BME 311 Final Exam Study Guide PDF

Semester Overview Topic List Exam 1: Lecture Notes 9/3 Nernst potential (equilibrium potential): theoretical intracellular electrical potential that would be equal in magnitude but opposite in direction to the concentration force Concentration gradient AND electrical potential Nernst Equatio...

Semester Overview Topic List Exam 1: Lecture Notes 9/3 Nernst potential (equilibrium potential): theoretical intracellular electrical potential that would be equal in magnitude but opposite in direction to the concentration force Concentration gradient AND electrical potential Nernst Equation for Equilibrium Potential EK: EMF (mv) = - 61 log (Ci / Co) i inside o outside Ex. If Ko = 4 mM and Ki = 140 mM Ek = -94 mV If the membrane were permeable to only K+, Vm would be -94 mV Membranes and Action Potentials Inside (mM) vs Outside (mM) Na+ 14 inside 142 outside 156 K+ 140 4 144 Ca2+ 0.0001 1 1.0001 (-61/2) Cl- 10 110 120 H+ pH 7.2 pH 7.4 Mg2+ 0.5 1-2 HCO3- 10 28 SO42- 2 1 PO3- 75 4 Protein 40 5 Active Transport Na+/K+ ATPase Sodium Potassium Pump Sodium out, potassium in K+ inside, Na+ outside K+ pumped in, Na+ pumped out Majority of cells are negative on inside and positive on outside (like depressed people) Lecture Notes 9/5 Inside is negative and outside is positively charged, relatively 3 Sodium Na pumped outside, 2 Potassium K pumped in Think of depressed person: positive on the outside, but negative on the inside Log of a fraction bigger than 1 is positive Log of a fraction less than 1 is negative log(0.01) is -2 log(0.1) is -1 log(1) is 0 log(10) is 1 log(100) is 2 Since Calcium has a +2 charge, the Nernst equation is + 61/2*log(Cai/Cao) Nernst Equation for Equilibrium Potential Vm: EMF (mv) = - 61 log (Ci / Co) Multiple ions: Negative and positive ions flip in and out For example, could do K+ inside on top, Na+, inside on top, Cl- outside on top By convention, use positive ions as inside on top, outside on bottom and negative ions as outside on top, inside on bottom Ex. Vm = -61*log( PK[K+]in + PNa[Na+]in + PCl[Cl-]out / P’K[K+]out + P’Na[Na+]out + P’Cl[Cl-]in ) P ~ permeability Ions are diffusing in different amounts at different moments in time The resting membrane potential is closest to the equilibrium potential for the ion with the highest permeability Sodium Nernst potential +61 mV Potassium Nernst potential -94 mV Calcium Nernst potential +130 mV Chlorine Nernst potential -65 mV Resting membrane potential: Membrane potential due to diffusion of a single ion can be modeled by the Nernst equation, for K+ ions Goldman Constant Field Equation is for multiple ions: Vm = -61*log( PK[K+]in + PNa[Na+]in + PCl[Cl-]out / P’K[K+]out + P’Na[Na+]out + P’Cl[Cl-]in ) Depolarization Approach 0 mV More excitable Hyperpolarization Go further away from 0 mV Less excitable Overshoot, positive to 0 mV Positive to 0 mV Repolarization, toward resting potential Threshold (for AP generation) Polarized because resting potentials are away from 0 Resting potential increases going toward 0 Action Potential (AP) Regenerating depolarization of membrane potential that propagates along an excitable membrane All or none events that need to meet the threshold Have constant amplitude and do not summate Initiated by depolarization Involve changes in channel permeability Dependent on voltage-gated ion channels Sodium pumped out, potassium pumped in When potassium ions (inside cell) have potassium gates opened, they shoot out and cause the spike in the potential - Contraction of Skeletal Muscle - Muscles composed of fibers composed of fibers composed of sarcomeres - Muscle cells - Single cells - Multinucleated - Surrounded by the sarcolemma - Myofibrils - Bunch of myofilaments - Contractile elements - Surrounded by the sarcoplasm - Actin Filaments - Actin filaments are tethered at one end of the sarcomere at the Z disc - Double stranded helix - Composed of polymerized G-actin (active sites) - Myosin heads bind to active sites - Troponin - Binding of Ca2+ to troponin results in a conformational change in tropomyosin - Tropomyosin - Covers active sites  - Prevents interaction with myosin (when Ca2+ is not present) - The Myosin Molecule - The head region is the site of ATPase activity - Figures in the book - Fuzzy parts of thick myosin are where binding occurs to sliding thin actin filaments as they move. Need Calcium to bind to troponin to uncover those tropomyosin binding sites and begin walking along, causing contraction Lecture Notes 9/9 - Mechanism of Muscle Contraction - Binding of Ca2+ to troponin results in a conformational change in tropomyosin that uncovers active sites and allows myosin heads to bind on - Walk Along Theory/Hypothesis - 1. Starting at a strongly bound rigor state. ATP binds to Myosin and lowers affinity for actin. Weak binding site. Starting attached, but then releases - 2. Myosin unclicks from actin filament; the detached state is the beginning of recovery stroke. It pops off. When ATP and phosphate pop off, the head of the myosin clicks down. They cannot connect and cannot open the active sites - 3. Relaxed state; Myosin head changes its conformation and its actin binding. Recovery stroke. Head of myosin further clicks down; unconnected; ready to make a contraction, but cannot bind without Calcium; primed and ready (alternate start) - 4. “Recharged” (with Calcium binds to troponin) myosin binds back onto actin. Binds back onto actin on the thin filament; weak binding state - 5. Once Calcium connects, cue for phosphate to release and ADP to move. Head of myosin clicks back to a straight line; strong binding state - 6. Strong binding state is converted to strong binding state from which ADP associates - 7. ADP is released to produce the strongly bound rigor state; rigor state and rigor mortis after death FIND PHOTO - Passive tension is tension required to extend a resting muscle - Total tension: active tension + passive tension - Active is measured: AT = TT - PT - Normal operating range is at max total tension around 1 resting length  - Single Motor Unit (SMU) - A single motor neuron and all muscle fibers it innervates - Muscle Contraction - force summation - Motor neurons stimulate muscles - Multiple fiber summation: increased contraction intensity from an increase in the number of motor units contracting simultaneously, fiber recruitment - Little stimulation → some amount of force - Increased stimulation → increased force - Frequency summation: increased contraction intensity from increase in the frequency of contraction of motor units - How many stimuli per unit time Lecture Notes 9/12 - - Action potentials approach Nernst potential of potassium on the way up - More permeable to potassium - Sodium channels open on the way up and membrane becomes selectively permeable to sodium - Potassium channels open on the way down and membrane becomes selectively permeable to potassium - Muscle Contraction - Motor unit is a motor neuron and all the fibers it innervates - Multiple fiber summation: increased contraction intensity from an increase in the number of motor units contracting simultaneously, fiber recruitment - More force from more motor units stimulated - Frequency summation: increased contraction intensity from increase in the frequency of contraction of motor units  - More force from more frequent stimulation of motor units - Fast twitch, slow twitch, intermediate - If the muscle is stimulated before complete relaxation has occurred the new twitch will sum with the previous contraction - Muscle Remodelling - Lengthening - Normal - Growth spurts, etc - Occurs with normal growth - No change in force development - Hypertrophy (over + growth) - Common, weeks - Caused by near maximal force development - Ex. weight lifting - Increase in actin and myosin - Myofibrils split - Hyperplasia - Rare - Formation of new muscle fibers - Can be caused by endurance training - Atrophy - Muscles shrinks over time - Over months, muscles become thinner - Over years, fibers start to fall apart - Causes - Denervation/neuropathy - Sedentary lifestyle - Plaster cast - Space flight (zero gravity) - Muscle performance - Degeneration of contractile proteins - Decreased max force of contraction - Decreased velocity of contraction - With fiber loss  - Disuse for 1-2 years - Very difficult to replace lost fibers - Neuromuscular Transmission - Neuromuscular junction: specialized synapse between a motoneuron and a muscle fiber - Motor plate sits on top of muscle - Synaptic trough: invagination in the motor end plate membrane - Little indent in muscle surface for axon terminal - Motor neuron communicates to subneural clefts with acetylcholine - Synaptic cleft: contains large quantities of acetylcholinesterase - Communication done with acetylcholine - ACh release - Action potentials rush in (Ca in and K out), Calcium rushes in, ACh rushes out - Ca2+ channels are localized pre synaptic membranes. Vesicles fuse with the membrane in the region - ACh receipts located at the top of the subneural clefts - End Plate Potential and Action Potential - ACh released into the neuromuscular junction binds to, and opens ACh receptor channels, allowing Na+ and K+ to flow - Acetylcholinesterase terminates the process - Breaking up ACh - Some parts get reabsorbed into neuron - Drug Effect on End Plate Potential Inhibitors - Curariform drugs - Block ACh channels by competing for ACh binding site - Reduces amplitude of end plate potential therefore, no AP - Botulinum toxin - Decreases the release of ACh from nerve terminals - Insufficient stimulus to initiate an AP - - Ach-like drugs: (methacholine, carbachol, nicotine) - Bind and activate ACh receptors - Not destroyed by AchE, resulting in a prolonged ACh effect - Anti-AchE: such as diisopropyl fluorophosphate (nerve gas) blocks the degradation of Ach, resulting in a prolongation of Ach activity - - Extraction Contraction Coupling: Skeletal Muscles - Steps: - 1. AP moves along T-tubule - 2. Voltage change is sensed by the dihydropyridine receptor (DHP), which is physically connected to the SR in skeletal muscle - 3. Is communicated to the ryanodine receptor which opens (VACR) - 4. Calcium pumped out to stimulate contraction. Contraction occurs  - 5. Calcium is pumped back into the SR. Calcium binds to calsequestrin to facilitate storage - 6. Contraction is terminated Lecture Notes 9/16 Cardiac Muscle Actin and myosin filaments Low resistance intercalated disks connect fibers Fibers are grown and intertwined Skeletal muscle aligned linear Cardiac muscle is organized into sheets Higher pressure in top contracts blood into the bottom Valve from top into bottom Pump, squeeze and twist Atria pumps top down, ventricles go down up with a squeeze and twist Non-oxygenated blood from body pumped into right atrium, then pumped into right ventricle via the tricuspid valve, then pumped to the lungs via the pulmonary valve and artery, then pumped back into the left atrium, then into the left ventricle thanks to the mitral valve, then into the body via the aortic valve into the aorta Atria is the top part, ventricles are bottom  - Sodium channels open, sodium rushes in, potassium channels open, calcium channels open and rush in, more potassium rushes in, returns back to resting - If you opened a potassium gate at resting potential, it would not rush out because inside of cell is negative and does not want to leave against charge gradient, even if concentration gradient is that way - Depolarization: Sodium channels open, allowing sodium ions to flow into the cell. - Repolarization: Potassium channels open, allowing potassium ions to flow out of the cell. This returns the membrane potential to negative. - Absolute Refractory Period - Recovery period after action - During this time the cardiac muscle cannot be re-excited - Lasts 0.25-0.30 seconds in ventricles (longer) - Takes longer to re-excite - Last 0.15 seconds in 0.15 seconds in atria (shorter) - Can re-excite faster - Absolute refractory period of cardiac muscle is near peak when potassium and calcium channels open - Relative refractory period is on the downswing, can be excited here - Excitation-Contraction Coupling - Calcium2+ Induced Calcium2+ Release (CICR) - 1. APs spread to the inside of the muscle fiber along T tubules - 2. APs trigger Ca2+ release from SR - 3. Ca2+ is released from T tubules - 4. The sliding of actin/myosin causes cardiac muscle contraction - 5. After the influx of Ca2+ ends; Ca2+ is continuously pumped back into a sarcoplasmic reticulum and extracellular space - 6. Mucopolysaccharides in tubules bind Ca2+ for storage - 7. Contraction ends  - Atrial tissue has shorter refractory period → contracts faster - Cardiac Cycle - Systole - muscle is stimulated by AP and is contracting - Diastole - reestablishing the resting Na+/K+/Ca2+ gradient and recuperating - EKG/ECG - P - atrial wave - Atrial contracting → depolarization - QRS - ventricular wave - Atrial tissue repolarizing - tiny - Ventricular depolarization - T - ventricular repolarization - Larger muscle - Valves prevent back/blow  - - Aortic Pressure Curve - Aortic pressure starts increasing during systole, after the aortic valve opens - Aortic pressure decrease toward the end of the ejection phase - Aortic pressure decreases slowly during the diastole because of the elasticity of the aorta - Blood flows into right atrium, then into right ventricle, then out and back into left atrium, then into left ventricle - Caused by pressure differences in blood between the parts and contracting, opening one way valves - Blood does not flow back into the atria - Diastole - Aortic valve closed: isovolumic relaxation - A-V valves open: rapid inflow - Diastasis - slow flow into ventricle - Atrial systole - adds some extra blood - Systole - While A-V valves closed (until P ventricle > P atria) isovolumic contraction  - Ejection phase; begins when SL valves open, when pressure threshold is reached - Aortic valve closes; isovolumic relaxation begins Lecture Notes 9/19 P wave occurs before atrial contraction QRS occurs prior to onset of ventricular contraction Electrical signal spike first → then contraction Ejection Fraction End diastolic in left ventricle volume ~ 120 mL mmHG End systolic volume ~ 50 mL Ejection volume (stroke volume) ~ 70 mL Ejection fraction = 70/120 ~ 58% (~normal) If heart rate is 70 beats/min cardiac output is: cardiac output = HR x stroke volume = 70 beats/min x 70 mL = 490 mL/min = 0.49 L/min = ~ 5 L/min If heart rate faster → pump less blood per pump If heart rate slower → more more blood per pump Around 5 L Work Output of the Heart  - Sympathetic Nerve and Parasympathetic Nerve - Sympathetic nerve accentuates the speed of your heart - Parasympathetic nerve decreases the speed of your heart - Sympathetic stimulation has systolic end around 30 mL and starts around 120 mL - Heart rate increases and pumps out at higher stroke volume ~ 90 mL - Preload and Afterload - - Preload is the pre-loading of more blood volume - Starting diastolic around 140 mL and ends systolic around 40 mL - Stroke volume around 100 mL - Afterload is bad - Heart not emptying enough - Starting diastolic around 140 mL and ends systolic around 90 mL - Stroke volume around 50 mL - Heart needs to beat faster to pump blood - Sinus (SA) node - Specialized cardiac muscle connected to atrial muscle - Located in the superior posterolateral wall of RA - Above superior vena cava as a point - Acts as pacemaker (self excitation) - RMP -55 to -60mV with inactivated fast Na+ channels - AP threshold at ~-45 mV - Internodal Pathways - SA node to the AV node  - AV node is located behind the tricuspid valve - Delays cardiac impulse - Decreased gap junction - Most delay is in AV node - SA to AV node ~0.03 s - AV node delay ~0.10 s - AV bundle delay - Purkinje System - Fibers lead from AV node into ventricles - Fast conduction; many gap junctions - AV Bundle of His travels through ventricular septum - Divides into left and right Bundle of His - Transmission time between AV bundles and last of ventricular fibers is ~0.06s - Healthy cardiac tissue discharge rates - SA node ~75/min - AV node ~50/min (escape rhythm) - Purkinje ~25/min (escape rhythm) - Left ventricular wall is thicker than right ventricular wall - Both much thicker than atria - Sympathetic Effects on Heart Rate - Sympathetic nerves release norepinephrine - As you increase your depolarization narrows - Parasympathetic Effects on Heart Rate - Parasympathetic nerves to SA and AV nodes releases Ach increasing K+ permeability Lecture Notes 9/23 Mi - Sympathetic Effects on Heart Rate - Sympathetic nerves release NE - Speeds up self-excitation - Increases SA node discharge rate, rate of conduction of impulse, and the force of contraction in atria and ventricles - Sympathetic nerve faster, heart rate up - More sympathetic blue peaks than black ones - Parasympathetic Effects - Parasympathetic nerves to SA and AV nodes releases Ach, increasing K+ permeability - Parasympathetic nerve fires faster, heart rate slows down - Na+ permeable on way up, K+ permeable on way down - Less parasympathetic blue peaks than black ones - ECG - Neuronal excitation of the muscle, then afterwards muscle contraction - P wave precedes atrial contraction - QRS complex precedes ventricular contraction - Atrial repolarization wave isn’t seen on ECG because it is obscured by QRS wave - PQ interval: time between the beginning of atrial contraction and the beginning of ventricular contraction - Exact same amount of blood in left and right ventricles - Recording of the skin surface potentials generated by electrical current resulting from spread of the cardiac impulse to surrounding tissue - Einthoven’s Law - Knowing the potentials of 2 of the 3 bipolar leads, implies that the third can be calculated by summing the first two - Lead refers to measurement points on arms and left leg - Example: - RA (Right Arm) at -0.2 mV - LA (Left Arm) at 0.3 mV - LL (Left Leg) at 1 mV - LI + LIII = LII - Lead I: (RA-LA) = -0.5 mV - Lead II: (RA-LL)= -1.2 mV - Lead III: (LA-LL) = -0.7 mV - Lead I is positive - Lead II is isoelectric - Lead III is negative - -30 degree orientation is heart vector - Height of R wave - Highest R wave in the direction that measures the heart - Vector in opposite direction would measure 0 mV  - Nicest ECG - Looking at heart from 3 orientations Lecture Notes 9/25 - Precordial Lead ECG - 3 primary lead system is useful for looking at electrical activity in vertical plane but - Precordial leads (12) are useful for looking at electrical activity in orthogonal transverse plane - Relative lengths - Using PEAK of QRS complex - If negative measurement, would go other way - Trigonometry fields - Will be given 3 leads and you need 2 - 1 is extraneous - Projections of vectors - P wave is positive in all three limbs - Depolarization begins in the right atrium - P wave is long lasting compared to QRS - Can’t be seen because of QRS complex - Draw perpendicular lines, see where they intersect  - Draw at 90 degrees from each lead and see where intersect - Then eyeball and estimate angle degrees - - You can pick the ones with the highest deflection from the baseline - Left Axis Deviation —---------------------> - Shifts counterclockwise - Changes in position - Expiration - Lying down - Excess abdominal fat - LV hypertrophy - Hypertension - Aortic valve stenosis - Aortic valve regurgitation - Congenital conditions  - Right Axis Deviation - Shifts clockwise - RV hypertrophy - Pulmonary hypertension - Pulmonary valve stenosis - Congenital conditions (VSD) - Bundle Branch Block, Axis Deviation - Axis deviation due to left branch block - Delay on the heart beating - Beats in different direction in heart - QRS complex widens If orthogonal: - - Just one moment in time - Orthogonal does not necessarily mean there's no activity, just that there's no activity at that precise moment in time - Chapter 13: Cardiac Arrhythmias - Abnormal rhythmicity of the pacemaker - Shift of pacemaker from sinus (SA) node - Blocks at different points in the transmission of the cardiac impulse - Abnormal pathways of transmission in the heart - Spontaneous generation of abnormal impulses from any part of the heart - Abnormal Sinus Rhythm - Tachycardia means a fast heart rate (>100 bpm) - Increased body temperature - Sympathetic stimulation - Toxic conditions of the heart - Bradycardia means a slow heart rate ( HBO2 - Normal blood has around 0.3 mL O2/100 mL blood  - 1.34 mL O2/gm Hb - Normal: 15 gm Hb/100 mL blood transports ~ 20 mL O2/100 mL blood - Anemic (decreased RBC): 10 gm Hb/100 mL blood transports ~ 13 mL O2/100 mL blood - Diffusion of Oxygen at the Tissue - - Diffusion of oxygen from blood to mitochondria - There is a continuous gradient of PO2 from blood to mitochondria - Oxygen is not diffused in arteries or aorta - Arteries only transport to the capillaries - Capillaries are smaller, thin arteries - Diffusion occurs at capillaries - Hemoglobin Dissociation Curve I - Comparison of the oxygen saturation curve for hemoglobin and myoglobin - Myoglobin attracts oxygen more strongly than hemoglobin - Makes sense since hemoglobin needs to attract and release - a means arterial - Hemoglobin Dissociation Curves II - - Temperature and O2 saturation (left) - Temp is colder in lungs since inspired air ~22 deg C and internal temp 37.5 (left) - pH and O2 saturation, Bohr effect (right) - CO2 and O2 saturation curve - When O2 highest in lungs, hemoglobin more likely to grab O2 - When O2 in skeletal muscle, hemoglobin more likely to release O2 - We ideally want hemoglobin to suck O2 out of the air and hold onto it until we need to release it in skeletal muscles far away → periphery - Dumping as much as possible in periphery - Transport of Carbon Dioxide - Dissolved in blood - About 20x more soluble than O2 - Venous blood: 2.7 mL/100 mL blood - Arterial blood: 2.4 mL/100 mL blood - Delta transported (arterial - venous) → 0.3 mL/100 mL blood; 7% in blood - Transport of carbon dioxide in blood - A lot of CO2 breaks down into carbonate and acid (HCO3- and H+) - Buffer - Reactions are reversed in lungs - More CO2 relatively transported but mostly buffered and released in lungs Lecture Notes 11/4 - Ventilation/Perfusion - Movement of O2/CO2 in and out and amount of blood flowing through lungs - 5 L/min blood - Relationship between adequate flow and adequate ventilation - About 4 L/min O2 - Defined as V(gas)/Q(Blood) → V/Q = (~4 L/min) / (~5 L/min) = 0.8 - If there is no diffusion impairment then the PO2 and PCO2 between an alveolus and end capillary blood are usually the same - - - V/Q = 0 (approaching 0) - Approaching venous blood conditions - Left part diagram of graph above - Venous blood - PO2 = 40 - PCO2 = 45 - V/Q = infinity (approaching infinity) - Approaching atmospheric conditions  - Right part of graph above - Atmospheric relationship - PO2 = 160 - PCO2 = 0 - Shunt: blood flow without ventilation - Dead space: airflow without blood flow - Regulation of Respiration - Sensors gather information - Central controller integrates signals - Effectors muscles (respiratory center) - - Lung Receptors - Stretch receptors - Inhibit inhalation - Hering-Breuer reflex - Irritant receptors - Bronchoconstriction - Increased ventilation - Chemical Control of Respiration - Location of sensors - Carbon dioxide - Central - Hydrogen ions - Central - Oxygen - Peripheral and central - Find voice box, look on both sides of neck - - Glossopharyngeal IX - Respiratory Center - - Effect of transections of the brain stem on respiratory patterns - Spinal cord on bottom - Big part is medulla IX-XII - Top is pons at V-VIII - DRG dorsal respiratory group - VRG ventral respiratory group - PRG pontine respiratory group (does not matter) - Most of the respiratory activity happens in the medulla in ventral  - - Chemosensitive Area of a Respiratory Center - Inside the brain stem - Medullary zone - Relation between blood and CSF pH - - Arterial blood outside the blood-brain barrier - CO2 can move across BBB - Acid, ions cannot - Chemoreceptors are very sensitive to H+ - H+ cannot cross blood brain barrier without channel  - - Peripheral Chemoreceptors - Carotid body-bifurcation - Responds to oxygen (PO2 < 100 mmHg) - Responds to carbon dioxide and H+ - Response of the carotid receptors - - As pH goes up, the number of actions potentials per unit time goes up - Brain equates CO2 to H+ → both trigger higher breathing - Left: interaction of PaCO2, PaO2, and pH - At lower pH ~ 7.15 the brain is at maximum activity - Saying it desperately needs to breathe, almost flat - Right: At normal PaCO2 and pH, O2 sensing is not important until PaO2 falls below 60 mmHg - Breathe based on CO2 generation - Control of Respiration - Changes in arterial PCO2 have greater effect than changes in arterial pH  - - PCO2 and PO2 - Hypoxic increase in ventilation inhibited by fall in PCO2 - - Walking up a hill - Hypoxic = low oxygen - As PCO2 falls, still not breathing that hard even though O2 very low - Breathing regulated by CO2 - Hypoxic increase in ventilation enhanced when PCO2 held constant - - Breathing is much more regulated by CO2 than O2 - Unless low on PCO2 - Chemical Control of Breathing (this is the one) - - Control of ventilation by peripheral chemoreceptors  - - Brain diagram: Draw pons, medulla, cerebellum, anything involved in processes - End of Exam Material Office Hours Meeting Question 1: forgot the vagal efferents Question 2a: the diaphragm contracts, and as it does the internal organs are pushed downwards and slightly out as the diaphragm expands. Then, during expiration, the abdominals contract, which shortens them, which pushes inwards on those organs and forces them back up. This is what causes the diaphragm to return to its normal position for both passive and active expiration. To show this, I needed to draw a side view of the process that shows the abdominals (which are in front of the organs) pushing into the body where the organs are, and forcing the organs to move up. Also, the chest wall was missing for my answer about passive expiration. Since it is more rigid than the lungs, it is mostly the elastic properties of the chest wall that allow for passive expiration. The lung is not involved. Question 2b: The answer I gave was wrong, as the capillaries do not vasodilate during sympathetic modulation but vasoconstrict. I was actually thinking of the bronchioles, which come from the trachea and bronchi, that vasodilate during sympathetic modulation to allow more air to come in and out. For the second part, it is true that gravity is responsible for the closing of those capillaries, but it is the effect that gravity has on pressure that is the real answer. That diagram shows that because there is less flow at the top, as you expire, some of those capillaries collapse due to the big pressure change in them. The ones at the bottom have more flow and will not collapse. Question 3a: the vagus nerve innervates only the SA node of the heart, and therefore the parasympathetic system affects only heart rate. It does not affect vasodilation or resistance or any other factor. It is modulation of the sympathetic system that does this. Sympathetic stimulation will increase heart rate, total peripheral resistance, vasoconstriction, blood pressure, decrease digestion, decrease urination, dilate bronchioles. Sympathetic decrease will do the opposite. But sympathetic stimulation going down is not the same as parasympathetic stimulation going up. They only share their effect on heart rate. Post-Exam 2: Lecture Notes 11/11 - Organization of the Nervous System - Sensory division (inputs): tactile, visual, auditory, olfactory - Sensors - Integrative division (processing/decisions): process information, creation of memory - Controls - Motor division (outputs): respond to and move about in our environment - Plants - - - Spinal cord - More than just a conduit for signals from periphery of body to brain and vice versa - Spinal cord contains:  - Walking circuits - Withdrawal circuits - Support against gravity circuits - Circuits for reflex control of organ function - Higher Brain or Cortical Level - - Cortext never functions alone, always in association with lower centers - Large memory storehouse - Each portion of the nervous system performs specific functions, but it is the entire cortex that opens the world up for one’s mind - Cross Section of the Brain - - Gray matter has a lot of neuronal cell bodies - White matter has a lot of neuron processes (axons) - Corpus callosum is the connection between left and right brain - Anatomy of a Neuron - Dendrite input, axon output - Soma is the cell body - - - 3 major components: - Soma - main body of the neuron - Axon - extends from the soma to the terminal, the effector part of the neuron - Dendrite - projections from the soma, the sensory portion of the neuron - Inputs come from top - Communication Between Neurons - Through release of neurotransmitters; >50 compounds have been identified as transmitter substances - Neuronal communication is one-way conduction, only transmits signals from an axon to a dendrite, or the stimulated tissue (i.e. skeletal muscle) - Neurotransmitters communicate an action from one spot to another - Neurotransmitters - Acetylcholine (ACh) - Parasympathetic - Norepinephrine (NE) - Sympathetic - Epinephrine (E) - Serotonin - Happy sauce - Glutamate - General excitatory neurotransmitter in brain  - Polarizes - Gamma-aminobutyric acid (GABA) - General inhibitory - Hyperpolarizes - The Synapse - Presynaptic vesicles, contain neurotransmitters, substances to excite or inhibit postsynaptic neuron - An action potential causes emptying of a small number of vesicles into the synaptic cleft which excites or inhibits the postsynaptic neuron - - - Mechanism of Neurotransmitter Release - Presynaptic membranes contain voltage-gated Ca2+ channels - Depolarization of the presynaptic membrane, by an action potential, opens Ca2+ channels - Influx of Ca2+ induces the fusion of synaptic vesicles to the membrane and release of neurotransmitter by exocytosis - Neurotransmitters - Neurotransmitters are chemical substances that function as synaptic transmitters - Small molecules, act as rapidly acting transmitters  - Excitatory: glutamate, acetylcholine, norepinephrine, dopamine - Inhibitory: GABA, glycine, dopamine - Neuropeptides, more potent than small molecule transmitters and cause more prolonged actions: endorphins, enkephalins, VIP - Hypothalamic releasing hormones: TRH, LHRH - Pituitary peptides: ACTH, prolactin, vasopressin - Action of Neurotransmitter on Postsynaptic Neuron - Postsynaptic membrane contains receptor proteins for the transmitter released from the presynaptic terminal - These receptors contain a neurotransmitter binding component and an ionophore component (either opens an ion channel or activates a second messenger system) - Neurotransmitter changes function of ion channel on postsynaptic neuron - By changing the ion channels - Changes resting membrane potential (depolarizes or hyperpolarized) - If sum of neurotransmitters is sufficient, we get an action potential - Second Messenger Activities - Cause prolonged changes in the activity of neurons (seconds to months) - Goes longer - Some processes like memory require long term changes in neuronal activity and function - About 75% of SMAs are transduced with G-protein coupled receptors - G-protein initiates a cascade of events that leads to an increase in cAMP which causes protein phosphorylation which leads to alterations in the cellular activity - Primarily gets sodium channels open - Lecture Notes 11/14 - Neurotransmitters - Neurotransmitters are chemical substances that function as synaptic transmitters - Calcium rushing in causes depolarization - Small molecules: act as rapidly acting transmitters - Excitatory: glutamate, acetylcholine, norepinephrine, dopamine - Inhibitory: GABA, glycine, dopamine  - Neuropeptides: more potent than small molecule transmitters and cause more prolonged actions - Endorphins, enkephalins, VIP - Hypothalamic releasing hormones: TRH, LHRH - Pituitary peptides: ACTH, prolactin, vasopressin - Excitatory synapse involve Na+ rushing into cell membrane from synapse - Glutamate - Depolarizes the postsynaptic neuron - Inhibitory synapse involve Cl- rushing into cell membrane from synapse - GABA - Hyperpolarizes the postsynaptic neuron - - Action of Neurotransmitter on Postsynaptic Neuron - Postsynaptic membrane contains receptor proteins for the transmitter released from the presynaptic terminal - These receptors contain a neurotransmitter binding component and an ionophore component (either opens an ion channel or activates a second messenger system) - The difference of you opening the door vs telling someone to tell someone to tell someone to open the door - Direct vs second messenger - Second Messenger Activators - Cause prolonged changes in the activity of neurons (seconds to months) - Some processes like memory require long term changes in neuronal activity and function  - About 75% of SMA are transduced with G-protein coupled receptors - G-proteins activation initiates a cascade of events that leads to an increase in cAMP which causes protein phosphorylation which leads to alterations in the cellular activity - Postsynaptic Potentials - Excitatory Postsynaptic Potential (EPSP) - Na+ ions rush to inside of membrane, neutralizing part of the negativity of the resting membrane potential - Relative increase in voltage, above the normal resting potential (to a less negative value ~5 mV - - Inhibitory Postsynaptic Potential (IPSP) - Inhibitory synapses open K+ (K+ diffuses out) or Cl- channels (Cl- moves in) causing a relative membrane hyperpolarization - Increase in negativity beyond the normal resting membrane potential level - not cones - - - Spatial Summation of Postsynaptic Potentials - Spatial summation - Excitation of a single presynaptic neuron on a dendrite almost never induces an action potential - Each terminal on the dendrite accounts for about a 0.5-1.0 mVV EPSP - When multiple terminals are excited simultaneously, the EPSP may exceed the threshold and induce an action potential - Must show action potential spike - EPSPs and IPSPs constant magnitudes  - EPSP and IPSP should have same amplitude but different signs - If EPSP and IPSP happen at same moment in time, they cancel out - Neurons always firing at some nominal rate - Hillock is where decision is made about action potential happening or not - Threshold is either met or not - Spatial summation assumes that each neuron is equidistant from the hillock and therefore their waves reach hillock at same time - These waves sum up - If amplitude of summed wave is sufficient, action potential happens - See chart on left - Temporal Summation of Postsynaptic Potentials - Temporal summation - A neurotransmitter opens a membrane channel for ~1 msec, the postsynaptic potential lasts for ~12 msec - A second opening of the same membrane channel can increase the postsynaptic potential to a greater level. Therefore, the more rapid the rate of terminal stimulation the greater the postsynaptic potential - Rapidly repeating firings of a small number of terminals can summate to reach the threshold for action potential firing - Sum each of them at literally each msec and draw the combined curve - They sum, but not at the same moment in time - If more time between them, they will not build as high - Like twitch muscles summing action potentials - Overall - “FIGURE 3.6.2 Hypothetical scheme illustrating spatial and temporal summations. Consider a motor neuron with four inputs. Inputs A, B, and C are excitatory inputs that produce EPSPs when excited, and D is an inhibitory input that produces an IPSP. Firing of A, B, or C alone results in EPSPs that are subthreshold. Simultaneous firing of A, B, and C summates to produce a suprathreshold potential that produces an action potential in the motor neuron. Simultaneous firing of A, B, C, and D is below threshold because the IPSP of connection D lowers the postsynaptic potential. This is spatial summation. Even though firing of A is insufficient to reach threshold, repetitive firing of A can summate to produce suprathreshold postsynaptic potentials. Summation of the postsynaptic potentials in time is temporal summation.” - Firing faster → long term firing frequency up - Firing slower → long term firing frequency down - When inhibitory action potential reaches dendrite, it signals for vesicles to diffuse across membrane and return a certain amplitude - Not Cones - Function of Dendrites in Stimulating Neurons - Dendrites are spaced in all directions from the neuronal soma. This allows signal reception from a large spatial volume providing the opportunity for summation of signals from many presynaptic neurons  - Dendrites do not transmit action potentials - Transmit waves from IPSPs and EPSPs - Have few voltage gated Na+ channels - Dendrites transmit signals by electrotonic conduction - Transmission of current by conduction in the fluids of the dendrites - No generation of action potentials in the dendrites - Special Characteristics of Synaptic Transmission - Synaptic fatigue - Overuse - Rapid stimulation until stores of transmitter in presynaptic terminals decrease → reduction of postsynaptic discharge - Fatigue is a protective mechanism against excess neuronal activity - Like fatigue from working out - Post-tetanic facilitation - Enhanced responsiveness following repetitive stimulation - Results from a build-up of Ca2+ ions in the presynaptic terminals resulting in more vesicular release of transmitter - Types of Sensory Receptors - Mechanoreceptors - Detect deformation - Thermoreceptors - Detect change in temperature - Nociceptors - Detect damage (pain receptors) - Electromagnetic - Detect light - Chemoreceptors - Tase, smell, CO2, O2, etc - Sensation and Excitation - Each of the principle types of sensation: touch, pain, sight, sound, is called a modality of sensation - Each receptor is responsive to one type of stimulus energy. Specificity is a key property of a receptor - How the sensation is perceived is determined by the characteristics of the receptor and the central connections of the axon connected to the receptor - Mechanical deformation which stretches the membrane and opens ion channels - Application of chemicals which also opens ion channels - Change in temperature which alters the permeability of the membrane - Electromagnetic radiation that changes the membrane characteristics  - Receptor Potential and Excitation - The membrane potential of the receptor, the greater the intensity of the stimulus, the greater the receptor potential, and the greater the rate of action potential generation - Lecture Notes 11/25 - Postsynaptic Potentials - Excitatory postsynaptic potential (EPSP) - Na+ ions ruhs to inside of membrane, neutralizing part of the negativity of the resting membrane potential - Inhibitory postsynaptic potential (IPSP) - Inhibitory synapses open K+ (K+ diffuses out) or Cl- channels (Cl- moves in), causing a relative membrane hyperpolarization - Increase in negativity beyond the normal resting membrane potential level - - Spatial Summation of Postsynaptic Potentials - Spatial summation  - Excitation of a single presynaptic neuron on a dendrite almost never induces an action potential - Each terminal on the dendrite accounts for about a 0.5-1.0 mV EPSP - When multiple terminals are excited simultaneously, the EPSP may exceed the threshold, and induce an action potential - 1. Simultaneous stimulation by several presynaptic neurons - 2. EPSPs spread from several synapses to axon hillock - 3. Postsynaptic neuron firing - - Temporal Summation - A neurotransmitter opens a membrane channel for ~1 msec, the postsynaptic potential lasts for ~12 msec - A second opening of the same membrane channels can increase the postsynaptic potential to a greater level. Therefore, the more rapid the rate of terminal stimulation the greater the postsynaptic potential - Rapidly repeating firings of a small number of terminals can summate to reach the threshold for firing - 1. High frequency stimulation by one presynaptic neuron - 2. EPSPs spread from one synapse to axon hillock - 3. Postsynaptic neuron fires - Slide skipped? - Special Characteristics of Synaptic Transmission - Synaptic fatigue - Rapid stimulation until stores of transmitter in synaptic terminals decrease → reduction of postsynaptic discharge - Fatigue is a protective mechanism against excess neuronal activity - Overworking the neurons - Post-tetanic facilitation - Enhanced responsiveness following repetitive stimulation - Results from a build up of Ca2+ ions in the presynaptic terminals resulting in more vesicular release of transmitter - Memory recall from a pattern of nerve excitation - Types of Sensory Receptors - Mechanoreceptors - Detect deformation - Thermoreceptors - Detect change in temperature - Nociceptors - Detect pain (pain receptors) - Electromagnetic - Detect light - Chemoreceptors - Taste, smell, CO2, O2, etc - Starts in dorsal root ganglion and transmits signals all throughout body via axons - Sensation and Excitation - Each of the principle types of sensation: touch, pain, sight, sound, is called a modality of sensation - Each receptor is responsive to one type of stimulus energy. Specificity is a key property of a receptor - How the sensation is perceived is determined by the characteristics of the receptor and the central connections of the axon connected to the receptor - Mechanical deformation which stretches the membrane and opens ion channels - Applications of chemicals which also opens ion channels - Change in temperature which alters the permeability of the membrane - Electromagnetic radiation that changes the membrane characteristics - Receptor Potential and Excitation - The membrane potential of the receptor, the greater the intensity of the stimulus, the greater the receptor potential, and the greater the rate of action potential generation - In this example, greater depolarization results in greater action potential generation - There is a limit - Receptor Adaptation to Stimuli - When a continuous stimulus is applied, receptors respond rapidly at first, but response declines until all receptors stop firing - Rate of adaptation varies with type of receptor - Therefore, receptors respond when a change is taking place (i.e. think of the feel of clothing on your skin) - Differentiators - - Transmission of Receptor Information to the Brain (afferent inputs) - The larger the nerve fiber diameter the faster the rate of transmission of the signal - Velocity of transmission can be as fast as 120 m/s or as slow as 0.5 m/s - Nerve fiber classification - Type A - myelinated fibers of varying sizes, generally fast transmission speed - Type C - unmyelinated fibers, small with a slow transmission speed - Larger diameter, bigger velocity - - The somatosensory cortex - Somatic Sensory Cortex II  - Located in the postcentral gyrus - Highly organized with distinct spatial orientation - Each side of the cortex receives information from the opposite side of the body - Unequal representation of the body - Lips have the greatest area of representation followed by the face and the thumb - Trunk and lower body have the lowest represented area - Cortical homunculus - - Cellular Organization of the Cortex - Cortex is outer layer -  - Layers I and II receive diffuse inputs from lower brain centers - Layer III project axons to closely related volumes of the cortex, presumably for communicating between similar areas - Layer IV receives incoming axons that spread both up and down - Layer V and VI project axons to more distant parts of the central nervous system - Layer V to the brainstem and spinal cord - Layer VI to the thalamus - Lecture Notes 12/2 - Chapter 4.2 Somatic Sensation and Pain - Classification of Somatic Sensations - Mechanoreceptive - stimulated by mechanical displacement - Tactile - Touch - Pressure - Vibration - Tickle and itch - Position or proprioceptive - Static position - Rate of change - Thermoreceptive - Detect heat and cold - Nociceptive - Detect pain and are activated by any factor that damages tissue - Some endings are deeper or shallower - Free nerve endings are closest to skin surface - Tactile Receptors (describe 2 for the final) - Free nerve endings  - Detect touch, pressure, itch - Pain, heat, cold - Found everywhere in the skin and other tissues - Meissner’s corpuscles - Rapidly adapting (within a fraction of a second) and detect movement of light objects over skin - Found on nonhairy (glabrous) skin, fingertips and lips - Merkel’s discs - Respond rapidly at first and then slowly adapt, detect steady state - Found on hairy and glabrous skin - Hair end organ - Adapts rapidly and detects movement over the body - Ruffini’s end organ - Slowly adapting and respond to continual deformation of skin and joint rotation - Pacinian corpuscle - Detects vibration and other rapid changes in the skin very rapidly adapting and is stimulated only by rapid movement - The Dorsal Column System - Almost all sensory info enters the spinal cord through the dorsal roots of the spinal nerves - Myelinated goes through spinal cord, switches side half way through - High degree of spatial orientation - Larger myelinated fibers - Anterolateral System - Smaller unmyelinated fibers ~0.5-40m/s (also some myelinated) - Low degree of spatial orientation, transmits a broad spectrum of modalities: pain, thermal sensations, crude touch and pressure, tickle and itch, sexual sensations - Come in and immediately switch sides - Pain sensations (unmyelinated) - Somatic Sensations: Pain, Headache, Thermal Sensations - Pain - Occurs whenever tissue is being damaged - Protective mechanism for the body - Should cause the individual to remove painful stimulus - Two types of pain: fast pain and slow pain - Fast pain felt within 0.1 sec of the stimulus and is sharp in character - Slow pain begins after 1 second or more and is throbbing or aching in nature - Pain receptors and stimulation - All pain receptors are free nerve endings and can be stimulated by: - Mechanical (stretch) - Thermal - Chemical(s) - Bradykinin, histamine, potassium ions, acids, and proteolytic enzymes - Prostaglandins and substance P enhance the sensitivity of pain endings, but do not directly excite them - Pain receptors do not adapt to the stimulus - Extracts from damaged tissue cause pain when injected subcutaneously - Bradykinin causes the most pain, and may be the most responsible biochemical agent for causing the tissue damage type of pain - Local increase in K+ concentration can contribute to pain - Dual Pain Pathways I - Fast pain fibers are transmitted in the neospinothalamic tract (velocity ~6-30 m/s) (neo = new) - Slow pain fibers are transmitted in the paleospinothalamic tract (velocity ~0.5-2 m/s) (paleo = old) - Neospinothalamic Tract - New + spine + thalamus - Fast-sharp pain that can be localized well; however, fast pain fibers must be stimulated with other tactile receptors for the pain to be highly localized - 1st order(?): on entering the cord, pain fibers may travel up or down 1-3 segments and terminate on neurons in the dorsal horn - 2nd order neuron crosses immediately to the opposite side and passes to the brain in the anterolateral columns - 3rd order neurons go to the cortex - Paleospinothalamic Tract - There is poor localization of slow pain, often to just the affected limb or part of the body - Most associated neurons do not project to the somatosensory cortex - Pain pathways  - - The Appreciation of Pain - Removal of the somatic sensory areas of the cortex does not remove the ability to perceive pain - Pain impulses to lower areas can cause conscious perception of pain - Therefore cortex probably important for determining the quality of pain - Analgesia System of the Brain and Spinal Cord - The brain/CNS has the capability to suppress pain fibers - Neurons can activate a pain inhibitory complex in the spinal cord - Periaqueductal gray area neurons send axons to the nucleus raphe magnus and the nucleus paragigantocellularis (not important) - Raphe magnus and the nucleus paragigantocellularis neurons send axons to the dorsal horns of the cord (not important) - EXAM: Enkephalin is believed to cause both pre- and postsynaptic inhibition where they synapse in the dorsal horns - Most popular neurotransmitter that is released in the CNS that is anti-pain  - - Endogenous Opiate Systems - Injection of a minute quantities of morphine into the third ventricle of the brain produces a profound and prolonged analgesia - Started the search for morphine receptors in the brain - Several opiate-like substances have been identified - Choroid plexus produces cerebrospinal fluid (CSF)? - Enkephalin, enkephalin, enkephalin is the opiate of choice - Function of the Opiate System - Pain suppression during times of stress - Important part of an organism’s response to an emergency is a reduction in the responsiveness to pain - Effective in defense, predation, dominance, and adaptation to environmental challenges - Headaches Skipped - Migraines prolonged vasodilation - Hangover irritation of the meninges by alcohol breakdown products and additives - Spasms and tension, sinus headache Lecture Notes 12/5 - Referred Pain from the Viscera - Potential causes of visceral pain: ischemia, chemical irritation, muscle spasm, over distension - Pain from an internal organ that is perceived to originate from a distant area of the skin - Mechanism is thought to be intermingling of second order neurons from the skin and the viscera - Viscera have few sensory fibers except for pain fibers - Highly localized damage to an organ may result in little pain, widespread damage can lead to severe pain - Headache Pain - Brain tissue itself is insensitive to pain - Pain sensitive structures of the brain are the membranes that cover the brain and the blood vessels - Dura - Blood vessels of the dura - Venous sinuses - Middle meningeal artery - Intracranial headache - Meningitis - Inflammation of the meninges resulting in a severe headache - Migraine - Results from abnormal vascular phenomenon - Vasospasm followed by prolonged vasodilation - Vasodilation causes stretching of the coverings of the blood vessels - Hangover - Irritation of the meninges by alcohol breakdown products and additives - Extracranial headache - Muscular spasm tension headache - Emotional tension may cause tension of muscles attached to the neck and scalp which causes irritation of scalp coverings - Sinus headache - Irritation of nasal structures - Eye strain - Excessive contraction of the ciliary muscle in an attempt to focus, contraction of facial muscles - Thermal Sensations - Throughout the body, there are many more cold receptors than warm receptors - Density of cold receptors varies - Highest on the lips, lowest on the trunk - Freezing cold and burning hot are the same sensation because of stimulation of pain receptors  - - Stimulation of Thermal Receptors - Cold receptors respond from 7 to 44 C with the peak response at 25 C - Warm receptors respond from 30 to 44 C with the peak response at 44 C - Relative degree of stimulation of the receptors determines the temperature sensation - Thermal receptors adapt to the stimulus but not completely - END OF BME 311 CONTENT Final Exam Review: - Vasomotor Center vs Respiratory Center - Autonomic system does not cover breathing - Diagram of pons and medulla from front and side - Side to show vasomotor and respiratory centers - Action Potential Threshold for Summations - IPSP/EPSP is about 12-15 ms for the change in potential  - After threshold reached, action potential spike up to Nernst potential and then back down to resting potential - On way up, sodium channels are open (more permeable to sodium) - On way down, potassium channels are open (more permeable to potassium) - - For cardiac myocytes, calcium channels makes it look different - - Transduction Cascade - Action potential down axon, calcium rushes in, neurotransmitter sent out into the synaptic cleft - IPSP - About 12-15 ms  - - For both IPSP and EPSP, a little bit of a faster rise than a return - - Axon Hillock Signals for Spatial and Temporal Summation - - If you excite all at the same time, you get spatial summation - If you excite them at different moments in time, temporal summation - Signals are received and summed at hillock - IPSPs and EPSPs have same magnitudes - Paleospinothalamic Tract - Up through brain stem, into thalamus, and out - Free nerve endings are the oldest pain fibers  - Paleo and neo pathways - Some cross right away and some go up and cross - Block diagram with respiratory center - Hypoxia when not enough oxygen comes in or not enough oxygen in environment - Ex. climbing tall mountains - You will start to breathe more - Breathe more CO2 out - Blood becomes more basic - CO2 is down, need to breathe less - O2 is down, need to breathe more - Not a very big change in breathing - Breathing is more regulated by CO2 - Too much CO2, drive to breathe increases to get CO2 out - Chemoreceptors Block Diagram - We get air from outside - Chemoreceptors in aortic arch and carotid sinuses - VMC has nothing to do with breathing - - VMC is not supposed to be here? - Excite respiratory center? 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