratory Control of H Second line of H defense works with nonrespiratory sources of H Increased H of increased C02 increase depth and frequency of respiration This reduced C02 in blood reducing H back toward normal Kidney Control of H Third line of H defense Removes H from any nonrenal source in the body H Excretion H ion pumps in the renal tubules secrete H into the filtrate Urine pH is normally 60 but can be as low as 45 Acid Base Imbalances Pathological changes in the control of H result in pH changes These can be compensated by the respiratory and renal systems if not of respiratory or renal origin A system cannot compensate for its own problem renal problems require respiratory compensation respiratory problems require renal compensation Respiratory Acidosis Abnormal C02 retention from hypoventilation Lung disease drugs nerve muscle disorders breath holding Renal compensation by increased H secretion Respiratory Alkalosis Decreased C02 by hyperventilation Fear anxiety aspirin poisoning conscious breathing Decreased H secretion or removal of condition Metabolic Acidosis produced by something in body Most common acidbase disorder Severe diarrhea loss of bicarbonate Excess H production during fat use in diabetics Exercise leading to lactic acid and H production Kidney failure cannot excrete H or conserve HCO3 Metabolic Alkalosis produced by something in body Decrease in H for nonrespiratory reasons Vomiting loses H in vomitus Excess bicarbonate ingestion Decrease respiratory rate and retain H in kidneys to compensate H retention increases K loss L 37 Cardiovascular Regulation Hypertension Local Control Decrease Pressure 9 decrease ow 9 homeostatic tissue response 9 increase ow Autoregulation each organ controls local blood ow Metabolic Vasodilators Active tissues produce vasodilators ATP use 9 increase adenosine production Adenosine is a strong vasodilator active hyperemia Endothelial Factors Paracrines Released from endothelium affect VSM vascular smooth muscle Nitric Oxide N0 Hormonal neural activation Increase NO 9 relaxes VSM 9 increase blood ow Endothelin Peptide constricts VSM Decrease ow 9 increase BP Stimulants of E increase gene activity that makes E Baroreceptors Stretch receptors in carotid sinus and aortic arch Changes in BP alter baroreceptor activity Input to Medulla Baroreceptors send neurons to medulla in brain stem Control of Vasoconstriction Dilation Cardiovascular Control Center CCC is in medulla CCC controls sympathetic and parasympathetic output Homeostatic shortterm control of blood pressure Sym decrease BP 9 decrease baroreceptor input 9 increase sympathetic output 9 increase BP heart VSM Para Increase BP 9 increase baroreceptor input 9 increase parasympathetic output 9 decrease BP lower HR Resetting Body adjusts to own normal BP Adaptation to prolonged BP change occurs over days Hypertension Chronic elevated BP Multiple causes several small changes cause large increase in BP Cardiac Effects Hypertrophy against increased load diastolic pressure Increased oxygen use 9 heart attack when coronary constrict With age increases in systolic pressure increase stroke risk Essential Hypertension Cause unknown treat symptoms Effective reduces pathology Renal Hypertension Also called secondary hypertension Decrease blood ow to kidneys cause increase kidney renin release Renin converts angiotensinogen to angliotensin AI Angiotensin converting enzyme ACE in lung capillaries converts Alto Angiotensin II Angiotensin 11 increases BP Angiotensin II is a strong vasoconstrictor and causes aldosterone release from adrenal cortex Aldosterone increase Na reabsorption and H20 reabsorption by kidneys more volume In pregnancy Placental factor causes vasoconstriction Preeclampsia is hypertension during pregnancy Drug Treatments Often used in combination Varying side effects Diuretics Increases Na excretion lowers blood volume decreases BP ACE Inhibitors Block conversion of Angiotensin I to Angiotensin II aAdrenergic Receptor Blockers Drops sympathetic constriction of VSM blocks NE effects Fewer Ca channels open less Ca entry less force BAdrenergic Receptor Blockers Blocks NE Epi effects on heart less Ca entry Decreases force of cardiac contractions Calcium Channel Blockers Decreases VSM contraction blocks tone Very low blood pressure Loss of blood Toxic vasodilation Reversible Shock can recover from Epinephrine increases BP side effects significant Irreversible Shock multiple organ failure due to low BP Death results L 38 Digestion and Absorption The breaking down of food into absorbable units and their absorption Carbohydrate Digestion Must be reduced to monosaccharides to be reabsorbed Complex Carbohydrates Chains of sugars usually glucose Different complex carbs have different links between sugars Starch is different than cellulose we cannot digest cellulose Sugar in fruit is often monosaccharide fructose or glucose Enzymes Produced in the mouth and in the pancreas Amylase converts starch to disaccharides Disaccharides are in wall of the SI Disaccharidases convert disaccharides to monosaccharides Sucrose is converted to glucose and fructose Lactose Intolerance Lactose is milk sugar disac of glucose and galactose If no lactase is produced no digestion of lactose Bacteria in L1 use lactose as food source Gas and diarrhea produced Absorption Complete all sugars totally absorbed No diffusion use glucose transporters Sodium Dependence Glucose cotransported with Na into epithelial cells Transport of glucose from epithelial cells to interstitial uid uses a nonNa glucose transporter Protein Digestion Some in stomach most in small intestine Proenzymes Released in protected form Acid then pepsin converts pepsinogen into pepsin Enterokinase in SI wall converts trypsinogen into trypsin Trypsin then converts other pancreatic proteases into active form Peptidases Both from pancreas and on SI wall Convert peptides into amino acids Some di and tri peptides absorbed Absorption Use amino acid transporters in mucosal wall Some use Na C1 or no cotransporter Sources of Protein 50 food 25 digestive enzymes 25 mucosal cells No dietary protein in feces Infant Protein Absorption Newborns can absorb protein directly until tight junctions form IgG in colostrum provides protection Lipid Digestion Mouth and stomach lipases unimportant Pancreatic lipases enter duodenum in active form Lipases Convert lipids to absorbable form Lipases convert triglycerides into monoglycerides and free radicals Micelles Bile salts from liver emulsify MG and FFA and cholesterol Fats diffuse into mucosa at brush border Absorption Monoglycerides MG and Free Fatty Acids FFA cross and reform into TC in mucosal cells TG and Cholesterol from chylomicrons Chylomicrons enter lymph thru thoracic duct to liver Portal Vein Carries water soluble foods directly to liver Liver processes and detoxifies foods Fats9 Lymph 9 blood 9 everywhere 9 liver eventually Electrolyte absorption Salts all H20 soluble 9 portal vein SI has tight junctions Water 2000 ml day ingestion 7000 ml day secretions 200 ml day in stool Follows other absorption osmotically Sodium Most Na enters through cells energy gradient from Na Pumps on basolateral side of mucosa as in kidney Potassium K enters down concentration gradient through channels K exchanges for Na last electrolyte absorbed Bicarbonate Huge secretion by pancreas buffers acids in duodenum Reabsorbed by concentration gradient in SI Vitamins Water soluble B and C Vitamins rapidly absorbed rapid loss in urine Must take in B and C Vitamins daily 312 absorption needs intrinsic factor from stomach Vitamins A D E K fatsoluble 9 micelles 9 9 lymph Minerals Ca2 3080 absorbed Vitamin D dependent Ca2 binding proteins and Ca2 ATPases increase Ca2 entry L 39 GI Intro Mouth Esophagus GI Layers Mucosa epithelial cells inner Submucosa longitudinal muscle submucosal plexus right below it Muscularis circular and longitudinal muscle myentric plexus Serosa outer epithelial layer produces serosal uid GI Innervation Plexuses neurons control local contractions Longitudinal muscle propulsion of chyme Circular muscle mixing food and secretions Parasympathetic Neurons Activate plexuses 9 increase GI activity Sympathetic neurons 9 decrease GI activity Basic Electrical Rhythm Variable electrical baselines Ca2 and K channels open close Contraction when BER reaches threshold and APs occur Migrating Motility Complex Strong contraction migrates from stomach to end of SI Starts as previous meal nears complete digestion Clears stomach and S1 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 of acid and pepsinogen Increase SI ileocecal valve relaxation 9 empties SI Initiates mass movement in L1 that triggers defecation Cholecystokinin CCK Secreted by duodenum into blood Causes contraction of the gall bladder Causes release of pancreatic digestive enzymes Inhibits stomach secretions Secretin Secreted from duodenum into blood Increase secretion of pancreatic bicarbonate into pancreatic duct Bicarb neutralizes stomach acid in duodenum Mouth Little digestion here Almost no absorption only some medicine Nitroglycerin absorbed by oral mucosa Secretions Bicarbonate neutralizes acids H20 amylase lipase mucus to coat food Lysozyme antibacterial enzyme Swallowing Deglutition Boluses formed coated with mucus Voluntary propulsion to pharynx Re ex relaxation of upper esophageal sphincter Bolus forced into esophagus Esophagus Tube to stomach sphincter at each end 59 seconds transit time to stomach No digestion or absorption Sphincters Upper e sphincter relaxes upon swallowing Peristaltic contractions behind bolus force it into stomach Lower e sphincter normally tightly closed relaxes to let bolus in Re ux Acid into esophagus through LES Loss of neural input most common cause Acid irritates esophagus heartburn potential ulcer Gas In stomach Swallowed gas some burped out some absorbed some to colon Most colonic gas is bacterial L 40 Stomach Pancreas Liver Stomach Holds contents kills pathogens starts protein digestion Relaxes as food enters holds up to 1 liter Structure Lining has gastric pits cells produce secretions Mucus coats gastric pits prevents HCl killing cells Secretions Pepsinogen HCl separate H and Cl pumps pH 12 Mucus Gastrin intrinsic factor for 312 absorption Motility Peristaltic waves 3 min fundus to body to antrum Forces food into antrum crushes boluses there forms chyme Chyme is 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 Open sores in stomach cells exposed to acid Kills cells no mucus covering Histamine Acid 9 damage 9 histamine 9 more acid Positive feedback loop Treatments stop acid secretion neutralize acid H Pylori Bacteria Live in gastric pits 50 of all ulcers Exocrine Pancreas Secretes bicarbonate solution to neutralize stomach acid Secretes enzymes for digestion Duct System Carries solutions to duodenum 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 liters day Regulation Increased H lower pH in duodenum causes secretin release into the blood Secretin from duodenum causes release of Na Bicarb solution PASS Enzymatic Secretions Proteases released in protected form Lipase and amylase released in active form Pancreas has trypsin inhibitor for protection Liver Regulation Fat or protein in the duodenum causes CCK release CCK causes acinar cells to release enzymes Enzymes carried to duodenum by PAAS Parasym neutrons increase enzyme release sightsmell response Released bile into duodenum to emulsify fats Mostly undifferentiated cells 1000 s of metabolic reactions Makes plasma proteins Blood Supply 2 sources merge at liver sinusoids Hepatic artery supplies oxygenated blood from heart Portal vein carries watersoluble foods from SI Bile Salts Major component of bile made by hematocytes Released into bile canaliculi on opposite side from blood Bile salts form micelles 9095 of bile salts reabsorbed at ileum recycled Bilirubin Metabolism Formed from heme of lysed RBC s fatsoluble circulate bound to albumin Released to liver cells 9 modified to H20 soluble form 9 most to bile 9 feces Some is reabsorbed at the ileum excreted in urine Provides color for both urine and feces Iaundice is a buildup of bilirubin usually liver problem Gall Bladder Function Stores bile between meals when Sphincters or Oddi closed 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 with glycoprotein binding Can block S of O gall bladder attack If GB removed bile duct expands to hold bile L41 Small Intestine Large Intestine Small Intestine Primary site of digestion and absorption Structure Duodenum jejunum ileum Many folds increase surface area 600 fold 9 lday presented 2 food 7 secretions 12 lday to colon 200 ml in feces Villi Folds of the SI wall tissue Crypts of Lieberkuhn at base Cells migrate upward die by digestion Cells replaced every 3 days Microvilli Brush Border Folds of cell membrane at the tips of villi cells Side of absorption Bound enzymes on surface Enterokinase disaccharides Mucus Secreted with 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 of longitudinal smooth muscle Segmentation mixing contractions of circular smooth muscle Malabsorption Decrease amino acid absorbance 9 wasting decrease muscle mass Decrease carb and fat absorbance 9 increase stool and gas decrease vitamin absorbance Autoimmune Crohn s and allergic gluten enteropathy diseases Diarrhea Multiple causes most common SI motility 9 absorption Loss of H20 and K potentially serious or fatal neuralheart problem Dehydration leads to shock Travel change in water electrolytes kills LI bacteria or E Coli other bacteria in food Large Intestine Colon Handles absorption of H20 and Na and some K No nutrient absorption except some from bacteria Structure SI 9 cecum 9 ascending transverse descending colons 9 rectum 9 anus Internal and external sphincters control anus Appendix closed pouch of lymphoid tissue off cecum Gastroileal re ex Food in stomach causes relaxation of cecum and allows ileum to empty Gastrin relaxes ileocecal valve Absorption 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 may decrease colon cancer Bacteria E Coli and other types appear soon after birth May produce useful vitamins and essential amino acids Can invade body after radiation poisoning Defecation Gastrin triggers colonic contraction 9 mass movement into rectum increases pressure Increase rectal pressure causes re ex relaxation of internal anal sphincter smooth muscle Voluntary control of external anal sphincter skeletal muscle Constipation Defecation varies from 3 days to 13 days No significant health consequences except discomfort No poison absorption Flatus Most is bacterial some from ingestion Multiple gases smell is due to sulfides Sound gas forces through closed sphincter Basal Flatal Rate 15 mlhour 1 passagehour Postprandial Flatal Rate 176 mlhour after one helping of baked beans increased frequency L42 Energy Balance Energy Input Energy in ingested food Digested food energy trapped in ATP phosphate bonds ATP used to drive physiological functions Energy Output External work used to move objects or the body Internal work posture shivering internal activities needed for life synthesis etc All activities ultimately become heat Basal Metabolic Rate BMR Energy Time CaloriesDay 2000 Calories day are 2000 kilocalories day Neutral Balance Energy input energy output Food energy external work internal work heat Positive Balance Energy input gt energy output Energy stored in adipose tissue weight gain Negative Balance Energy input lt energy output Weight lost first from adipose tissue then from muscle Hypothalamic Control of Intake Hypothalamus integrates multiple signals matching feeding to energy needs Balance of hunger and satiety Neuropeptide Y Released by HT stimulates appetite Melanocortins Released by HT suppress appetite NPY and MCs alter brain activities that control food intake Leptins Secreted by adipose tissue proportional to TG storage in adipose Increasing fat stores signals satiety by releasing leptins Leptins decrease NPY and increase MCs Digestive System Appetite Control Hormones from the GI tract control hypothalamic release GhrelinPYY3 36 Ghrelin rises before eating stimulates appetite and falls after eating Increases NPY release PYY released during meals and signals satiety CCK The release of CCK signals satiety before digestion has occurred stop eating before the new calories available 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 Caloric intake often strongly in uenced by outside factors Obesity decreased exercise BMR biochemistry differences habit hormonal differences etc increase morbidity and mortality Anorexia nervosa psychological start K imbalance Temperature Regulation 987 F 37 C Convulsions at 106 Death from protein denaturation at 110 Core temperature is regulated shell variable Heat Balance Balance of input and output Internal heat must be removed Multiple heat exchange mechanisms Heat Exchange Radiation by electromagnetic waves sun fireplace Conduction transfer by contact from warm to cold Convection airwater currents increase transfer Evaporation of water from skin removes heat Sweat increases evaporation dripping doesn t Fitness decreases sweat salt content inc evaporation Heat Production Muscle Contraction Shivering is contraction without work all heat BMR sets lower limit of heat production Response to Cold Hypothalamus thermoreceptors control responses Decreased skin blood ow goosebumps ineffective Human adaptation movement clothing outside sources Response to Heat Increased skin blood ow increased sweating adaptation Fever WBCs release endogenous pyrogen reset hypothalamus Aspirin blocks prostaglandin production L43 Principles of Endocrinology Circadian Rhythms Calcium Control Hormones Released from endocrine glands into the blood go everywhere Bind to receptors effects on different cells receptor dependent Hydophilic hormones bind to membrane receptors Hydrophobic hormones bind to nuclear receptors alter protein synthesis Plasma Hormone Concentrations Controlled by feedback mechanisms Hydrophilic hormones can change concentration rapidly mins Hydrophobic hormones often partition into adipose tissue This buffers changes in plasma concentration hours Negative Feedback Concentrations vary minimally around a set point Falling concentrations stimulate release mechanism Rising concentration inhibit release mechanisms Neuroendocrine Re exes Neural activation can produce a rapid increase in hormone release Diurnal Circadian Secretion Daynight around a day rhythms on a 24 hour cycle Entrained by sleep wake or light dark cycles Night shift work put some pairs of hormones out of cycle increases junk illnesses Recent reports of increased cancer risk possibly due to altered melatonin release Endocrine Disorders Hyposecretion or hypersecretion often related to endocrine or feedback cell receptor malfunction Target cell malfunction no response from normal hormone level Cell Responsiveness Controlled by the number of hormone receptors available on target cell Desensitization due to chronic elevated hormone level Internalization or chemical modification of receptors Type II diabetes has down regulation of insulin receptors Permissiveness One hormone enhances the response of a second hormone TH increases Epinephrine receptor number on target cells Synergism Two hormones increase each others activity FSH and testosterone each help the other increase sperm production Antagonism One hormone reduces the effect of another hormone Progesterone decreases estrogen receptor number on the uterus Pineal Gland Releases melatonin to help regulate circadian rhythms Biological Clock Controlled by the superchiasmic nucleus in the hypothalamus Clock proteins in the SCN regulate their own production over a day Clock proteins control the neural output of the SCN which in turn controls some hormonal outputs like the cortisol External cues keep the SCN on 24 hour rhythm Melatonin Release from Pineal gland is controlled by light M release is high in dark Controls light dark hormonal uctuations May help sleep decrease aging and free radicals slow aging of the immune system link with puberty questionable Plasma Calcium 90 of phosphate stored in bone 99 of calcium stored in bone as calcium phosphate Ca 25 mM in plasma 107 M in cells Regulated by PTH Parathyroid Hormone PTH increases reabsorption of Ca first from bone uid in spaces and then from CaPhos Necessary for life no PTH 9 hypocalcemia Hypocalcemia Low blood calcium Hyperactive nerve and muscle increased Na entry Larynx and diaphragm spasms no air Vitamin D Control of Ca absorption Enhances PTH activity Osteoporosis Decreased estrogen linked to OP PTH Vitamin D Ca all normal Decrease in bone density Less effect when bones are thicker at menopause Weight bearing work and exercise thickens bones L 44 Hypothalamus Pituitary gland Hypothalmus Pituitary Structure H at the base of the brain stalk connects H to Pituitary Posterior Pituitary connected by neural axons Anterior Pituitary connected by Hhypopyseal portal system Vasopressin Secreted when osmolarity increases Increases H20 reabsorption at collecting duct Stimulates aquaporin insertion into CD membrane Oxytocin Contracts uterus during childbirth Causes milk ejection from mammary glands during lactation Hypothalamic Releasing Inhibiting Hormones Anterior pituitary hormone release control by hypothalamus Releasing Inhibiting hormones travel by portal system to Anterior pituitary RH and IH control release of 6 Ant Pit hormones Portal System Connects capillary beds from Hypothalamus to Ant Pit Small distance and no dilution means RH and IH released in very small amounts but with big effects Anterior Pituitary Hormone Release Input to the Hypothalamus controls RH and IH release Input is both neural and hormonal Balance of RH and IH for particular Ant Pit hormone controls Ant Pit hormone release Negative Feedback Anterior Pituitary hormone release is regulated by Negative Feedback always to Ant pit Sometimes to Hypothal Target gland hormone release inhibits Ant pit tropic hormone release Growth Control Multiple factors all necessary for full growth Genetics provides base and maximum Nutrition most important nongenetic factor Proteins vitamins minerals essential for full growth Calories needed Growth can catch up during puberty if decreased in childhood due to protein catabolism during disease injury Growth Hormone Protein from anterior pituitary Activates second messengers at many organ cell membranes 15 min circulation time before metabolism by liver NonGrowth Related Effects Increase liver glucose production Increase fatty acid release from adipose tissue Conserves glucose for brain use during growth GrowthPromoting Actions Hyperplasia more cell division and hypertrophy more filaments of cells Increases protein synthesis Bone Growth Growth hormone stimulates bone thickness and length Bone Composition Outer layers have compact bone CaPhos hardens collagen makes strong and exible Inner layers have spongy bone Long bones epiphyses at both ends diaphysis in middle OsteoblastOsteoclasts O blasts form new bone and secrete calcium phosphate O clasts resorb bone create spaces in bone Bone Length Growth Length growth occurs at epiphyseal plates o clasts eat epiphyses o blasts extend diaphysis Fuse at puberty o blasts catch o clasts Control of Growth Hormone Release Hypothalamus releases both GHRH and GHIH Diurnal Highest an hour after sleep begins Exercise physical stress and low blood glucose increase GH release GH Deficiency In children dwarfism occurs with decreased bone growth No effect on adults GH Excess Before puberty increased proportional growth After puberty acromegaly excess growth of face hands and feet L45 Thyroid Thyroid Hormone Increase metabolic activity in most tissues Decrease TH 9 poor mental health and physical function decrease cold resistance mental retardation in children Increase TH 9 wasting nervousness increase heat production tachycardia Thyroid Hormone Synthesis Protein thyroglobulin made by follicular thyroid cells Exocytosis to colloid iodine added to tytosines Link DIT either DIT or MIT Endocytosis Digestion to T3 or T4 TH Secretion MIT and DIT recycled in follicular cells T3 and T4 secreted into blood Most secretion is T4 TH Transport T3 and T4 circulate bound to protein T4 4000 bound 1 free free is active Most T4 converted to T3 in circulation T3 is more active than T4 TH Buffering As TH lost in urine or to cells other TH come off protein T3 binds weaker than T4 T3 lost faster TH Effects All increase metabolic activity Maximizes GH effects on protein synthesis and bone Calorgenic Increased heat production TH binds to nuclear receptors alters gene activity Increases cell activity increases fatty acid metabolism increases Na pump Sympathomimetic Function Required for full sympathetic response TH stimulated production of adrenergic receptors Heart TH increase in adrenergic receptors Increases heart rate and force of contraction Neural Tissue Needed for CNS development in children TH required for full neural function response to catecholamines RAS function Cortex and basal ganglia need TH Regulation of TH Secretion By Thyroid Stimulating Hormone TSH from anterior pituitary TSH Regulation Decrease blood TH 9 release of TSH from anterior pituitary TSH go to thyroid gland 9 increase thyroglobulin secretion Endocytosis and T3 T4 production Hypothyroidism Thyroid gland disease or decrease TSH production or autoimmune attack Decrease BMR lethargy decrease mental and physical activity Graves Disease Hyperthyroidism 9 nervousness weight loss warmth increase BMR exopthalamus bulging eyes Cause is antibody TSI that binds and activates TSH receptors increase thyroid gland activity Hashimoto s Syndrome Autoimmune attack on thyroid gland decreases function Hpthyroidism need synthetic TH not rare Goiter Enlarged thyroid gland Due to excess TSH or TSI May produce hypo from decrease iodine or hyperthyroidism from increased TSI L 46 Adrenal Gland Adrenal Medulla Inner later of adrenal gland Similar to postganglionic sympathetic neuron Secretions Stored in granules Epi NE 41 strong peripheral effects Vitamin C is released with Epi NE Vitamin C prevents oxidation prolonging effects of Epi NE Effects of Catecholamines Epi increases HR decreases HR decreases TPR increases CO NE increases vasoconstriction except in heart and skeletal muscle Net effects is huge increase in BP increase in metabolic rate Neural Control Release determined by baroreceptor activity Decrease BP 9 increase EpiNE release Increase BP 9 decrease Epi NE release Adrenal Cortex Outer layers of adrenal gland Endocrine gland Secretions Released as made not stored All are steroid derivatives of cholesterol Mineralocorticoids aldosterone at al Glucocorticoids cortisol at al Androgens DHEA androstenedione ACTH Effects and Control ACTH from anterior pituitary when cortisol is low stress is high on top of diurnal rhythm ACTH causes increase of all adrenal cortex steroids except aldosterone Circulation of Glucocorticoids Most bound to globulin proteins Only free form is active Activity of steroids last 1 hour Glucocorticoids Effects Cortisol is stress hormone necessary for survival Bind to nuclear receptors to increase protein synthesis Metabolism Increase protein catabolism freeing amino acids for damage repair Increase plasma glucose Increase plasma fatty acids Glucose and fatty acids provide energy for repair Permissive Actions Assists actions of glucagon and catecholamines vasoconstriction bronchodilation Stress Something is only a stress if ACTH increases ACTH 9 increase cortisol release Short term 9 increase energy availability amino acid availability catecholamines Long term stress harmful excess protein breakdown wasting pain Anti In ammatory Effects Only at high glucocorticoid levels Decrease swelling decreases histamine Also blocks immune system Apoptosis of WBCs Must use antibiotics to prevent infection Not for routine use Mineralocorticoids Aldosterone increases Na reabsorption in the kidney Adrenal Androgens Major effects in females No or minor effects in males DHEA Sex drive and starts growth spurt at puberty in females Estrogen caps female growth spurt No effect in males testosterone is 100x stronger Androstenedione Little affect itself precursor to testosterone and estradiol L 47 Fuel Metabolism Insulin Diabetes AnabolismCatabolism Balance of buildup of large macromolecules with breakdown Controlled by activity and energy balance Essential Nutrients Some nutrients cannot be made in the body Some amino acids and all vitamins must be in diet Nutrient Storage Glycogen storage in muscle and liver Fat storage in adipose tissue Body will consume muscle for amino acids during starvation Brain Glucose Supply Brain only uses glucose for energy liver glycogen maintains plasma glucose between meals Fats cannot be made into glucose cannot supply energy to brain If no glucose available body converts protein to amino acids to glucose Absorptive State Postmeal state several hours after eating Many nutrients available from newly arrived meal Absorption of carbohydrates then protein the fats Post Absorptive State Between meals fasting Use stored energy to supply tissues energy needs Islet Cells In pancreas secrete hormones into blood Alpha cells secrete glucagon Beta cells secrete insulin Secretion Increase plasma glucose 9 increase insulin secretion Leave capillaries through pores Insulin Effects All aimed at storing energy for future use Decrease blood glucose level Carbohydrates Seconds increase of glucose transporters by fusion of membrane transporter vesicles Increase glucose entry into cells Brain and working skeletal muscle don t need I Minutes increase glycogen storage in liver and muscle Fats Hours increase lipid storage Proteins Seconds increase amino acid entry into cells Minutes increase liver glycogen strong enzymes and protein synthesis Regulation of Insulin Secretion Increase plasma glucose 9 increase insulin release 1 hour Decreased glucose causes decreased insulin release Sugar meal has rapid rise and fall in glucose I stays high Hypoglycemia after sugar meal as I stays high after sugar transport complete Starch meal takes longer to ingest glucose glucose and insulin never get as high no hypoglycemia Glucagon Increase blood glucose level Opposite effect of insulin Increase glycogen breakdown liberates glucose from storage Increase lipid release increase glucose production by liver Decrease plasma glucose 9 increase glucagon release Increase plasma glucose 9 decrease glucagon release Other hormones Epi cortisol also cause increase plasma glucose Diabetes Mellitus Glucose in urine Type I 10 autoimmune attack on beta cells Type II 90 obesity and age decrease ofI receptors Hyperglycemia Increase plasma glucose Hemoglobin a1c test long term glucose indicator Increase blood osmolarity 9 exceeds Tm for glucose Dehydration Increase urine volume Loss of Na and K Decrease blood volume 9 decrease BP 9 shock 9 death Protein Metabolism Amino acids used for energy and to make glucose in liver Negative protein balance and wasting Fat Utilization Use fats for energy in insulin dependent tissue most Fat use increase plasma fatty acids and cholesterol 9 increase atherosclerosis Acidosis Fat metabolism 9 increase ketone bodies 4C keto acids Increase ketosis 9 increase acidosis 9 increase breathing rate decrease mental activity Coma Acidosis dehydration hyperosmolarity from extra glucose can all induce coma in diabetics and some come leads to death Type I Diabetes Mellitus Juvenile Diabetes Most prominent in teens but can occur at other ages Autoimmune Attack Immune attack gradually destroys beta cells over a few years Gradual loss of insulin production hyperglycemia develops Type II Diabetes Mellitus Loss of insulin receptors Associated with obesity in people under 40 Symptoms like Type I Obesity Prolonged elevated glucose 9 constant insulin production Elevated insulin 9 down regulation of insulin receptors 9 decrease glucose entry and hyperglycemia Reducing caloric intake helps Age In elderly people decrease receptor or receptor availability Not necessarily associated with obesity but increased weight can increase probability May take some insulin to maximize available receptors L 48 Cancer Incidence Males prostate gtlunggtcolongtbladder Females breastgtlunggtcolongtuterine Incidence declining 2 year since 1992 Cancer deaths largest number with percent of incidence deaths Males lung 100gtprostate 16gtcolon 45gtpancreas 100 Females lung 90gtbreast 22gtcolon 45gtpancreas 100 Types Separated by ability to spread Benign Localized can produce problems if tumor crushes adjacent tissues or draws blood from adjacent tissues Treat with surgery Many benign tumors are not cancerous Malignant Has metastasized trough lymph system Surgery to remove large tumors chemo and radiation to kill spread cells Diagnosis Need biopsy for full diagnosis increasing use of MRI Tumors often produce hormonal or protein markers Treatments Combinations of treatments will vary with different cancers Surgery Remove tumor and some surrounding tissue to make sure all tumor removed Radiation Kills fast growing cells damages DNA and makes oxygen radicals Side effects on bone marrow and GI tract Chemotherapy Kills fast growing cells multiple targets DNA and mitotic spindle main ones Also bone marrow and GI side effects Biologic Therapy Shift host tumor balance toward host Alter T cell antibody production and cytokines to attack tumor Genetics Single cell generates tumor Not inherited from parents Even predisposition needs additional mutations Mutation DNA alterations lead to unrestrained cell proliferation mitosis Tumor Viruses Only a few cancers are linked to viruses DNA RNA viruses alter DNA in host cell Only RNA virus cancer is a type of leukemia DNA viruses have several links cervical cancer liver cancer lymphomas during immune deficiency Cell Biology Uncontrolled growth due to cell changes 1 mutation not enough malignancy usually needs 5 to 10 p53 Mutations p53 pathway controls normal mitosis acts as tumor suppressor Many but not all tumors have p53 mutations Mutation leads to genomic instability and resistance to Apoptosis Environmental Signals Effects occur in cancer cells after mutations Cytokines and Paracrines alter G protein and enzyme linked processes Effect signals to genome that regulate mitosis Loss of cellcell connections and contact inhibition Transcription Factors Control gene activation alteration in genes and or factors Factors affect expression in tumor cells allowing tumor growth Apoptosis Regulation Programmed cell death often occurs after mutation Caspases are enzymes controlling apoptosis attack DNA enzymes cytoskeleton Decreased caspase activity in tumors Target of new cancer treatments Angiogenesis Tumors draw blood from surrounding healthy tissues starving them Prevention Prevent the multiple mutations necessary to start tumor Smoking Cessation Stopping is the single most positive health activity 400000 premature deaths year from smoking Smoking linked to lung larynx esophagus bladder pancreatic cancers Also linked to cardiovascular and pulmonary disease 90 who quit do so on their own total quitting most successful Diet Decreased fat intake decreases cancer rate Anticarcinogens in vegetables fruits nuts Fiber decreases colon cancer Sun Avoidance UV radiation causes an increase in skin cancer Acute sunburns even in childhood increase risk of melanoma Lighter skinned people have greater risk Chemoprevention New field drugs designed to decrease mutation risk Antimutagenic antioxidant antiproliferative preventatives OFTEN significant side effects Use of tamoxifen to decrease breast cancer in highrisk women May increase cervical cancer risk balance risk L49 Sex Differentiation Male Reproductive System Chromosomes 23 pairs 23 from mother 22 X 23 from father 22 X or Y Carry genes code for proteins X and Y Chromosomes XX is female XY is male X chromosome is large many genes Y chromosome is small few genes SRY gene starts male development in utero Gonads in Embryo Gonads are the testes and ovaries At 7th week with SRY gonadal medulla 9 testes cortex regresses Without SRY gonadal cortex 9 ovaries medulla regresses Puberty Maturation of reproductive system Females hair pattern breast development and menstruation Males hair pattern erectile function sperm musculature Onset Increased Gonadotropic RH GnRH release from hypothalamus necessary Kisspeptin stimulated Increased release of FSH and LH from pituitary Leptin from adipose tissue may be necessary for menarche onset of menstration Pituitary Gonadotropins FSH LH Need GnRH from hypothalamus for release Controlled by negative feedback of gonadal hormones testosterone estrogen progesterone FSH Follicle stimulating hormone Females growth and activation of ovarian follicles Males develop and mature sperm by activating Sertoli cells LH Lutenizing hormone Females ovarian maturation estrogen secretion ovulation Males testosterone secretion from Leydig cells Testes Seminiferous tubules sites of sperm production Lydig cells testosterone production Spermatogensis Formation of sperm cells from spermatocytes 1OO million sperm day Sperm Formation Spermatogonium mitosis one stays one migrates inward Migrating cell spermatocyte remodeled to sperm cell Sertoli cells absorb most of spermatocyte cytoplasm Sperm Structure Head acrosome digestive enzymesnucleus23 chrom Midpiece mitochondria Tail propulsion by microtubule rotation only needed near ovum Temperature Maximum sperm production at 32C body is 37C Scrotum will rise in cold and descend in heat to maintain temp Nondescended testicles usually sterile Semen Liquid holding sperm 3 ml ejaculate 300000000 sperm lt20000 sperm ejaculate considered sterile Accessory structures contribute fructose mucus clotting proteins bicarbonate to semen Erection Arteriole dilation venous compression 9 engorgement Parasympathetic n 9 NO production 9 arteriole vasodilation Emission Mixing of prostatic uid sperm and seminal vesicle uid just prior ejaculation Sympathetic n control emission Ejaculation Skeletal contraction expelling sperm Testosterone Steroid hormone Released in utero and shortly after birth to create male reproductive system No further release until puberty Tonic release thereafter Secretion From Leydig cells as made 98 bound to protein in circulation 2 free and active Stimulates protein synthesis Secondary Sex Characteristics Male hair pattern penile and genitalia enlargement Vocal cord thickening increased mental acuity Increased sex drive increased growth Anabolic Effects Growth spurt then epiphyseal closure Increased musculature and kidney size Inhibin Released from Sertoli cells Inhibits FSH release All hormones are tonic and stable after puberty L50 Female Reproductive System Menstrual Cycle 2135 days variable 28 days average Some women regular others irregular Ovum prepared for release from follicle Uterus prepared for implantation of embryo Ovarian Cycle Ovum growth release follicular change Follicular Phase Days 114 dominated by FSH stimulation Several follicles enlarge and form antrum One follicle outgrows others which regress in size atresia Estrogen released from granulose and thecal cells surrounding ovum Ovulation 14th day High levels of Estrogen stimulate Kisspeptin release from the Hypothalamus Kisspetin stimulates GnRH release which stimulates the LH surge LH surge from anterior pituitary ruptures antrum Ovum released into abdomen fimbria sweep ovum into oviduct Ovum surrounded by granulosa and thecal cells and zona pellucida gel Luteal Phase Days 14 28 Corpus Luteum forms from remaining cells in ruptured follicle CL secrete progesterone and estrogen pepares uterus for implantation Uterine Cycle Site of fetal growth Changes will supply implanted embryo with energy until placenta develops Proliferative Phase Days 514 Variable part of cycle Repair of uterine surface after menstruation Secretory Phase Days 1428 Uterine lining greatly increases vascularization and thickness P decreases uterine contractions Uterus secretes glycogen for embryo Menstruation Days 15 Sloughing off of uterine lining if no implantation Cervix Opening between vagina and uterus Usually blocked with mucus prevents infection lets sperm in lessens acid killing of sperm Indicators of Ovulation Increase basal body temperature by increasing progesterone Thinning of cervical mucus Fertilization range 3 days 2 days before ovulation sperm lifetime to one day after ovulation fertilizatable ovum Ovarian Hormones Estrogen and progesterone have multiple effects Estrogens Formed from androgens testosterone and androstenedione from thecal cells Thecal and granulose cells produce estrogen Effects of Estrogens Increases follicular development Increases Ciliary motion in oviducts increase uterine muscle size thins cervical mucus Kisspeptin release at ovulation increase neural plasticity increase sex drive Progesterone Increase secretions and size of uterus increase breast development Increase cervical mucus Decrease contractions during pregnancy increase heat production Relaxin Hormone from ovaries and placenta Helps sperm penetrate ovum membrane Increases digestion of connective tissue Softens pelvis and cervix for delivery Menopause 4OO cycles in females 1400 of 7 million oocytes develop per cycle Only one ovum released the remainder undergo atresia Decline and loss of estrogen and progesterone when oocytes gone Osteoporosis Decreased estrogen linked to OP PTH Vitamin D Ca all normal Decrease in bone density Less effect when bones are thicker at menopause Weight bearing work and exercise thickens bones Cardiovascular Effects Increases in CV disease after menopause Decreased HDL increased vascular reactivity with decreased estrogen Increase in BP Hormone Replacement Designed to help decrease menopause symptoms such as hot ashes Recent links slight increase in heart disease stroke breast cancer Increased caution balance riskbenefit L51 Pregnancy Lactation In oviduct Capacitation increase sperm motility occurs in female reproductive tract Chemical attraction of sperm to ovum Head of sperm attaches to zona pellucida receptors Digestive enzymes in acrosome breakdown zona pellucida Sperm enters ZP receptors blocked blocks second entry Embryo Development Ovum starts dividing after fertilization 9 blastocyst still surrounded by other cells form trophoblast In uterus trophoblast implants in uterine wall become placenta Folic acid needed for proper embryonic development Corpus Luteum hCG from uterus maintains corpus luteum Continues progesterone production until placenta large enough for progesterone production Placental Hormones Function to maintain pregnancy hCG human chorionic gonadotropic Maintains CL after implantation Used for pregnancy tests Progesterone Decreases uterine contractions during gestation Decrease in P triggers start of contraction at parturition Relaxin Also decreases uterine contractions Softens pelvis and cervix for delivery Placental Functions Supply steroids for fetal cortisol Exchange of gases nutrients waste products Increase maternal respiration and renal output Parturition Childbirth Exact initiator unknown Increase estrogen 9 increase uterine excitability increase of gap junctions and increase of oxytocin receptors Progesterone Decreases in most cases In some deliveries other factors overcome quieting effect of P on uterus Oxytocin 0 levels high throughout pregnancy but low of receptors Increase of receptors near term estrogen effect Increase uterine contractions and cervical dilation Labor Positive feedback increase uterine pressure 9 oxytocin release 9 increase pressure 999 increase prostaglandin release 9 increase oxytocin induced contractions Spinal re ex aids delivery by increasing abdominal contractions Head first then shoulders rest of body placenta Lactation Milk production for newborn nutrition Prolactin PRL Not a gonadotropin does not cause hormone release Females milk secretion PRL secretion peaks at parturition Breast Development Estrogen increases mammary duct size Progesterone increase mammary lobule size PRL completes structural development Milk Secretion Primarily by PRL First 2 weeks are colostrum nutrients lactoferrin antibiotic antibodies Then milk includes all essential nutrients Milk Ejection Increase in oxytocin triggered by suckling Contracts mammary ducts Milk to nipple lapped up not sucked out Oxytocin increases uterine contractions returns to shape GnRH Effects Prolactin decreases GnRH release Decrease FSH decrease LH decrease ovulation during breast feeding duration Exam Review L1 Molecules Cells Tissues Negative Feedback Positive Feedback rare state change and stays there How they apply and relate to each other L2 Ribosomes Attached to ER Link up Amino Acids Order Determined from Most of proteins fold up to right orientation ER Rough endoplasmic Smooth endoplasmic Lysosomes Break down materials Endocytosis L3 ATP Money alters molecules by adding phosphate by Glycolosis ATP keep it going NAH NADH lactate from exercise Mitochondria Aerobic energy Fats enter as 2 carbon units Microtubules Structure shape Movement around cells Kinesin dynein Causes parts of cells to move Cilia Flagena Cleaning out lungs ovum present only on sperm tail driven by microtubules and motor proteins L4 Phospholips Basis for membranes producing lipid billayer that hydrophilic molecules can t cross Allows them to adhere to outside Hydophobic get through water not membrane need transport Hydrophilic cross membranes but piggy backs on albumins Cholesterol Provides stability so cells don t rupture Receptors Chanels Membrane Membrane proteins receptors binds channel or enzyme Tight Iunctions Produce surface that separates tissue with different parts of body digestive skin Gap Iunctions Heart smooth muscle L5 Ficks law of diffusion Elements what cause rate to go up or down Osmosis Details of carrier transport Facilitated Diffusion carrier to go to high conc To low Active Transport move ions against gradient moving them against gradient Sodium ATP energy consumer Secondary Active Transport hydrophilic use sodium L6 Permeability Sodium or Potassium determines membrane Potential 90 60 Resting membrane potential Hyper Graded Potential sensory tissues prop To stimulus Voltage gated channels Open simotaneously travels from one end to another Depolarization graded potential AP spike Dendrites Function most of input to neuron lots of receptors sinapses send info into cells Myelin Nodes of Ranvier increases rate of AP faster speed Refractory period limit on neurons and muscle activation L7 Components of Presynaptic neurons Calcium causes exocytosis Neurotransmitter into cleft Vesicles EPSPS Leading toward threshold IPSPS Majority of synapses in brain Axon Hillock high concentration of voltage gated Na channels Temporal summations Spatial summation L9 Paracrines local hormone in one place activation that alters activity of cell right next door Hydrophilic bind to receptors that produce second messengers CyclicANP activate kinases with cascades and amplifies Calcium acts as 2nd1 messenger and turns on enzymes GProteins over 800 alter activity in circadian rhythms change activity over time Afferent neurons in Efferent neurons out types para sym som Glidal Cells Astrocytes apendable cytes Plasticity brain can form new synapses Language Control Wernickes Brokes area Hemispheres Genius uses both L11 Basal Nuclei balance Thalamus editor for sensory info into brain to cortex Decision cortical Limbic system detects emotions Cortex response Short term turnover of existing mem in hypocampus Long term new synapses in temporal mem rem sleep Working compare new to current Cerebellum basis balance coordination Vision aim Sleep slow wave sleep 4 stages to rem REM paradoxical sleep produce long term plasiticity Most likely to waken self Re exes Re ex Arc input to system withdrawal re ex and pain interneurons Stretch Re ex no neural control Types of receptors Physical touch hearing Chemical taste smell 4 Receptor Potentials not AP Magnitude stimulus Phasic receptors adapt quick Tonic slow balance vision Slow pain cancer breaking down proteins substance P Smell more exceptions than any other system adaptation tonic Lense Ciliary Body controls thickness of lens by contracting and releaxing COroid absorbs stray light to focus Photoreceptors rods and cones Bipolar edge Ganglion cells leave eye to carry into brain Color Vision opsins 3 color blindness missing opsin Ear bones tympanic membrane to oval window amplification Eustachion tube drains uid Basalar membrane hair cells tectorial membrane Hammer overtones Linear acceleration determine what direction moving Next lecture Sympathetic responses Receptor types Alpha beta1 beta 2 Parasym responses ACT release Endplate potential always bigger contrast to EPSP Contraction and relaxation continue to cycle NEXT lecture Sarcomere shortening force Thin and thick filament Functions of t tubule sarcoplasmic ret calcium Troponin calcium binding Tropomyosin shift Force generation PI released Filament sliding dec force on cross briges Next lect Forces Length tens falloff at long lengths Effects of stretching muscle Power curve max power at 25 Muscle can resist up to 15x NEXT L Phophocreatine PI increases Glycolysis acidosis Diff bet Red and white fibers Cause of hypertrophy partially broken filaments Bag fibers Nuclear chain fibers Golgi tendon organ monitors force NEXTL Dense bodies anchor thin filaments Tone CA contraction no stimulus Myosin Light chain activate smooth muscke Latch Visceral smooth muscle tissues that empty content uterus dig tract L 21 Intercalated disks desmosomes gap junctions SA Node initiate heartbeat AV Node atria to ventricles Purkinje Fibers Ventricular mucles plateau phase because of calcium Pacemaker cells Sym and para alters those EKG P wave activates atria amp T wave repolarization of ventricle NEXT L Diastole rest phase Vent Systole heart empties Aortic pressure limits on energy Cardiac output how it changes stroke volum x heart rate Starlings law more venous return causes more efficient contraction NEXT L In uence of vessel radius Variable In uence of viscosity Effect of EPO on raising RBC Coronary Diastole Astherosclorosis stage 1 reversed in alcohol NEXT L Filtration Forcing sluid out t h rough pores Reabsorption due to pr oteins Return of filtered more filtered BP drops if not returned Edema swelling quot Vericose veins lose valves decrease return of blood Plasma proteins albumins fibr RBC functions production Hemoglobin 4 parts iron atom in middle and 02 Platelets pinched off pieces of ka Platelet plug from ADP prevented by releasing prostycyclin from health endo cells Coagulation formed by fibrin bloack rupture blood vessel Intrinsic Extrinsic more common NEXT L Neutrophils Mono Basophils Complement system Pore formation Histamine increase poor size increase blood Fighting off something Plasma cells lots of ER Primary response slow small short Secondary fast large long Antibody functions L 28 Helper T cells Activate immune system cytokines help diff between Class 1 and class 2 MHC what cuases immediate hypersensitivity delayed sensitivity generalities of skin L 29 Type 1 and Type 2 cells 1 barrier 2 surfactant 3 pressures how they relate to another Boyles Law Inspiration triggered by contractions of diaph Alveolar surface tension Broke by surfactant Anatomical dead space L 30 Diffusion across alveolar wall Oxygen transport Hemoglobin binding curve steep in blood stream C02 effects 2 effects Perm binding to hemoglobin shifting curve C02 transport 3 ways Hypercapnia Medullary control centers Chemical control of respiration SIDS best on backs babys Neumothorax pressure equalizaed Emphysema causes Nephron Glumerealar filtration 125 decrease over long time Inulin measures Glucosuria 3X Sodium Reabsorption Cotransport Causes glucose reabsorptioin Effects of Ang 2 ACE inhibitors treats hypertension PAH measures Renal blood ow Loop of Henle creates gradient Vassopressin inserts aquaporins Aquaporins Urine buffering Affects of Aldosterone increase NA Ureter entry sqeezed shut by bladder wall sphincters L 35 Relationship Intra extra plasma interstitial uid Autotransfusoin Blood pressure control Aldosterone long term Tonicity Shrink swell worse Osmoreceptors in hypothalamus 0 release vasopressin Function of Ph acidosis decrease neural acitivy Resp and kidney control getting rid of H ions Acid Base imbalance resp acid Met alk Metablic vasodilarors Baroreceptors Input to medulla Cardiac effects Alpha and beta receptors L 38 Complex carbs enzymes amal disac Protein digestion Proenzymes Peptidases Lipases in active form from pancreas Micelles Portal Vein function Vitamins B amp C Different GI layers mucosa important Basic Electrial rhythem MMC GI hormones KNOW ALL Secretions of mouth Acid re ux Secretions of stomach 3 min How it empties Alkaline secretion Blood supply Bilirubin metabolism Villi microvilli Diahrheea cuase SI origin Gastroilleal re ex Bacteria Defacation Final Exam Review Oxidative Phosphorylation Electron Transport System Hydrogen split used to pump protons out proton gradient reduced ATP electron oxygen water Thyroid Hormone Synthesis Stimulated by thyroid stimulating hormone starting precursor thyroid globulin chop it into little bits and add iodine s MIT DIT of iodine s put them together T3 or T4 Make more T4 T3 more active so hydrophobic they bind to proteins 40001 only the stuff in the blood bind to receptors Hashimotos syndrome synthetic THS PPY stimulated by ghrelin released by the brain appetite suppressing CCK appetite suppressing out of the duodenum Effects of Catecholamines Epi Nore Stored and released with Vitamin C keeps them from oxidizing TPR total peripheral resistance Epi increase heart rate increase heart rate vasoconstrictor to G1 digestive system vasodilate to skeletal muscles heart Hypothalamus Pituitary Growth Negative Feedback from Anterior Pituitary feedback to the gland that made it and to hypothalamus Glucocorticoids steroids Cortisol cortisone Comes from ACTH that goes to adrenal cortex which releases it Increase protein synthesis increase glucose production Suppresses immune function Anti In ammatory Increases protein synthesis Regulation of Insulin secretion Stimulator high blood glucose insertion of glucose transporters Tissues that don t need insulin brain working skeletal muscle Insulin level stays up after high sugar meal Sustained energy complex sugars Glucagon Stimulator low blood glucose Kispeptin initiates menstruation and comes from the Hypothalamus Follicular Phase Lutear Phase ovarian phase Getting the ova egg to be released Follicular phase is the first half with each menstrual cycle follicular stimulating hormone causes the 7milllion4OO to start maturing Estrogen Inhibits early on Then Estrogen Stimulates The cells left after the release are the luteum Lutear Phase Corpius Luteum secretes progesterone Progesterone maintains the uterus If fertilizes zygote HCG maintains corpeus luteum and stays around for 3 months making progesterone HCG goes away after 1St trimester and placenta takes over FSH causes follicular stimulation rise early in cycle then goes away LH relatively low and spikes on the day of ovulation then goes away rupture one follicle Cell Responsiveness Down Regulation chronic exposure reduced response Some cases chemical internalization Permissiveness One increases the other Thyroid hormone and adrenergic receptors epinephrine Antagonism Both reduce the response to each other Synergism Both hormones increase each other Transcription Factor Has to be activated to get a particular gene to be made Ex Cortisol needs to bind to a receptor which will bind to a gene and make transcription Melatonin Release from the Pineal gland regulates Circadian Rhythms Insulin Effects Not glucose specific Micronutrients into storage glucose is the first responding nutrient Minutes storage of sugars Multiple Minutes proteins Hours fats Force generation amp filament sliding Myosin already bound to actin Myosin head can hydrolyze ATP and turn it into ADP amp Pi Force from ejecting Pi causing the protein to change Filament sliding is because of the force and muscle contraction Tropomyosin in the way of actin Calcium binds to tropONin Desmosomes cellular rivets Starlings Law More blood coming into heart stretching the heart going up the pressure volume curve Increase venous return Fat Utilization Fatty acid organic chains exist as an even of carbons 141618 long 2 carbons to become ACET co a One capillary to another capillary by portal vein Hypothalamus to anterior pituitary Releasing hormones travel through Minute quantities big effects GFR PAH regulated by renal blood ow Inulin only filtered Filtration Fraction Ratio of inulin to PAH MHC Class 1Class 2 Class 1 present self antigens usually 4 of them Class 2 foreign antigens warns immune system tells it you are you Control of the Adrenal Medulla Sympathetic Neuron Nerves that go to a particular spot Dumps Epinephrine Norepinephrine Also get Vitamin C ACTH Adrenal Medulla Muscle Sarcomere smallest functional unit of muscle Thick and thin filaments anchored on 2 lines crossbridges calcium ATP force Filaments slide to decrease force and sarcomere contracts and filaments overlap but gets taller
Are you sure you want to buy this material for
You're already Subscribed!
Looks like you've already subscribed to StudySoup, you won't need to purchase another subscription to get this material. To access this material simply click 'View Full Document'