NPB101 Midterm 2

muscle functions

moves you, moves body parts, move/manipulate stuff, move stuff through you (breathing and eating)

muscle body composition

skeletal muscle

• 30% - 40% of body weight

• voluntary & striated muscle

smooth muscle

• 10% of body weight

• involuntary and striated muscle

cardiac muscle

• found only in heart

• involuntary and unstriated muscle

organization of skeletal muscle

whole muscle —> fasicle (bundle of fibers) —> muscle fibers (single cell) —> myofibril —> sacromere —> thick and thin filaments

sacromere

functional unit of muscle shortening

each thick filament is surrounded by several thin filaments

• thin filaments joined at z-line

• m-line is the center

• thick filaments are tethered to z-line by a protein called titin

shortening occurs when 2 filament types slide alongside one another

thin filaments

helical actin molecules 

each actin has myosin binding site to allow for cross-bridge formation

tropomyosin covers up binding sites used for contraction

thick filaments

myosin molecules, 2 golf-club shaped subunits

tailes aligned towards the middle

globular heads protrude out at regular intervals

• called the cross bridge, has ATP & actin binding sites

t-tubule

an extension of membrane through the muscle cell, penetrates into the interior of muscle cell

acts as the conduit for action potential propagation

sacroplasmic reticulum surrounds them and myofibrils

neural control

motor unit

• consists of muscle fibers and all muscle fibers it innervates

• varies in size w/ range of 40 or >1000 muscle fibers to unit

each muscle fiber is innervated by just one axon, but each axon branches to innervate all fibers in its unit

motor units are intercalated within bulk muscle

action potential through axon —> causes all muscle fibers in motor unit to contract

potentially needs series of AP to sustain muscle contraction

excitation-contraction coupling 

APs propagate down T-tubules and activates voltage-gated dihydropyridin (DHP) receptors

DHP activation direcetly gate open ryanodine receptors on SR membrane —> Ca2+ efflux from SR baths myofibrils in Ca2+

Ca2+ is pumped back into SR via ATP-dependent pump —> allows muscle to relax

relaxed & activated muscle

low cytosolic Ca2+

• tropomyosin covers actin binding sites

• troponin binds calcium, when it binds —> it induces a conformational rearrangement in the complex

• energized cross-bridge cannot bind to actin

high cytosolic Ca2+

• conformational rearrangement uncovers binding sites (Ca2+ binded-troponin pulls tropomyosin rope to uncover them)

• energized cross-bridge binds to actin and generates force (flexing)

sliding filament

myosin is the motor protein and actin is the highway

energized cross-bridges flex on thin filaments, pulling them closer to each other

I-band and H-band is reduced

the power stroke

1) cross-bridge binds to actin with Ca2+ increase 

2) cross bridge loses ADP & Pi and flexes, only actin bound to myosin 

3) ATP binds to myosin, causing cross-bridge to detach (M w/ ATP)

4) hydrolysis of ATP energizes cross bridge, making myosin bound to ADP & Pi

with no ATP, the cross bridges will stay bound and muscle will be forever in a contracted state (rigor moris)

muscle spindle

a sensory afferent, is a proprioceptor

stimulus that activates the 1a afferent fiber is muscle stretch, results in muscle contraction

• a sense organ that receives info. from muscle that senses speed and stretch or stretch —> sends info to alpha motor neuron to cause contraction

• when you stretch & feel message that you are at endpoint of stretch, spindle sends reflex arc signal to spinal column telling you to not stretch further

protects you from overstretching or stretching too fast and hurting yourself

golgi tendon organ

stimulus that activates the 1b afferent fiber is tendon stretch (caused by muscle contraction), results in muscle relaxation

sense organ that receives info from tendon that senses tension

• when you lift weights, golgi tendon senses and tells you how much tension the muscle is exerting —> sends info to spinal cord —> tells muscle to relax (inhibits stretched tendon & excites antagonistic muscle)

• if there is too much muscle tension, golgi tendon will inhibit muscle from creating any force (via reflex arc), protecting you from injuring yourself

extrafusal skeletal muscle fiber

highly contractile, regular muscle

intrafusal muscle spindle fiber

low contractile muscle, maintains sensitivity of muscle spindle, causes extrafusal muscle to stretch

gamma motor neurons keeps intrafusual fiber & muscle spindle calibrated to length of muscle so that it’s always in its sensitivity range

muscle tension

force exerted on an object by contracting muscle

load

froce exerted on muscle by an object

isotonic contraction

muscle changes load while load is constant

concentric contraction

shortening

eccentric contraction

lengthening

isometric contraction

muscle develops tension but does not shorten or lengthen

twitch

mechanical response of muscle fiber to single AP

isotonic

• at heavier loads

  • latent period is longer

  • shortening velocity (distance shortened per unit of time) is slower

  • distance shortened is less

tension

recruitment of more motor units by nervous system increases tension

twitch contractile activity can sum up when APs keep firing

• can sum up until tetanus (maximum sustained contraction) and then causes fatigue

length tension curve

• tells you percent of maximum tension muscle can generate based on where it is relative to resting length

• resting length —> sarcomeres are at peak muscle tension

• fewer tension opportunities when muscle is stretched or shortened

• work best in or around resting length

sacromere strength

can be stacked based on speed or strength

fast when you line them up horizontally

stronger when you stack them up vertically

muscle hypertrophy w/ weight training

hypertrophy = triggered by microtears induced by proper weight training, bigger muscle cells

low reps (1-5)

• increased neuromuscular efficiency

• no increase in size as fiber contraction force increases

medium reps (6-8)

• myofibillar hypertrophy

• increase size as fiber gains myofibrils and contraction force increases

high reps (9-15+)

• sarcoplasmic hypertrophy

• increases size as fibre gain sarcoplasm with no contraction force increase

fatigue

when skeletal muscle is repeatedly stimulated, tension the fiber develops eventually decreases even though stimulation occurs

• decline in muscle tension as result of previous contractile activity

• decreased shortening velocity & slower rate of relaxation

onset of fatigue and rate of development depends on

• type of skeletal muscle that is active

• intensity and duration of contractile activity

• degree of individual’s fitness

ATP supply (muscle

rate of ATP breakdown increases a lot with skeletal muscle fiber when it goes from rest to state of contractile activity

if fiber is to sustain contractile activity, metabolism must produce ATP as rapidly as they breakdown during contractile process

creatine phosphate

• supports first 15 seconds of contractile activity

sustained contraction requires oxidative phosphorylation and/or glycolysis

slow-oxidative fibers (type 1)

combines low myosin ATPase activity with high oxidative capacity

used for endurance, slower in contraction

fast-oxidative-glycolytic fibers (type 2A)

combines high myosin-ATPase acitivity with high oxidative capabilities and intermediate glycolytic capacity

sustains pretty well but also fatigues

fast-glycolytic fibers (type 2X)

combines high myosin-ATPase with high glycolytic capacity

fatigue rapidly

recruitment

smaller, slow-twitch fibers have low activation threshold

• first recruited when muscle contracts

• if they can’t generate amount of force for activity, fast-twitch fibers are engaged

leg muscles used for fast running over intermediate distances typically have high proportion of fast-oxidative-glycolytic fibers

blood 

made up of cells, cell fragments (leukocytes & platelets = buffy coat), and plasma

• 90% water and carries electrolytes, nutrients, waste, gases, hormones, and proteins produced by the liver like albumin and fibrinogen

erythrocytes (red blood cells)

function in O2 and CO2 transport, hemoglobin (binds O2 & CO2)

biconcave disk in shape with flexible membrane, large SA which favors diffusion

no nucleus or organelles

• no mitochondria

• no DNA, RNA (no division of mature RBCs)

glycolytic enzymes & carbonic anhydrase

lasts only 120 days, synthesized in red bone marrow by erythropoiesis, filtered by spleen and liver

• erythropoietin (hormone from kidneys) triggers differentiation of stem cells to erythrocytes

circulatory system

2 loops in system, closed system = leaks are bad

• pulmonary

  • carries O2-poor blood to lungs and back to heart

• systematic

  • carries blood cells from heart to rest of body

closed system = leaks are bad

blood from systematic loops delivers O2 to tissues and organs —> goes through pulmonary loop at O2-poor blood to the heart and to the lungs 

heart valves

1) right AV valve/tricuspid (R.A. —> R.V.)

2) pulmonary/semilunar valve (R.V. —> pulmonary artery)

• 1 & 2 are a part of pulmonary loop

3) left AV valve/bicuspid/mitral (L.A. —> L.V.)

4) aorta/semilunar valve (L.V. —> aorta)

• 3 & 4 are a part of systematic loop

when pressure is greater behind the valve, it opens

when pressure is greater in front of valve, it closes (one-way valve)

purely mechanical, no neuron control

endocardium

heart wall, thin layer of endothelial tissue lining the interior of each chamber

continuous with lining of blood vessels entering and leaving the heart

epicardium

heart wall, thin external membrane covering heart and is filled with small volume of pericardial fluid

myocardium

middle layer of heart wall, composed of cardiac muscle

cardiac muscle cells connected end-by-end by intercalated disks where 2 types of contacts are formed

• desmosomes

  • mechanically holds cells together

• gap junctions

  • provides paths of low resistance to flow of electrical current between muscle cells

  • enables cardiac function to form a functional syncytium (working as one system)

myocytes/contractile cells

99% of cardiac cells, force producing cells

contains striated muscle

muscle contraction follows myosin/actin interaction

pacemaker cells

1% of cells, electrical conduction system, doesn’t have contractile system

electrical activity of heart

heart muscle is capable of generating own rhythmic electrical activity (autorhythmic)

• occurs b/c of unique electrophysiological properties of subset of specialized cardiac muscle cells that generate pacemaker cells

• pacemaker cells are grouped into specialized regions called nodes that controls rate & coordination of cardiac contractions

  • intrinsically initiate their own APs at regular frequency

  • controlled by generation of pacemaker potentials

pacemaker potentials 

oscillation of membrane potential which causes cell to reach threshold and generate an AP at regular intervals 

VG-F type Na channel

• F = funny, depolarization

VG-T type Ca channel

• T= transient, causes to reach AP

VG-L type Ca channel (DHP channel)

• L = long-lasting, ensures broader spike

VG-Potassium channel

• several types, repolarization 

pacemaker potential steps

1) hyperpolarization leads to transient increase in Na+ permeability (VG-F), causing membrane potential to depolarize

2) depolarization causes increase in permeability to Ca2+ channel (VG-T), leading to further depolarization of membrane potential & causes cell to reach threshold

3) cell generates AP when second increase in permeability to Ca2+ occurs (VG-L)

4) depolarization resulting from AP causes increase in K+ permeability (VG-K) & membrane potential repolarizes

5) when cell repolarizes, K+ permeability decreases and process repeats

sinoatrial (SA) node

bundle of specialized cardiac pacemaker cells located in wall of right atrium near opening of superior vena cana

exhibits autorhythmicity of 70 AP per minute and leads activity of other pacemaker structures

atrioventricular node

bundle of specialized cardiac pacemaker cells located at the base of right atrium

exhibits autorhythmicity of 50 AP per minute (disconnected from SA)

under normal conditions = fast SA node at 70 AP/min

bundle of His

tract of specialized, cardiac pacemaker cells that originates at AV node and divides and projects into left and right ventricles

conducting electrical signal to multicellular pathway called synctium, causes ventricles to contract

purkinje fibers

small terminal fibers of specialized cardiac pacemaker cells that extend from bundle of His and spreads throughout ventricular myocardium

very fast conduction velocity, cerebellum of the brain, ensures ventricles contract

30 AP/min

normal conditions = follows fast AV node at 70 AP/min

interatrial pathway

pathway of specialized cardiac cells that conducts pacemaker activity from right atrium to left atrium 

fast conduction velocity

internodal pathway

pathway of specialized, cardiac cells that conducts pacemaker activity from SA-SV node

AV nodal delay

pacemaker activity is conducted relatively slowly through AV node, resulting in a delay of 100ms

ensures ventricles contract after atrial contraction

cardiac cell AP

1) very negative Vm (-90 mv) until excited

2) rising phase of AP caused by fast NA+ influx (VG-F)

3) plateau phase —> due to increase in membrane permeability to Ca2+ (VG-L) & decrease in membrane permeability to K+ (VG-K)

4) falling phase occurs when there is decrease in Ca2+ permeability & rise in K+ permeability (VG-K)

comparing heart & voluntary muscle contraction

longer AP, plateau period, does not require nerve stimulation (autorhythmic or adjacent myocyte)

Ca enters through L-type Ca channels, triggers more Ca to be released from SR

contraction occurs during AP

refractory period of heart

long twitch and prolonged refractory period (that prevents tetanus) allows time for ventricles to fill with blood prior to pumping

electrocardiogram

electrical currents generated at coordinated APs of heart muscle can reach surface of body and be detected as voltage differences between 2 points on body surface —> reading is composite of electrical activity, not a single AP

record resulting from measuring these voltage changes = ECG

disturbances in heart function detected as changes in ECG

p-wave

component of ECG that represents depolarization of atria

QRS complex

component of ECG that represents depolarization of ventricles

T-wave

component of ECG that represents repolarization of ventricles

cardiac cycle

all events involved w/ blood flow through heart occur during one heart beat

systole = ventricular contraction phase

diastole = ventricular relaxation phase

• late diastole = ventricular relaxation/filling, volume increases

• early systole = isovolumetric ventricular contraction, volume is constant

• during systole = ejection phase, volume decreases

• early diastole = isovolumetric ventricular relaxation, volume is constant, —> late diastole phase

cardiac cycle steps 

1) pressure rises, causing AV valuves to shut and SL valves are still closed (early systole)

2) ejection (pressure in lef V > aorta), ventricular volume decreases (during systole)

3) pressure in left ventricle lowers below aorta —> SL valve shuts (early diastole)

4) pressure in ventricles falls below that of atria —> AV opens (filling) (late diastole)

5) atrial contraction delivers final blood to ventricles 

end-diastolic volume (EDV)

amount of blood in ventricles at end of diastole

end-systolic volume (ESV)

amount of blood left in ventricles at end of systole

stroke volume

amount of blood ejected during systole, pumped out of chamber with each contraction

regulated extrinsically by sympathetic nervous system and intrinsically by volume of venous blood returning to ventricles

heart pumps 60% of blood aka 70 ml, varies by demand

influenced by contractility, preload, and afterload

first heart sound

low pitched, soft and relatively long-sound associated with closure of AV valves, “lub”

second heart sound

high-pitched, sharp and relatively short sound associated with closing of semilunar valves, “dup”

murmurs

abnormal heart sounds, associated with cardiac disease, due to turbulent flow of blood through malfunctioning valves

stenotic valve

stiff, narrow valve that doesn’t open completely

turbulent flow induced b/c blood must be forced through valve at high velocity

whistling murmur

insufficient valve

structurally damaged valve that does not close properly

turbulence occurs when blood flows backwards through valve and collides with blood moving in the opposite direction

swishing murmur

rheumatic fever

auto-immune disease triggered by streptococcal bacteria that leads to valvular stenosis and insufficiency, murmurs

mitral strenosis

mitral valve becomes thickened and calcified, impairing blood flow from left atrium to left ventricle, murmurs

accumulation of blood in left ventricle can cause pulmonary hypertension

septal defects

holes in septum between left and right sides of heart allows blood to pass through one side of the heart to the other (down pressure gradient), murmurs

ex. systematic blood flows into pulmonary loop

cardiac output

volume of blood pumped by each ventricle per minute, pulmonary volume is equivalent to systematic volume

determined by HR and SV, C.O. = HR x SV

average HR = 70 bpm & average SV = 70 mLs

70×70 = 4900 mLs/min = 5 liters/min

control of heart rate: parasympathetic input

supplied by vagus nerve

mediated by Ach through muscarinic receptors (HR decreases)

• Ach increases K+ channel currents, leading to more hyperpolarization

• Ach decreases F-type Na+ currents and Ca2+ channel currents, leading to shallower slope at beginning of pacemaker potential

control of heart rate: sympathetic input

sympathetic nerves supply atria (SA and AV nodes) & richly innervate ventricles

mediated by norepinephrine (NE) through beta-adrenergic receptors (HR increases)

• NE decreases K+ channel currents, leading to less hyperpolarization

• NE increases F-type Na+ currents and Ca2+ channel currents, leading to steeper slopes at beginning of pacemaker potential 

modulation of contractility: parasympathetic & Ach

atrial contractile cells

• reduces contractile strength by reducing Ca2+ permeability during plateau phase of AP —> less Ca2+ enters cells and strength of contraction reduced

little parasympathetic intervention of ventricles

modulation of contractility: sympathetic & NE

atrial and ventricular contractile cells

• increases contractile strength by enhancing Ca2+ permeability during plateau phase of AP —> more Ca2+ enters cells and strength of contraction is increased

preload

degree to which cardiac muscle cells are stretched before they contract

optimal length/tension relationship is needed for maximum force generation

frank-starling mechanism

heart muscle length doesn’t correspond to “normal resting value” or the amount the ventricles are stretched —> they are under-stretched at “rest”

increased venous return will stretch the heart muscle towards their maximized force-generating potential and the contraction will be stronger even with other factors help constant —> stroke volume increases with increasing venous return

excitation-contraction coupling in cardiac muscle

1) membrane depolarized by Na+ entry as AP begins, opens L-type Ca2+ channels in T-tubules

2)small amount of “trigger” Ca2+ enters cytosol to contribute to depolarization, which binds and opens ryanodine receptor Ca2+ channels in SR membrane

3)Ca2+ flows into cytosol, raising Ca2+ conc. 

4) binding of Ca2+ to troponin exposes cross-bridge binding sites on thin filaments 

5) cross-bridge cycling causes force generation and sliding of thick and thin filaments 

6) Ca2+-ATPase pumps return Ca2+ to SR & removes Ca2+ from cell

7) membrane is repolarized when K+ exits to end AP

arteries

composed to large vessels that carries blood away from the heart, carries oxygenated blood

pulmonary arteries carry deoxygenated blood to be oxygenated

veins

large diameter vessels formed by the merging of venules that carries blood to the heart, carries deoxygenated blood

pulmonary veins carries oxygenated blood to the heart to get sent to the rest of the body

arterioles

small diameter vessels that arise from the branching of arteries when they reach the organs they are supplying

capillaries

smallest diameter vessels that are formed when arterioles branch

venules

vessels that form when capillaries join together

microcirculation

name given to collection of arterioles, capillaries, and venules

pressure

force exerted and is measured in mmHg

flow

volume moved and is measured in mL/min

resistance

describes how difficult it is for blood to flow between two points at any given pressure difference

F= deltaP/R

increase resistance = decrease flow if pressure stays the same

factors determining blood flow

pressure gradient in vessels

resistance to flow by friction, viscosity of blood, and vessel radius

blood viscosity

friction developed in blood

determined by concentration of plasma proteins and number of circulating red blood cells

vessel length

friction between blood and inner surface of vessel is proportional to vessel length

vessel radius

friction between blood and inner surface of vessel is inversely proportional to 4th power of vessel radius

more radius = less resistance (R/4) = more flow (F⁴)

sphygmomanometer

device that is used to measure systolic and diastolic arterial blood pressure, normal = 120/80 or systolic/diastolic

listen for sound of blood squeezing past (turbulent flow) the pressure cuff

>120mmHg

• no blood flows through vessel, no sound is heard

80mmHg < pressure < 120mmHg

• blood flow through vessel is turbulent when bp exceeds cuff pressure

• intermittent sounds are heard as bp fluctuates through cardiac cycle

<80mmHg

• laminar blood flows through vessel, no sound is heard

pulse pressure

pressure difference between systolic and diastolic pressure

mean atrial pressure

pressure that is monitored and regulated by blood pressure reflexes

cardiac output (HR x SV) x total peripheral resistance (radius of arterioles and blood viscosity)

elastic arteries

conduits near heart that carries blood for circulation, aorta

large lumen vessels (low resistance) that contain more elastin than muscular arteries

“pressure reservoirs”

• expands & contacts (recoil) as blood is ejected by heart —> blood flow is continuous 

• expanding as blood comes in and recoils as blood leaves

muscular arteries

delivers blood to specific organs

proportionally the thickest media (most smooth muscle) and active in vasoconstriction

plays large role in regulation of blood pressure (mescentric artery carries 25% of cardiac output)

arterioles

smallest arteries, controlled by hormonal, neural, and local chemicals

smaller ones that lead directly into capillary beds are usually just single layer of smooth muscle which spirals around endothelium

controls minute-by-minute blood flow into capillary beds

• contract = blood flow diverted away from tissue, increase pressure

• dilate = blood flow to tissue increases, decrease pressure

magnitude & distribution of C.O. at rest and exercise

blood flow goes to area it is needed most like skeletal muscles during exercise

during exercise, blood is shunted

brain blood flow is always maintained

flow diverted to and from skeletal muscles, GI, and hearts and kidneys

• but always maintains minimal flow

vasoconstriction

increased contraction of smooth muscle in arteriolar wall, leads to increased resistance and decreased flow

too much blood flowing in

caused by

• increase in

  • O2, cold, sympathetic norepinephrine (alpha-adrenergic receptor), vasopressin, angiotessin

• decrease in

  • CO2