Exam Two

1. Describe the flow of depolarization through the conducting pathway, particularly noting how the depolarization starts in the SA node, is slowed at the AV node and then is rapidly transmitted throughout the ventricles by the Purkinje fibers.

Electrical activity travels from the SA node very quickly to the AV node where it slows down and then travels a small distance to the bundle of HIS and goes down the septum and travels to the left or right throughout the ventricles of the heart through the purkinje fibers quickly

Draw and label a diagram that shows skeletal muscle at all anatomical levels. Illustrate the structural characteristics of whole muscle (intact muscles attached to the skeleton), single muscle cells, myofibrils and sarcomeres. At the sarcomere level your drawing should identify the molecular components that are the basis of its striated appearance. Include two different stages of myofilament overlap.

Know this! diagram in notes

3. List the factors that determine the tension developed in a whole muscle and explain how each contributes to the amount of tension generated.

Motor unit size: i. Precise movements (small amounts of force)--> small motor units ii. Large-scale and powerful movements--> large motor units Motor unit recruitment: i. The process of increasing the number of active motor units ii. Recruitment--> responsible for smooth movements rather than jerky movements iii. Different motor units of an entire muscle are not stimulated to contract in unison 1. Some may be contracting while others are relaxed--> asynchronous recruitment a. Delays muscle fatigue and allows for contraction to be held for long periods

1. List the factors that determine the tension developed in a whole muscle and explain how this is controlled.

Motor unit size: i. Precise movements (small amounts of force) small motor units ii. Large-scale and powerful movements large motor units iii. This is controlled within the body, there are different motor unit sizes depending on how much tension is required Motor unit recruitment: i. The process of increasing the number of active motor units ii. Recruitment responsible for smooth movements rather than jerky movements iii. Different motor units of an entire muscle are not stimulated to contract in unison 1. Some may be contracting while others are relaxed asynchronous recruitment a. Delays muscle fatigue and allows for contraction to be held for long periods iv. This was controlled by changing the amplitude of the electrical stimulus acting on the motor point.

How do the musculoskeletal pump, the respiratory pump, gravity, increases in preload and the venous valves contribute to venous return?

Musculoskeletal pump: • Veins has valves and the veins are surrounded by muscle • When you go on your tippy toes you "push" blood through the veins back towards the right heart • The muscle squeezes and the creates a pressure to push the blood out of the vein • What if the valves don't work properly? • Varicosity or varicose veins • The valves couldn't close properly • Due to change in body size (bigger bodies)

How do the musculoskeletal pump, the respiratory pump, gravity, increases in preload and the venous valves contribute to venous return?

Respiratory pump: • Further pushing of the blood to the right heart by the diaphragm • All you need to do in inhale to push the blood back to the right heart. • The diaphragm in the picture is relaxed, when it contracts it pushes blood to the right heart • Big blue line is the vena cava

3. Describe the relationship between blood velocity and total cross-sectional area. Why is blood flow the slowest in the capillaries of any location in the vasculature?

See notes for graph • Capillaries have the largest total cross-sectional area • Things slow down at the level of the capillaries--> this is because capillaries are used for exchange in the organs/muscles

4. Describe the parts (receptor, sensory neuron, integrator, motor neuron, effector=target) of the baroreceptor reflex arc.

a. 7 parts i. Stimulus--> increased BP ii. Receptor--> baroreceptor (sensor) detects pressure change iii. Sensory neuron--> afferents iv. Integrator--> Cardiovascular control center (in the medulla/brain stem) v. Motor neurons--> efferents vi. Effector (target)--> heart (SA node and AV node, heart muscle/myocardium) and the vasculature (decrease in SNS--> decrease in NE and alpha receptors) 1. Decrease in Sympathetic (NE) 2. Increase in Parasympathetic (ACh) vii. Response--> decrease in BP

7. Name three (3) roles of ATP in skeletal muscle contraction and relaxation.

a. ATP is used by the myosin head to energize and orient it b. ATP binding to myosin head to detach it from actin after the power stroke c. ATP is used by the Ca-ATPase to pump Ca ions out of the sarcoplasm

3. Explain how a baroreceptor works i.e. what makes it depolarize, where it sends information to, what are the consequences of that information.

a. Baroreceptors are specialized tissues that detect change in pressure; sensors in pressure b. Carotid--> Special set of baroreceptors that go toward the head c. Aortic--> special set of baroreceptors that go toward the rest of the body (systemic) d. Baroreceptor completely surrounds itself around the artery (carotid or aortic for example)

4. Compare and contrast the electrical activity of skeletal and cardiac muscle cells. Consider the duration and ionic basis of the skeletal and cardiac action potentials, and the functional consequences of their differences.

a. ECC is different between muscle types b. Skeletal: DHPR is just a voltage sensor; mechanically couples action potentials to Ca2+ release from the SR c. Cardiac: DHPR is a voltage gated Ca2+ channel; 20% of calcium is from ECF and 80% is from the SR; CICR--> calcium induced calcium release d. Smooth: most calcium from ECF

8. Describe how smooth muscle activation and relaxation differ from the activation and relaxation of skeletal muscle.

Thick and thin filaments but no myofibrils: i. Thick filaments have myosin crossbridges along their entire length (no bare zone at the center) ii. Thin filaments composed of actin and tropomyosin but no troponin iii. Thin filaments are bound to membrane anchored protein assembles Smooth muscle activation: i. Calcium binds to calmodulin in the cytoplasm ii. Ca2+-calmodulin complex binds to and activates myosin light chain kinase (MLCK) iii. Activated MLCK phosphorylates the myosin regulatory light chain (RLC) by transferring a phosphate from ATP iv. Phosphorylated myosin heads bind to actin and begin contraction by crossbridge cycling

2. Describe the three layers of vessels (connective tissue for strength and elastance), smooth muscle for regulating of the radius size and endothelium for a smooth lining) and apply characteristics of the layers to the function of a given vessel. For example the aorta has mostly connective tissue, helping it to stretch and spring back during the cardiac cycle. This connective tissue also helps the aorta withstand the high pressure, high velocity blood flow exiting the left ventricle. Repeat this thought process for arterioles, capillaries and veins.

~3 major layers of the vasculature: i. Endothelial cells (inside) ii. Structures that connect the cells together--> basement membrane and elastic connective tissue iii. Smooth muscle ~ see notes for the graph ~Arteries: high pressure, high velocity ~Arterioles: high resistance--> controlling blood flow, distribution, highly innervated by SNS ~Capillaries: slow flow(low pressure), thin walled ~Venuoles: collection of blood (deoxygenated ~Veins: lowest pressure, highest capacitance ( most of the blood here) 2/3

2. Discuss the mechanical and electrical events of the cardiac cycle during diastole and systole from the Cardiac Cycle Diagram. Not only should student follow each graph, sounds, ECG, volume curve, pressure curve, etc. they should also be able to move up and down the diagram from curve to curve. For example, after the P wave, one should see an increase in atrial pressure as a result of atrial contraction. This diagram will be provided on the exam. Don't memorize it; learn how to work through it.

(see Notes for diagram labeled) Four events: 1. Electrical ----i. QRS=ventricular depolarization 2. Mechanical ----i. Ventricular contraction 3. Pressure change ----i. LVP=left ventricular pressure ----ii. AP=aortic pressure 4. Volume/valve ----i. Valves: left AV loses, aortic valve opens 2. Blood leaves ventricle: stroke(?) volume

6. Define a motor unit and describe the order of recruitment of motor units during skeletal muscle contractions producing low, moderate and high amounts of tension.

-A motor unit: a motor neuron and the population of muscle fibers it innervates -Recruit more motor units for more strenuous tasks -Recruit smaller or less motor units for less strenuous tasks -Goes from low to moderate to high with less motor units to more motor units -Motor Unit one: slow oxidative i. Small diameter muscle fibers ii. Few fibers per motor unit iii. Generates least tension -Motor unite 2: fast oxidative i. Midsized muscle fibers ii. Moderate # of fibers per motor unit iii. Generates moderate tension -Motor unit 3: fast glycolytic i. Large muscle fibers ii. Many fibers per motor unit iii. Generates most tension quickly

4. List the steps in excitation-contraction coupling in skeletal muscle, and describe the roles of the sarcolemma, transverse tubules, sarcoplasmic reticulum and the thin and thick filaments. Be certain to include the roles of modulatory proteins such as troponin and tropomyosin and of calcium ions.

-An action potential travels along the sarcolemma, plasma membrane of the muscle fiber, through the T tubules, which are thousands of invaginations in the sarcolemma. This allows the action potential to spread quickly and to all parts of the muscle fiber at essentially the same instant -This action potential into the T tubules causes the release of Ca2+ from the SR into the sarcoplasm and muscle contraction then begins. -EC occurs at the triads of the skeletal muscle fiber which consists of a transverse tubule and two opposing terminal cisternae of the SR ---T tubule and terminal cisternae are mechanically linked together by two groups of integral membrane proteins: dihydropyridine receptor (DHP receptor) and Ca2+ release channels or ryanodine receptors ------Dihydropyridine receptor (DHP receptor) ---------L-type (long lasting) voltage gated calcium channel--> Main role in EC coupling is to serve as voltage sensors that trigger the opening of the Ca2+ release ------Found in the T-tubule membrane ------Moves in response to action potentials ---Ryanodine receptor (RyR) ------Calcium release channel ------Found in the SR membrane ------Opens to release Ca2+ when the DHP receptor moves -When the action potential reaches the T tubule, the DHP receptors detect the change in voltage and undergo a conformational change that ultimately causes the Ca2+ release channels to open -Once these channels open, Large amounts of Ca2+ flow out of the SR in to the sarcoplasm around the thick and thin filaments -These released calcium ions then binds to troponin which then undergoes a conformational change that causes tropomyosin to move away from the myosin binding sites on actin. -Once these binding sites are free, myosin heads bind to them to form crossbridges and the contraction cycle begins

5. Describe the properties of the withdrawal reflex initiated by stepping on a sharp object.

-Causes flexion of a limb in order to withdraw the limb from a painful stimulus -Steps: i. Stepping on a tack stimulates the dendrites of a pain sensitive neuron ii. This sensory neuron then generates action potentials, which propagate into the spinal cord iii. Within the spinal cord (integrating center), the sensory neuron activates interneurons that extend to several spinal cord segments iv. The interneurons activate motor neurons in several spinal cord segments. As a result, the motor neurons generate action potentials, which propagate toward the axon terminals v. ACh released by the motor neurons causes the flexor muscles in the thigh (effector) to contract, producing withdrawal of the leg. This reflex is portective because contraction of flexor muscles moves a limb away from the source of a possibly damaging stimulus. A comparable reflex occurs with painful stimulation of either upper limb

9. List the potential sources of calcium that contribute to smooth muscle activation.

-Extracellular Ca 2+ can enter the cell down its huge gradient (10,000 times higher concentration outside the cell than inside) via: i. VG calcium ion channels ii. Ligand gated calcium ion channels iii. Stretch activated cation (Na+ and Ca 2+) -Release of calcium ions from intracellular stores (SR) i. G-protein coupled receptors -Smooth muscle contractile proteins i. Troponin: no! role as calcium sensor is replaced by calmodulin ii. Calmodulin: calcium sensor in smooth muscle--> Ca 2+ bound calmoduin complex binds to myosin light-chain kinase, thereby activatin the kinase iii. Tropomyosin: yes. Howevery, without troponin to loc its position it cannot block myosin's binding to actin as strongly as it does in skeletal muscle iv. Actin: yes! Still provides the cable for myosin to pull along v. Myosin: must be phosphorylated by the action of myosin light-chain kinase to be able to bind to actin and start cross bridge cycling vi. Myosin light chain kinase: activated by Ca+2 -calmodulin, phosphorylates myosin's regulatory light chain when active vii. Myosin light chain phosphatase: dephosphorylates myosin's regulatory light chain to relax smooth muscle

4. Describe the role of the gamma efferent system and explain the significance of alpha-gamma co-activation.

-Gamma motor neurons from CNS innervate intrafusal fibers controlling the contraction of these fibers within the muscle spindle -Excitation of gamma motor neurons and alpha motor neurons at the same time -Contraction of the spindle ends lengthens the central region of the spindle and maintains stretch on the sensory nerve endings (446) -Maintains spindle function when muscle contracts -Alpha motor neurons innervate extrafusal fibers, gamma motor neurons innervate intrafusal fibers

3. Describe the series of events initiated by striking the patellar tendon with a percussion hammer that leads to extension of the lower leg (i.e. the knee jerk reflex)

-Involves extension of the leg at the knee joint by contraction of the quadriceps femoris muscle of the thigh in response to tapping the patellar ligament -Steps: i. Slight stretching of a muscle stimulates sensory receptors in the muscle called muscle spindles which monitor the length of the muscle ii. In response to being stretched, a muscle spindle generates a receptor potential. If the receptor potential reaches threshold, it triggers one or more action potentials that propagate along a somatic sensory neuron through the dorsal root of the spinal nerve and into the spinal cord iii. In the spinal cord (integrating center), the sensory neuron makes an excitatory synapse with and thereby activates a motor neuron in the ventral gray horn iv. If the excitation is strong enough, one or more action potentials arise in the motor neuron and propagate along its axon, which extends from the spinal cord into the ventral root, and through peripheral nerves to the stimulated muscle. The axon terminals of the motor neuron form neuromuscular junctions with skeletal muscle fibers of the stretched muscle v. ACh released by action potentials at the NMJs triggers one or more action potentials in the stretched muscle (effector), and the muscle contracts. Thus, muscle stretch is followed by muscle contraction, which relieves the stretching

2. Compare and contrast the structure, anatomical location, and function of muscle spindles and Golgi tendon organs.

-Muscle spindles: i. Structure: consists of a connective tissue capsule that surrounds several sensory nerve endings wrapped around 3-10 intrafusal muscle fibers ii. Anatomical location: within muscles iii. Function: STRETCH REFLEX monitor the length of the muscle (both static muscle length and changes in muscle length)--> Slight stretching of a muscle stimulates muscle spindles -Golgi tendon organs: i. Structure: consists of a connective tissue capsule that surrounds one or more sensory nerve endings entwined around bundles of collagen fibers within the tendon ii. Anatomical location: lie within a tendon near its junction with a muscle iii. Function: TENDON REFLEX; detect and respond to changes in muscle tension that are caused by passive stretch or muscular contraction less sensitive than the stretch reflex -Both feedback systems send information to the brain and these are usually protective

Draw the structure of the neuromuscular junction including important proteins that are found on the pre- and post-synaptic membranes (label these proteins and other structural features).

-Pre-synaptic terminal i. Neuronal axon terminal ii. Has VG calcium channels -Motor end plate i. Muscle membrane ii. Has nicotinic receptors (always ion channels) iii. On either side of the end plate, there are Na VG channels iv. Acetycholinesterase is there to help break down acetycholine or get rid of it -End plate potential (EPP) i. Depolarization generated at the muscle membrane due to binding of the neurotransmitter ACh-->When ACh binds, it opens and allows Na to come in and K to leak out ii. Triggers an action potential if the EPP exceeds the threshold for VG sodium channels

4. List the energy sources for muscle contraction and rank the sources with respect to their relative speed and capacity to supply ATP for contraction.

Creatine Kinase: i. Really fast because it is one step reaction ii. Transfers phosphate from Creatine-phosphate to ADP to regenerate ATP iii. Creatine phosphate is a "storehouse" of high energy phosphate which is accumulated during rest in muscle cells iv. Creatine Kinase provides ATP during first few seconds of a contraction v. The ATP production is rapid, ut limited by the amount of CP stored in cell vi. Powers very short periods of muscle activity ---1. Happens first to allow time for multistep energy sources to kick in Glycolysis: i. Multistep reaction ---1. Takes a little bit more time ii. Anaerobic: can produce ATP from glucose in the absence of O2 iii. Converts 1 glucose to 2 ATP iv. Kicks in during high intensity exercise v. In the presence of large amounts of glucose, can produce large quantities of ATP vi. Glucose can come from blood or from breakdown of muscle glycogen vii. Powers short periods of muscle activity viii. Muscle building is involved in this ix. Type two muscles or fast twitch muscles Oxidative Phosphorylation: i. Multistep reaction ii. Requires oxygen and mitochondria ---1. Phosphorylation of ADP occurs in mitochondria iii. Converts 1 glucose to 36 ATP iv. Converts fatty acids to ATP v. Converts amino acids to ATP vi. Multi-enzyme pathway that requires O2 initially (first 5-10 minutes of activity), glycogen is the major fuel vii. Next 30 minutes, blood borne glucose and fatty acids contribute fuel, eventually giving way to mostly fatty acids viii. Power extended periods of muscle activity ix. Muscles are not bulky, they are slim because they have optimized the level of the oxidation in the muscles they already have x. Type one muscle or slow twitch muscles xi. Slow

4. Discuss the deflections (as electricity is flowing through the heart) and isoelectric events (when the heart is totally depolarized or repolarized) of the ECG. Specifically discuss what electrical event is occurring during the P wave, the QRS complex and the T wave.

Depolarization event: • Deflection makes an upward curve when there is a positive current and the depolarization is going from the negative to the positive lead • Deflection makes a downward curve when there is a negative current and the depolarization is still going from the negative to the positive lead Repolarization event: • Deflection makes a downward or negative curve when there is a positive current and the repolarization goes from the positive lead to the negative lead • Deflection makes an upward or positive curve when there is a negative current and the repolarization goes from the positive lead to the negative lead Flat ECG or no deflection: • Isoelectric event: Current is still moving but is moving perpendicular to the lead P wave—depolarization of atria- activity of the SA node (pacemaker): • Atrial contraction; systole; "kick" QRS complex—depolarization of ventricles: • S1 sound or "lub" sound occurs at the QRS complex and this is when the ventricles contract and the AV valves are closing--> very quick response • Mechanically--> Ventricular contraction; systole • Obscures the atrial repolarization that occurs around the same time as the QRS complex T-wave—repolarization of ventricles: • S2 sound or "dub" sound occurs at the T wave and this is when pulmonary and aortic valves close • Ventricular repolarization; diastole

3. Explain the scientific basis for ECG measurement. In your answer, address the ability of the body to conduct electricity and the placement of the recording electrodes. Students are not held responsible for knowing the lead configurations of all 12 leads but rather understanding how any given lead (two recording electrodes and a ground electrode) is used to detect the ECG.

ECG only records electrical activity Lead: composed of 3 electrodes; one negative, one positive, and one that's a ground or reference electrode • Detects electrical activity of the heart--> positive and negative electrode connect to form a lead. • Ground--> is used as a reference meaning that • Detecting the current flow--> the depolarization and repolarization of the heart membrane--> represented as deflections (line moving along with time) • Leads don't move • Having different leads provides different viewpoints of the electrical activity going through the heart Heart: top is base and bottom is apex • First lead in heart is placed at the top towards the base of the heart ---• Negative on left side and positive on right side and moves from negative to positive ---• Will produce a smaller ECG form than lead 2 ---• Electrical activity is moving away from the heart • Second lead runs along right side of heart parallel with the MVA ---• Negative more superior to the positive electrode and goes from negative to positive ---• Most common and produces largest ECG of the three ---• Provides most parallel electrical activity moving along the heart • Third lead runs relatively perpendicular to the MVA of heart on the left side ---• Negative more superior to the positive electrode and moves from positive to negative electrode ---• Will produce a slightly smaller ECG form than lead 2 ---• Provides a waveform that is most perpendicular to the heart

2. List the factors that determine the tension developed by single muscle fibers and explain the molecular basis for each factor.

Frequency of stimulation: i. Refractory period: period of lost excitability when a fiber responds to the first stimulus but not to the second one that occurred immediately after the other. ii. Wave summation: phenomenon in which stimuli arriving at different times cause contractions with greater tension ---1. A second stimulus occurring after the refractory period but before the muscle fiber has relaxed produces a stronger second contraction iii. If a fiber is stimulated at a higher rate, it can relax only slightly between stimuli ---1. Unfused (incomplete) tetanus: The result is as sustained but wavering contraction iv. If a fiber is stimulated at an even higher rate and it does not relax at all ---1. Fused (complete) tetanus: the results is a smooth, sustained contraction in which individual twitches cannot be detected and maximum tension is reached. v. Wave and tetanus occur when additional Ca ions are released from the SR by subsequent stimuli while the levels of Ca ions in the sarcoplasm are still elevated from the first stimulus; peak tension is 5-10 times greater than peak tension by a single twitch Muscle fiber length: i. Length-tension relationship explained above Muscle fiber diameter: i. Thicker diameter--> more myofibrils--> generate more tension ii. Think a bodybuilder can lift more than a thin person

5. Diagram the chemical and mechanical steps in the cross-bridge cycle, and explain how the cross-bridge cycle results in shortening of the muscle.

Involves 4 major steps 1. ATP hydrolysis--> Myosin head hydrolyzes ATP and becomes energized and oriented 2. Attachment of myosin to actin--> Myosin head binds to actin, forming a crossbridge 3. Power stroke--> Myosin crossbridge pivots, pulling the thin filament past the thick filament toward center of the sarcomere 4. Detachment of myosin from actin--> As myosin head binds ATP, the crossbridge detaches from actin

3. Compare and contrast isometric and isotonic muscle contractions with respect to the duration of the latent period, the velocity of contraction and the circumstances under which each type of contraction will take place.

Isometric contractions i. This will take place when the muscle does not change in length and the tension generated is not enough to exceed the load ii. Latent period: iii. Velocity: 0, there is no movement Isotonic contractions i. This will take place when the muscle changes in length and the tension developed by the muscle remains almost constant ii. Velocity of concentric contraction: load and velocity are inversely related ---1. If the load is zero, the velocity is at its maximum ---2. If the load increases, the velocity decreases ---3. If the load is equal to or exceeds the maximum tetanic tension that the muscle can produce, the velocity of shortening is zero and the contraction becomes isometric -First, it's isometric because when the calcium starts to bind its going to generate force which is during the latent period, and then after the tension overcomes the load is when isotonic begins because that when the movements occurs or the muscle changes in length (what isotonic is)

1. Describe the relationship between different degrees of myofilament overlap and the shape of the length-tension relationship.

Length-tension relationship indicates how the forcefulness of muscle contraction depends on the length of the sarcomeres within a muscle fiber before contraction begins i. 2.0-2.4um (close to the resting length in most muscles), the zone of overlap in each sarcomere is optimal, and the muscle fiber can develop maximum tension ii. If the sarcomeres are stretched to a longer length, the zone of overlap shortens and fewer myosin heads can make contact with thin filaments tension the fiber can produce decreases. ---1. Get too tangled and cannot optimally contract iii. If sarcomeres are stretched to 170% of its optimal length, there is no overlap between thick and thin filaments therefore the myosin heads cannot bind to thin filaments and the muscle cannot contract and tension is zero. iv. If the sarcomere length becomes under-stretched, the tension that can develop again decreases. This is because the thick filaments crumple as they are compressed by the z discs resulting in fewer myosin heads making contact with thin filaments

5. Explain why in lead II, the QRS and T wave are both in the upward (positive) deflection. As part of this objective, students should consider the refractory periods of the myocytes at the base and the apex of the heart.

Mean ventricular axis (MVA) most electrical activity goes towards the apex: • In tall people, with a long torso, the apex of the heart is facing more towards the ground because it is more affected by gravity • In shorter people, their heart is not as affected by gravity than in tall people so it is more towards the left (the apex) • In pregnant women, the heart is even more towards the left due to a change in body shape Electrical activity from the SA node has tendency to go the right so the other side counteracts and goes to the left; Lead II is positioned most parallel to the mean ventricular axis • ??? Why does the T wave have upward deflection? • T wave is ventricular repolarization followed by ventricular relaxation • There is always current-repolarization has current ---• Two negatives make a positive so the current and the repolarization=positive deflection • Depolarization has + current

1. Describe how the structure of a capillary enables capillary exchange.

See lecture video for class 18 and notes

5. Construct a table of structural, enzymatic, and functional features of fast-glycolytic, fast oxidative, and slow-oxidative fiber types from skeletal muscle.

Slow oxidative: i. Red muscle, small diameter cells ii. Slow myosin aerobic metabolism iii. Mostly oxidative phosphorylation iv. Many mitochondria and capillaries v. Large amounts of myoglobin to aid in O2 diffusion and to store O2 vi. Resistant to fatigue vii. E.g. postural muscles Fast oxidative: i. Red muscle, intermediate diameter cells ii. Fast myosin, aerobic and anaerobic metabolism iii. Mostly phosphorylation which requires O2 iv. Many mitochondria v. Moderately likely to fatigue Fast glycolytic: i. White muscle, large diameter cells ii. Anaerobic metabolism iii. Fast myosin ATPase so tension development is fast iv. Mostly glycolytic metabolism v. Large amounts of glycogen to provide fuel for glycolysis vi. Fewer capillaries and mitochondria vii. Small amounts of myoglobin (white meat) viii. Greatest amount of tension ix. Prone to fatigue

2. Distinguish between a single twitch and a tetanic contraction in skeletal muscle and explain why twitch response is smaller in amplitude than a tetanic contraction.

Twitch: brief contraction of a group of muscle fibers within a muscle in response to a single action potential --3 sequential phases: 1. the latent period: brief delay (2 msec) that occurs between application of the stimulus and the beginning of contraction; during this time, excitation-contraction coupling is occurring 2. the contraction period: (10-100 msec) during this, ca ions bind to troponin, myosin binding sites on actin are exposed, and myosin cross bridges are formed; peak tension develops 3. the relaxation period: (10-100 msec) Ca ions are actively transported bac into the SR, myosin binding sites are covered by tropomyosin, myosin heads detach from actin, and tension in the muscle fiber decreases Tetanic: a sustained muscle contraction evoked when the motor nerve that innervates a skeletal muscle emits action potentials at a very high rate.

5. Explain how the length of the refractory period prevents tetany in cardiac cells. (HINT: Think about skeletal muscle. The short action potential and long twitch creates a situation where skeletal tetany can occur. What happens to the action potentials in cardiac tissue that prevents tetany in cardiac tissue?)

a. In cardiac muscle, when the AP is at the plateau phase it is in absolute refractory period which means it cannot undergo tetany because then all of the valves would be open or contracting b. It occurs because VG Na channels that are initially activated during the depolarizing phase of the AP quickly become inactivated and must wait until the membrane repolarizes and returns to the resting state before they are capable of being activated again. c. Refractory period is 20-200 msec d. The refractory period is long in cardiac muscle fibers due to the prolonged plateau phase of the action potential. Because the duration of the refractory period lasts almost as long as the duration of contraction (300msec), the cardiac muscle fiber cannot be re-excited until its previous contraction is almost over. Therefore, summation of contraction and tetanus do not occur in cardiac muscle e. If there is tetanus in the heart, it would not be able to function as a pump because it would not have a chance to relax and refill with blood

7. Describe the function of higher centers in motor control.

a. Intention to move, etc. b. Integration of sensory feedback c. Sensory, motor, and association cortex

1. Describe function of intercalated discs. Specifically, discuss how gap junctions electrically connect cardiac myocytes and desmosomes physically connect cardiac myocytes. Discuss why this facilitates the myocardium working as a pump (functional syncytium = many cells working as one unit).

a. Intercalated discs: allow for the flow of calcium to go through the heart from the SA node into the myocytes to the AV node to the purkinge ---Connect cardiac myocytes ---Desmosomes: responsible for the transmission of FORCE or tension ---Gap junctions: transmit electrical activity with calcium ions ---Together these transmit information between cells in a function syncytium ---Functional syncytium--> work together as one unit ------Good because the heart has to contract and relax at the same time

6. List the regions of the brain involved in middle level of motor control and describe the main function that these structures serve.

a. Motor programs to coordinate movements based on intention, sensory feedback, etc. b. Include basal nuclei, thalamus, cerebellum, motor centers in brain stem

4. Contrast the duration of a muscle action potential with the duration of a muscle contraction, and explain the significance of this difference.

a. Muscle action potential travels along the axis fairly quickly, whereas a muscle contraction can last a long time, especially with isometric contractions when one needs to hold something in place.

3. Compare/contrast the action potentials and properties of the typical ventricular cardiac myocyte vs. the SA nodal cells. Discuss membrane potential stability/instability at rest. Compare the voltage gated channel (Na+, Ca2+ and K+) permeability to membrane potentials changes (depolarization, plateau and repolarization) during a typical cardiac myocyte AP and the SA node AP.

a. Nodal cells are found in the sinoatrial node or the atrioventricular node b. Purkinge fibers: allows for the spread of electrical activity c. Flow of depolarization goes from the SA node to the AV node to the Purkinge d. Pacemaker cells: autorhythmic meaning that they generate their own action potentials; signal for contraction, smaller and fewer contractile fibers, and do not have organized sarcomeres e. SA node generates the heart rate f. Pacemaker action potential is unstable--> SA node and AV node ---i. The resting membrane potential is unstable due to "funny" channel or IF ---ii. Funny channel--> both Na and K ions can go into the channel ---iii. If there is an increase in sodium in these channels, it's going to activate the VG calcium ion channel which is depolarization (calcium is responsible for the depolarization) ---iv. After it peaks out, there is going to be a repolarization that is done by VG K channels g. Cardiac action potential (see notes to see what it looks like) last about 300 ms h. Cardiac action potentials: purkinje, endo and epi ventricle ---i. Depolarization goes from the endo to the epi (inside to outside)--> this means that there are contractions starting on the inside of the heart going to the outside of the heart next ---ii. Repolarization goes from epi to endo (outside to inside)--> relaxation starts on outside and goes to the inside i. Pacemaker action potentials: SAN (sinoatrial node) and AVN (atrioventricular node)

7. What is the mechanism of fatigue? Don't know but...

a. Not absence of ATP - or else there would be rigor b. High EC K concentration c. Lactic acid—disproven d. Build-up of ADP - inhibition of crossbridge cycling e. Disruption of calcium regulation, possibly by malfunctioning Ca ion channels on the SR

6. Describe Ca2+ accumulation in the sarcoplasmic reticulum mediated by Ca2+-ATPase. Explain the role that these (Ca2+-ATPase pump proteins) transporters play in muscle function.

a. Release of calcium is for muscle contraction--> It travels into the sarcoplasm and binds to the thin filaments in the sarcomere b. Ca ATPase starts working right when Ca starts being released and pumps Ca from the sarcoplasm into the SR c. Calcium ions flow into the sarcoplasm more rapidly than they are transported back into the SR by the pumps. d. After last action potential has propagated throughout the T tubules, the Ca release channels close. e. As the pumps continue to work, the concentration of calcium ions in the sarcoplasm quickly decreases. f. Inside the SR, molecules of a calcium-binding protein called calsequestrin bind to the Ca2+, enabling even more Ca2+ to be stored or sequestered within the SR and the concentration is then 10,000 times higher in the SR than in the sarcoplasm g. As Ca level in sarcoplasm drops, Ca dissociates from troponin, tropomyosin covers myosin-binding sites on actin, and the muscle fiber relaxes.

5. Which is faster? Rise of twitch or fall of twitch?

a. Rise of twitch is faster because the concentration of calcium in the SR is super high and the fall is slower because Ca ATPase pump is working against that gradient to bring the Calcium ions back in.

2. Give an overview of the function of the organelles (T-tubules, sarcoplasmic reticulum, contractile apparatus) and proteins (voltage-gated Ca2+ channels and SR calcium release channels) that are responsible for excitation-contraction coupling in cardiac muscle (i.e. calcium induced calcium release). Remember that you have encountered some of these proteins in neurons and skeletal muscle cells. Build on your previous knowledge.

a. SR: contains 80% of the calcium needed for excitation contraction coupling b. Mitochondrion: source of ATP; heart has a lot c. T-tubules: are large and branch; come from the sarcolemma; connect to the SR d. Thick and thin filaments: contractile apparatus; they cross bridge after actin hydrolyzes ATP and binds to the myosin e. AP cruises along the sarcolemma and eventually hits something--> hits the dihydropyridine receptor its gonna cause calcium to come into the cell from the ECF--> when calcium comes into the cell through the DHPR, its gonna hit the RYR (ryanodine receptor) and bind to it--> this opens the L-type voltage-gated Ca channels in the T-tubule membrane and allows calcium to flow into the sarcoplasm--> the entering calcium functions as trigger calcium that binds to Ca release channels in the SR--> this causes channel in the SR to open and release of calcium from the SR--> going to find its way to the sarcomere and bind to the troponin on the actin filament--> this causes the cross bridge to happen and a shortening of sarcomeres (contraction)--> now its time to relax so the sarcomere has to shorten--> calcium comes off of actin and some of it goes back into the SR through the Ca ATPase pump and some of it goes out of the cell through the sarcolemma via sodium calcium exchanger--> calcium goes out through this and sodium comes in--> sodium is also being pumped out and K pumped in via the sodium potassium pump (REMEMBER there are leak channels too! f. Cardiac muscle contraction can be graded ---i. Force generated is proportional to # of active crossbridges--> determined by calcium bound to troponin--> cardiac myocyte can vary force generated--> what determines contractility of the heart ---ii. Length of the sarcomere affects force of contraction--> preload is basically the amount of volume in the heart--> frank-starling law of the heart

List in sequence the steps involved in neuromuscular transmission for skeletal muscle and point out the location of each step on a diagram of the neuromuscular junction; name the neurotransmitter and describe three ways the neurotransmitter molecules in the synaptic cleft are removed after the nerve stops sending signals.

a. When an action potential occurs in a somatic motor neuron, it releases ACh molecules stored in the synaptic vesicles of the synaptic end bulbs. b. ACh then diffuses across the synaptic cleft and binds to nicotinic ACh receptors on the motor end plate, generating a depolarizing graded potential called an end plate potential c. A single EPP is typically large enough to depolarize adjacent regions of sarcolemma to threshold, resulting in the generation of muscle action potential. d. Because the NMJ is usually near the midpoint of the muscle fiber, once the muscle action potential arises, it propagates through the muscle fiber membrane in both directions away from the NMJ toward the ends of the fiber. e. As the muscle action potential passes through the membrane (sarcolemma and T tubules) it triggers a chain of events that ultimately leads to contraction of the muscle fiber f. Thus a single action potential in a somatic motor neuron elicits a single action potential in a skeletal muscle fiber, which in turn causes the skeletal muscle fiber to contract. g. Once nerve action potentials in the somatic motor neuron cease, ACh is no longer released h. Three ways ACh is removed from the synaptic cleft: Reuptake; Diffusion; Acectycholinesterase, an enzyme, breaks down any ACh that is present in the synaptic cleft

4. Calculate mean arterial pressure (diastolic + 1/3 (systolic-diastolic)) & describe BP measurement using a blood pressure cuff. Students should know this formula.

b. High pressure: systolic (110 mm Hg in the picture) Low end: diastolic pressure (about 70 mm Hg in the picture) c. Pulse pressure (SP-DP) is 40 mm Hg ----i. 110-70= 40 mm Hg d. Mean arterial pressure= PP/3 + DP ----i. 40/3 + 70 = 83 mmHg

9. Define afterload and discuss situations in which a high afterload could decrease the stroke volume. The opening and closing of the semilunar valves should factor into your answer. Specifically students should understand that the left ventricle is more muscular than the right ventricle because the left ventricle pumps against 5 times the afterload as compared to the right ventricle.

~Afterload: pressure required to eject blood from ventricles to aorta or pulmonary artery i. Systolic blood pressure ii. The combination of EDV and Arterial resistance during ventricular contraction and ventricular wall tension ~How hard do ventricles have to work to open the pulmonary or aortic valves i. Depends on pressure from pulmonary artery or aorta ----1. 80 mmHG in left ventricle ----2. 20 mmHG in right ventricle ~Hypertension: i. What if afterload increased? ii. What if the ventricles can't contract, what happens to SV? ~Frank-Starling Law of the Heart i. Within limits, increased Venous return stretches the heart muscle and results in a larger SV ii. Stretch adjusts sarcomeres to an optimal length (length tension curve) iii. "the more you fill, the more forceful the ejection" ~Why is this good? i. Prevents backups ii. Heart keeps up with VR ----1. VR=CO

6. Describe role of arterioles in blood distribution since we don't have enough blood to send to every body part all the time. In other words, how do the arterioles make sure that blood goes where it is needed? Be able to give examples of local factors that regulate blood flow.

~Arteriole are basically the resistance vessels i. Control of blood flow, "fine tuning",--> is due to smooth muscle (most of all the vessels)--> can control smooth muscle through innervation and the smooth muscle in the arterioles are highly innervated (SNS) ~Arterioles control the distribution of blood (specifically CO) i. At rest: ----1. Brain--> 10-15% C.O. ----2. Kidney--> 20% C.O. (kidneys filtering blood, making urine) ---3. Muscle--> 15-20% C.O. ii. Heavy exercise: ----1. Brain--> 5% CO ----2. Kidney--> 1% CO ----3. Muscle--> 80-90% CO ~"Small arteries"

4. Explain how each of the Starling's forces (capillary hydrostatic, capillary protein osmotic, interstitial hydrostatic, interstitial protein osmotic) contributes to capillary filtration and flow into the lymphatic vessels.

~Blood flowing through arteriole into the capillary and some of the stuff comes out of the capillary • Things that come out of capillary wall is through filtration -----• Total filtration in body--> net filtration -----• Could be oxygen, could be glucose -----• Shouldn't filter out RBCs or large things ~Filtration comes from arteriole/capillaries into the lymph vessels and/or interstitial and absorption is coming from lymph vessels or interstitial into the venous system ~Starling's forces: • Bulk flow due to filtration is dependent on (two forces regulate bulk flow): -----• Hydrostatic pressure gradient--> water -----• Oncotic pressure gradient--> Protein or colloid ~Hydrostatic pressure • Fluid and gravity; blood pressure and gravity • Higher below the heart and lower above the heart • Standing person -----• Pressure towards feet is higher and lower at the head • Hydrostatic pressure influences how blood is distributed • Hydrostatic pressure varies with pressure ~Timing: reflex vs. hormone • Neural reflex: fast change in position or activity • Hormone reflex: slow; longer term effects

5. Discuss the dual innervation of the heart and the regulation of HR and SV by ANS. Both the parasympathetic and sympathetic nervous systems innervate the SA node but these two systems have opposite effects on the heart rate. Identify which neurotransmitters are released by each branch. Discuss the mechanism of this modulation of the heart rate by neurotransmitters (i.e. which channels are opened).

~Both the SA node and the AV node is controlled by the parasympathetic system via Vagus with ACh (Slow or stop) ~Both the SA node, AV node, and the heart muscle of the myocardium are controlled by the sympathetic system via norepinephrine (fast) ----i. Innervation of the heart muscle myocardium ~PNS: ACh--> funny channel--> lower freq AP--> slower heart rate ~SNS: NE--> IF channel--> higher freq. AP --> faster heart rate

6. Discuss the factors that regulate the cardiac output (CO): heart rate, preload, contractility and afterload.

~CO: amount of blood that comes out of the heart per minute (L/min) ~Stroke volume(amount of blood shooting out of aorta) x HR = CO ~The higher the HR the greater the CO

3. Calculate the CO from the product of HR and SV. Note that SV = EDV-ESV. Students should know this formula. Students should know that an average CO is 5 L/min.

~CO: amount of blood that comes out of the heart per minute (L/min)i ~HR (bpm) x Stroke volume= CO ~Stroke volume= EDV-ESV ----i. EDV is usually about 130 mL and ESV is usually about 60 mL ----ii. SV=70mL

3. Describe arterial pressure changes during the cardiac cycle and how the vascular principle of elastic recoil (also called elastance) permits the vessels (particularly the aorta) to maintain a diastolic pressure.

~Elastance: ability of vessel to return to original shape after a stretch, elastic recoil of arteries keeps the blood flowing during diastolic pressure, continuous, pulsatile blood flowb. ~Compliance (stretching part of vessel) i. Change in volume/change in pressure ii. Compliance decreases with age iii. Veins more compliant than arteries iv. The aorta is compliant during systole v. As blood goes from the ventricles into the aorta during ventricular contraction, this flow of blood out of the ventricles into the aorta is called stroke volume which expands the aorta or stretches it (compliance) ~Elastance i. Ability of vessel to return to original shape after stretch ii. Elastic recoil of the arteries keeps blood flowing during diastole iii. Converts an on/off pump to a continuous, pulsatile blood flow--> blood flow that increases during ventricular systole and decreases during ventricular diastole iv. The aorta is elastic during diastole v. As the blood moves through and out of the aorta, the aorta goes back to its original shape

1. Describe the relationship between blood flow, mean arterial pressure and vascular resistance (Ohm's Law).

~Flow (Q)= change in pressure/resistance ~Flow (Q) in mL/min, change in pressure mm Hg ~Blood flow (Q) in the cardiovascular system is: i. Directly proportional to the pressure gradient, change in P ----1. Q is proportional to change in Pressure (increase Q increase change in pressure) ii. Mean arterial pressure average blood pressure in an individual iii. Inversely proportional to the resistance, R to flow ----1. Q is inversely proportional to the R ~Causes of Pressure Changes i. Pressure created by contracting muscles is transferred to blood ii. Driving pressure/pressure gradient (change in P) is created by the ventricles iii. If blood vessels dilate: there is a decrease in resistance and blood pressure drops iv. If blood vessels constrict: there is an increase in resistance and blood pressure rises v. Changes in volume affect blood pressure such that: an increase in volume (e.g. stroke volume) increases blood pressure ~ Fluid flow through a tube depends on the pressure gradient i. Flow through a tube is proportional to the pressure gradient ii. The higher the pressure gradient, the greater the fluid flow iii. If there is no pressure gradient, there is no flow

8. Define contractility and discuss the importance of intracellular calcium to contractility.

~Force and intensity of contraction (especially at ventricles) i. Intracellular Ca2+ (sarcoplasmic reticulum) ii. # of Crossbridges (actin and myosin) ~Inotrope--> chemical that affects contractility i. Positive ----1. Increased contractility by increased [Ca2+] intracellular or Ca2+ sensitivity of troponin--> caffeine ----2. Increases SV ----3. Norepinephrine, epinephrine ii. Negative ----1. Decreased contractility ----2. Decreases SV ----3. ACh (indirect through HR) ----4. Beta blocers ----5. Ca2+ channel blockers ~SNS stimulation has a positive inotropic effect

How do the musculoskeletal pump, the respiratory pump, gravity, increases in preload and the venous valves contribute to venous return?

~Gravity: affects distribution of blood • Hydrostatic pressure: pressure and gravity • When laying on the back, blood is evenly distributed -----• Hydrostatic pressure is even -----• Effect of gravity is the same throughout the body • When standing -----• More blood pooling at the feet (high pressure) and less at the head (low pressure)

1. Discuss intrinsic (local tissue factors) and extrinsic (sympathetic nerves and hormones) regulators of arteriolar smooth muscle tone. Big picture idea is as follows: intrinsic, local factors regulate blood flow whereas extrinsic factors regulate blood pressure.

~Intrinsic: tissue removed from body--> maintain its properties i. Vasodilation: lumen is expanding because radius is expanding; increasing in CO2 or drop in O2--> trying to get rid of CO2 or trying to get more O2 to get through ii. Vasoconstriction: lumen decreases because the radius decreases; what can cause this intrinsically is a hormone that comes out of the endothelium called endothelin--> this hormone goes directly to the smooth muscle so the smooth muscle contracts to vasoconstrict the muscle ~Extrinsic: 2 things that contribute--> nerve stimulation and hormones i. Nerve stimulation ----1. SNS--> NE ii. Hormones ----1. Angiotensin II--> potent vasoconstrictor -------a. This contributes to vasoconstriction ~Vasoconstriction i. GPCR--> alpha adrenergic receptor--> INVOLVED IN VASOCONSTRICTION ii. Norepinephrine is ligand that binds to this receptor ~Vasodilation i. GPCR--> beta 2 receptor ii. Norepinephrine is ligand that binds to this receptor

5. Compare and contrast laminar (smooth and quiet) and turbulent flow (disorganized flow). Discuss how these two kinds of flow are important to determining blood pressure with a blood pressure cuff. Specifically, students should discuss principles of noninvasive measurement of the BP i.e. occlusion of the vessels with the blood pressure cuff and using Korotkoff sounds to determine diastolic and systolic pressure.

~Laminar flow: when blood flows through a blood vessel in a smooth, streamlined manner that is parallel to the vessel axis i. Fluid behaves as if it were comprised of many layers and as they move they slide past one another. ii. Layer closest to the vessel wall moves very slowly because it adheres to the wall and therefore has the greatest resistance, and each successive layer towards the center moves progressively faster because as the distance from the vessel wall increases, resistance to flow decreases. ~Turbulent flow: components of blood move at various angles to the axis of the vessel and is when blood flows through an abnormally constricted area, moves over a rough surface, makes a sharp turn, or exceeds a critical velocity i. Causes blood to mix--> forming whorls that increase the interaction between blood and the vessel wall, resulting in vibrations that are heard as sounds ii. There is more interaction between blood and the vessel wall, so there is greater resistance during turbulent flow than during laminar flow ~When the cuff is deflated enough to allow the brachial artery to partially open during systole, a spurt of blood passes through, and this spurt of blood is turbulent resulting in the first sound heard through the stethoscope. During the diastolic pressure, the laminar flow returns, and the sounds disappear. i. Turbulent flow=systolic, laminar flow=diastolic

Describe how changing vessel length, vessel radius and blood viscosity changes the vascular resistance (Poiseulle's Law). These formulae will be provided on the exam. Students should know how to use the formulae to solve pressure and flow problems.

~Poiseuille's Law ---Resistance, R=8Ln/Πr4 or R is proportional to Ln/r4 ------R=radius ------Resistance is proportional to the length of the tube (blood vessel) ------Resistance is proportional to n or the thickness of the fluid (blood) (#RBC)--> Resistance increases as viscosity increases ------R is inversely proportional to the tube radius to the fourth power (R∝(1/r4) ~If resistance increases, then flow decreases. If resistance decreases, then flow increases. ~Resistance and Flow in Blood vessels ---Small change in radius has a large effect on resistance to blood flow ---Blood flow through a vessel is inversely proportional to resistance ---Vasoconstriction causes decreased blood flow: ------Decrease in blood vessel diameter/radius ------Increase in resistance in a vessel ---Vasodilation causes increased blood flow: ------Increase in blood vessel diameter/radius ------Decrease in resistance in a vessel ~Mean arterial pressure(Change in P)= Cardiac output or CO (Q) x Total peripheral resistance (R)

7. Define preload making sure to include sarcomere length in your answer. Discuss how venous return regulates cardiac output (Frank-Starling law of the heart).

~Preload: amount of blood before ejection=EDV i. Degree of stretch on the heart ~Frank starling law of the heart i. SV increases as EDV (end diastolic volume) increases ii. EDV deterimined by venous return ----1. CO=SVxHR ---------a. SV=EDV-ESV ----2. CO=VR (what you put out depends on what you put in) ~Venous return i. From right heart to lungs to left heart ii. Determined by: ----1. Skeletal muscle pump: ----2. Respiratory pump ----3. Sympathetic innervation of veins ~Preload and sarcomere length i. Degree of stretch before contraction ii. End diastolic volume --> before systole (see notes for graph)

1. Use your knowledge of the flow of blood through the heart to explain the operation of the valves and the events of the cardiac cycle. Explain mechanism of valve opening/closing. Explain the importance of pressure gradients for valves to open and close.

~Right ventricle and left ventricle i. Pulmonary artery comes from the right ventricle, heads out, and goes towards the lungs ii. Aorta comes out of left ventricle and heads out to the body iii. Valves ----1. Tricuspid valve/right AV valve--> between right atrium and right ventricle, has three flaps when you look at it from above ----2. Mitral valve/left AV valve--> between left atrium and left ventricle, valve that goes down from left atrium to left ventricle ----3. Pulmonary valve--> Going from right ventricle and into right pulmonary artery ----4. Aortic valve--> Separates the left ventricle and the aorta ~Blood flow into the heart i. right side: blood coming from the body is blue and deoxygenated; comes from vena cava and enters into the right atrium--> then into the right ventricle fill it up and when it becomes flow--> blood ejects out into pulmonary artery into the lungs--> blood then becomes oxygenated--> comes into the left atrium through the pulmonary vein--> will go through the left AV valve and fill the left ventricle--> blood leaves left ventricle through the aortic valve and the aorta will distribute blood to the body ~how does blood move through this process? i. pressure gradients when the atria are full of blood in atrial diastole they contract--> atrial systole/kick and when they contract they are going to eject blood into the ventricles--> the ventricles are going to have less pressure because of the blood (high pressure form atria and low pressure from ventricles)--> creates a pressure gradient ii. the valves help because they ensure one way flow of blood so there isn't back flow ~All four valves can close at the same time; All four valves are never open at the same time; Only 2 sets of valves are open at any given time ~Ventricular diastole: ventricles are filling with blood, the aortic valve and pulmonary valve are closed and the AV valves are open i. During the filling of the ventricles are filling with blood, its going to cause the AV valves to close ii. Full ventricles--> all 4 valves are closed ~Ventricular systole: the muscles in the ventricles will react and develop pressure to eject the blood from the ventricles into the aorta or pulmonary; either the aortic valve or pulmonary valve will open and at this time the AV valves are closed ~Opening and closing of the valves depends on the pressure and volume in the different steps of where the blood is in the heart in the chambers at a given time

2. Relate principles of negative feedback to blood pressure regulation. Blood pressure regulation is one of the most important negative feedback mechanisms in the body.

~See LO 4 ~Hydrostatic pressure i. Fluid and gravity; blood pressure and gravity ii. Higher below the heart and lower above the heart iii. Standing person ----1. Pressure towards feet is higher and lower at the head iv. Hydrostatic pressure influences how blood is distributed v. Hydrostatic pressure varies with pressure ~Timing: reflex vs. hormone i. Neural reflex: fast change in position or activity ii. Hormone reflex: slow; longer term effects

7. Describe the venous contribution to venous return.

~Venous return --•Veins: • capacitance vessels 70% of blood stored here • lower pressure and high capacity than in arterial system -----• CO=VR • If you mobilize venous blood, you're going to increase your venous return, and therefor increase your cardiac output ~Orthostatic hypotension • Getting dizzy or passing out when getting up suddenly • Failure of the baroreceptors to respond quickly • When standing too quickly, blood pools to feet quickly • Compromise cardiac output because venous return moved toward feet • What promotes it--> age, resting blood pressure, blood volume ~Venous return must match cardiac output; All of the following things affect venous return 1. Venous pressure gradient 2. Venous valves 3. Skeletal muscle pump 4. Respiratory pump 5. Venoconstriction--> Smooth muscle lining the veins ~Venous return must equal CO • CO=SVxHR -----• SV= EDV-ESV ----------• EDV depends on preload, contractility, and afterload ----------• Afterload is dependent on the pressure or force on the other side of the valve

5. Apply the concept of Starling's forces to edema. In other words, how do changes in Starling's forces result in edema (swelling)

• Filtration far greater than absorption -----• More fluid out of capillaries--> Capillaries more permeable • Inadequate drainage so lymphatics aren't working as well

6. Explain the role of lymphatic vessels in the maintenance of the interstitial fluid compartment.

• Lymphatic vessels are used for drainage; there are too much stuff flowing through the capillaries so the excess stuff absorbs into the lymph vessels • Lymphatic system is going to return a lot of the stuff back to the venous system or venous circulation and some goes from interstitium into the venous system--> absorption • Interstitial fluid drains into lymphatics -----• ~3 oz lymph/day • Returns filtered plasma proteins to circulatory system • Filters pathogens, involved in immune response • Absorbs fats, moves to circulatory system

2. Describe the function of precapillary sphincters in the intrinsic regulation of blood flow; these structures are sensitive to surrounding tissue factors and dilate to permit blood flow into capillary beds. Give examples of local factors that affect precapillary sphincters. NOTE: these are some of the same local factors that regulate arterioles.

• Precapillary sphincters: smooth muscle cells • Local factors: • Relaxation: CO2, or lack of O2 • Constriction: metabolites, endothelin See notes and video for class 18

2. Compare and contrast AV node cells and Purkinje fibers. What are the properties that help the AV node bring about AV delay? What are the properties of the Purkinje fibers that help them spread ventricular depolarization quickly and extensively?

• There are fewer gap junctions and cells at the AV nodes because the AV node slows the electrical activity down; therefore there are a lot at the SA node • There are more gap junctions and more cells at the purkinje fibers because the activity travels quickly through these fibers