Physiology Exam 2

BYU Dr Woodbury Ch. 11-17

autonomic control centers

hypothalamus:

• water balance

• temperature

• hunger

pons and medulla:

• urinary

• cardiac (blood pressure)

• respiration

*both have homeostatic functions

antagonistic control of the autonomic division

one autonomic branch is excitatory, the other is inhibitory

• parasympathetic (rest & digest) and sympathetic (fight or flight)

• most organs receive input from both branches

antagonistic control: heart and veins example

parasympathetic

• slows heart rate

• no effect on veins

sympathetic

• β1 receptor: increases heart rate and contractility

• β2 receptor: dilates veins

• α receptor: constricts veins

sympathetic vs parasympathetic: basic pathway

shorter pre-ganglionic neuron in sympathetic

neuroeffector junction

synapse between postganglionic autonomic neuron and its target cells (smooth muscle)

• axon branches out and forms bulges called varicosities

properties of adrenergic receptors (sympathetic)

α receptor (intestines = constrict vessels)

• stronger norepinephrine (NE) effect

• 2nd messenger: phospholipase C

β1 receptor (heart = increase rate)

• binds NE and epinephrine equally

• 2nd messenger: cAMP

β2 receptor (lungs/muscles = dilate vessles)

• stronger epinephrine effect

• 2nd messenger: cAMP

adrenal medulla

primary neurotransmitter: epinephrine

• released to blood (many targets)

anatomy

• medulla: modified sympathetic ganglion

• cortex: endocrine tissue

comparison of sympathetic and parasympathetic branch

parasympathetic branch

neurotransmitter: only acetylcholine (ACh)

receptors: muscarinic

• G-protein coupled, 2nd messenger pathways

functions:

• constrict pupils and bronchioles

• slows heart

• stimulates digestion

• stimulates insulin release

• stimulates urination

eye dilation example

sympathetic: controls radial muscles = DILATION

parasympathetic: controls circular muscles = CONSTRICTION

autonomic system agonists and antagonists

sympathetic agonist: mimics the effect of norepinephrine

sympathetic antagonist: blocks the effect of norepinephrine

parasympathetic agonist: mimics the effect of acetylcholine

parasympathetic antagonist: blocks the effect of acetylcholine

somatic motor division

single neuron originates from CNS (myelinated)

• axon branches at neuromuscular junction

neuromuscular junction

consists of: axon terminals, motor end plates on muscle membrane, and Schwann cell sheaths

nicotinic acetylcholine receptors (somatic)

nicotinic receptor

• 2 acetylcholine molecules bind

• opens a non-specific monovalent cation channel (both K+ and Na+ can go through)

• more Na+ goes in than K+ goes out due to voltage difference (negative inside cell)

• cell depolarizes and sends action potential down whole muscle

efferent pathways: somatic motor, parasympathetic, sympathetic, adrenal sympathetic

somatic vs autonomic division

three types of muscle

skeletal muscle

• multinucleated (many cells fused together)

• striated

cardiac muscle

• single nucleated

• striated

• intercalated disks (connected by gap junctions)

smooth muscle (stomach, bladder, blood vessels)

• single nucleated

• not striated

• sometimes gap junctions

antagonistic muscle groups

biceps and triceps

• extension: when tricep contracts, bicep relaxes

• flexion: when bicep contracts, tricep relaxes

skeletal muscle anatomy

• tendon: made up of muscle fascicles

• muscle fascicle: made up of a bundle of fibers

• muscle fiber: made up of bundles of proteins called myofibrils

skeletal muscle fiber components

• myofibril: bundles of contractile and elastic proteins

• sarcolemma: cell membrane

• sarcoplasm: cytoplasm

• sarcoplasmic reticulum: modified ER, wrap around myofibril, contains Ca2+

• t-tubules: extension of cell membrane, carry action potential through muscle

• sarcomere: basic functional unit of contraction, make up myofibril

sarcomere structure

filaments:

• thick: mysoin

• thin: actin chains, troponin, tropomyosin

bands:

• A band: myosin

• I band: region between A bands (actin chain only)

• H zone: part of myosin (A band) that doesn’t overlap with actin

• M line: middle of A band where myosin attached

• Z disk: end of sarcomere, where actin chains branch out

components:

• titin: elastic protein

• nebulin: helps align actin

• troponin & tropomyosin: regulatory, interact with actin

muscle contraction pathway

1. Event at neuromuscular junction

2. Excitation-contraction coupling

3. Ca2+ signal

4. Contraction-relaxation cycle

5. Muscle twitch & sliding filament theory

changes in sarcomere length during contraction

sarcomere: shrinks

A band: stays constant

I band: shrinks

H zone: shrinks

contraction - myosin power stroke

1. Rigor state: myosin tightly bound

2. ATP binds: myosin releases actin

3. ATP hydrolysis: myosin cocks forward

4. Release Pi: power-stroke

5. Release ADP: rigor state, myosin bound

regulation by tropomyosin and troponin

Relaxed state:

• tropomyosin blocks myosin-binding site on actin

Contraction:

• Ca2+ binds troponin

• tropomyosin moves away from myosin-binding site

• myosin binds to actin (power stroke)

• actin filament moves

Ending contraction:

• Ca2+ actively transported back into sarcoplasmic reticulum

• Ca2+ no longer binds troponin

• tropomyosin covers up myosin-binding site again

excitation-contraction coupling

1. Somatic motor neuron releases acetylcholine at neuromuscular junction

2. Entry of Na+ through receptor-channel initiates muscle action potential

3. Action potential in t-tubule changes conformation of DHP receptor

4. DHP receptor opens gate in sarcoplasmic reticulum to release Ca2+ (which binds to troponin)

contraction-relaxation cycle

neuron and muscle action potentials within 2 ms

contraction-relaxation of muscle is longer (10-100 ms)

phosphocreatine

phosphocreatine: reserve of energy created during resting

ATP + creatine → ADP + phosphocreatine

• enzyme: creatine kinase

• fwd direction during resting

• reverse direction during working

ATP used for:

• Myosin ATPase (contraction)

• Ca2+ ATPase (relaxation)

• Na+-K+ATPase (restore ions after movement during action potential)

muscle fatigue

central fatigue: psychological effects, protective reflexes, decrease in neurotransmitter release

peripheral fatigue: decrease neurotransmitter release, change in membrane potential, decrease Ca2+ release, decrease Ca2+-troponin interaction

extended submaximal exertion:

• depletion of glycogen stores

• increase intracellular K+

short-term maximal exertion:

• increase inorganic phosphate (slows Pi release from myosin)

• decrease Ca2+ release

red vs white muscle

red muscle is due to:

1. high myoglobin concentration (high oxygen reserve)

2. high capillary density

3. more mitochondria

Type I & Type IIA = red muscle

Type IIB = white muscle

types of muscle fibers: Type I

slow-twitch oxidative

• red muscle - small diameter, darker red color

• slower development of tension (slow myosin ATPase activity)

• long contraction duration (lower Ca2+ ATPase activity in SR)

• fatigue-resistant

• oxidative, aerobic metabolism

• high capillary density

• high # of mitochondria

• high myoglobin

types of muscle fibers: Type IIA

fast-twitch oxidative-glycolytic

• red muscle - medium diameter, red color

• intermediate development of tension (fast myosin ATPase activity)

• short contraction duration (high Ca2+ ATPase activity in SR)

• fatigue-resistant

• glycolytic but can become more oxidative with training

• medium capillary density

• moderate # of mitochondria

• high myoglobin

types of muscle fibers: Type IIB

fast-twitch glycolytic

• white muscle - large diameter, pale color

• fastest development of tension (fast myosin ATPase activity)

• short contraction duration (high Ca2+ ATPase activity in SR)

• easily fatigued

• glycolytic, more anaerobic

• low capillary density

• low # of mitochondria

• low myoglobin

muscle training

training = more endurance = more mitochondria = more cytochrome C

stop training = mitochondria decrease

• takes energy to maintain muscle

type I & IIA used for jogging and moderate intensity running

type IIB used for high-intensity exercise, can be converted to IIA with training

sarcomere length-tension relationship

the optimal length of a sarcomere has all myosin heads lined up with actin (produces maximum tension)

• too short = actin overlaps

• too long = myosin heads don’t overlap with actin

contraction summation

single twitches: muscles relaxes completely between stimuli

summation: closer together stimuli

• more Ca2+ release before all the Ca2+ is pumped back into SR (so more tension)

incomplete/unfused tetanus: muscle reaches maximum tension but can relax slightly between stimuli

complete/fused tetanus: muscle reaches steady maximum tension, leading to fatigue

• decrease in tension even when action potentials are still firing

motor units

motor unit = one motor neuron and its muscle fibers

• one muscle contains multiple motor units of different types

• tension is determined by how many muscle fibers are recruited and the frequency of action potentials

isotonic vs isometric contractions

isotonic:

• enough force to move load

• muscle contracts and shortens

isometric:

• not enough force to move load

• muscle contracts but doesn’t shorten

series elastic elements

isotonic:

• series elastic elements are fully stretched

• sarcomeres continue to shorten, causing whole muscle to shorten

isometric:

• series elastic elements stretch as sarcomeres shorten

• overall length of muscle stays the same

lever & fulcrum system of arm

elbow is fulcrum

• need a balance of rotational forces to hold arm steady (weight of arm vs force from biceps)

biceps attachment point is 5cm from fulcrum

• trade-off between velocity of contraction (closer to fulcrum) and weight that can be lifted (further from fulcrum)

muscle disorders

muscle cramps: sustained painful contraction

overuse

disuse: atrophy

acquired disorders: influenza, botulinum, tetanus

inherited disorders:

• McArdle’s disease: loss of enzyme that converts glycogen to gluc-6-phos

• Duchenne’s muscular dystrophy: loss of structural protein dystrophin

relative contraction times for different types of muscle

action potential: milliseconds

skeletal: fast, <0.5 sec (fast-twitch is faster)

cardiac: less fast, ~1 sec

smooth: slow, several seconds

smooth muscle properties

• uses less energy

• maintains force for long periods

• low oxygen consumption

• longer actin and myosin filaments

• slower myosin ATPase activity

• myosin light chain plays regulatory role

• Ca2+ enters from both sarcoplasmic reticulum and ECF

smooth muscle contractions (tonic vs phasic)

phasic: periodic contraction & release cycles

tonic: continually contracted

single-unit vs multi-unit smooth musclle

single-unit:

• varicosities on surface

• connected by gap junctions

• all contract together

multi-unit:

• varicosities throughout muscle cells

• not connected by gap junctions

• each cell stimulated independently

anatomy of smooth muscle

meshwork of actin and myosin fibers around outside of muscle cells

• attached by protein dense bodies

• cell becomes globular when it contracts

myosin heads across whole length

• myosin can slide across actin for long distances

smooth muscle contraction

1. Increase conc. of intracellular Ca2+

2. Ca2+ binds calmodulin

3. Ca2+-calmodulin activates myosin light chain kinase (MLCK)

4. MLCK phosphorylates myosin light chains

5. myosin ATPase activity increases

6. muscle tension increases

smooth muscle relaxation

1. Ca2+ pumped out of cell and into SR

2. Ca2+ unbinds calmodulin

3. Myosin phosphatase dephosphorylated myosin

4. myosin ATPase activity decreases

5. muscle tension decreases

control of smooth muscle contraction

IP3: second messenger, activates contraction

modulatory pathways: change activity of MLCK or myosin phosphatase

stretch-activated calcium channels: open when pressure or other force distorts cell membrane (myogenic contraction)

membrane potentials in smooth muscle

slow wave potentials: cyclic, fire when reach threshold

pacemaker potentials: always depolarize to threshold

pharmacomechanical coupling: tension changed by chemical signal without change to membrane potential (ex, histamine, nitric oxide)

comparison of skeletal, cardiac, and smooth muscle

reflex classification

1. autonomic or somatic

2. integration in spinal cord or brain

3. innate or learned

4. monosynaptic or polysynaptic

monosynpatic somatic motor reflex

somatic, spinal, innate, monosynaptic

polysynaptic somatic motor reflex

interneuron in spinal cord

autonomic reflexes

proprioreceptors

Muscle spindles and Golgi tendon organs are sensory receptors in muscle that respond to movement and tension

• muscle spindles = length

• Golgi tendon organs = tension

muscle spindles

monitor muscle length (and change in length) and prevent overstretching

• gamma motor neurons contract intrafusal fibers, alpha motor neurons contract muscle itself

• sensory neuron tonically activated - communicating info abt length of muscle

muscle spindles: contraction

unintentional contraction = negative feedback

• stretch of muscles increases signal frequency to spinal cord

• response is alpha motor neurons signal muscle to contract

• signal frequency to spinal cord is decreased

intentional contraction = alpha gamma coactivation

• spindles (gamma motor neuron) contract proportionally to muscle contraction (alpha motor neuron)

• sensory neuron signal frequency is unchanged

goal: send info about mismatches

Golgi tendon organ

monitor muscle tension

• neurons interweave collagen fibers

• tension pulls on the collagen fibers and pinches neurons

• sends inhibitory input to prevent excessive contraction

knee jerk reflex

1. tap to tendon stretches muscle

2. muscle spindle stretches and fires

3. action potential travels through sensory neuron

4. sensory neurons synapse in spinal cord

Outgoing paths:

1. somatic motor neuron - contract quadriceps

2. interneuron inhibiting somatic motor neuron - relax hamstring (reciprical inhibition)

3. send information up to brain

flexion reflex and crossed extensor reflex

1. painful stimulus (step on a tack)

2. primary sensory neuron enters spinal cord and diverges

   1. activate ascending pathway for pain

   2. activate descending pathway for postural adjustment

3. withdrawal reflex - pull foot away

4. crossed extensor reflex supports body as weight shifts

   1. side of stimulus: extensors inhibited, flexors contract

   2. other side: flexors inhibited, extensors contract

types of movement

1. reflex (knee jerk, postural reflexes) - integrate in spinal cord

2. voluntary (playing piano) - integrate in brain

3. rhythmic (walking, running) - integrate in spinal cord with brain input required

voluntary movements - CNS integration

1. Sensory input: receptors → sensory cortex

2. Planning and decision making: prefrontal cortex, other areas of brain

3. Coordination and timing: cerebellum input

4. Execution: motor cortex → spinal cord → skeletal muscles

5. continuous feedback

cardiovascular system: material movement

materials entering body: oxygen, nutrients, water

materials moved from cell to cell: waste, immune cells, hormones, stored nutrients

materials leaving body: metabolic waste, heat, CO2

cardiovascular system: overview

blood pumped from right heart → lungs → left heart → rest of body

• portal system from digestive tract straight to liver

cardiovascular system: pressure gradient and blood pressure

blood pressure drops from left side of heart → capillaries → right side of heart

• driving pressure created from contraction of left ventricle

• as fluid flows, pressure is lost due to friction

• dilation of blood vessels causes pressure decrease

• volume changes are major factors for blood pressure

cardiovascular system: pressure & fluid flow through a tube

hydrostatic pressure: mass per unit area or column height

• units: mm of Hg (torr), cm of water, atmospheres, bars, Pascals

fluid flow: how much blood flows past a given point

• flows only if there is a positive pressure gradient

• increase radius = increase flow, deceases resistance

• increase length of tube = decrease flow, increase resistance

cardiovascular system: velocity

velocity: how fast blood flows past a point

• narrower vessel - faster velocity

• from arteries to capillaries, cross sectional area increases and velocity decreases

  • want slower blood so exchange can happen

heart anatomy

heart valves ensure one-way flow

• right AV valve (tricuspid)

• left AV valve (bicuspid)

• pulmonary valve

• aortic valve

cardiac muscle

compared to skeletal muscle, cardiac muscle has:

• smaller fibers

• single nucleus per fiber

• high amount of mitochondria (1/3 of cell volume)

• larger, branching t-tubules

• smaller sarcoplasmic reticulum

intercalated disks: gap junctions (electrical connection) and desmosomes (transfer of force)

cardiac muscle contraction

1. Action potential

2. voltage-gated Ca2+ channeles open

3. Ca2+ enters cell from ECF

4. Ca2+ is released from sacroplasmic reticulum (Ca2+ spark)

5. Ca2+ binds troponin → contraction

6. Ca2+ pumped back into SR (active transport), pumped out of cell (Na/Ca exchanger, secondary active transport)

myocardial action potential

longer than nerve action potential: 200-300 ms

• short depolarization, long repolarization

• opening of Ca2+ channels (Ca2+ goes in) sustains depolarization

• repolarization occurs when Ca2+ channels close and K+ channels open

myocardial refractory period

no summation of myocardial action potentials

• refractory period is almost as long muscle twitch

• can’t create another action potential

• prevents tetanus

types of cardiac cells

myocardial contractile cells

• electrically connected by gap junctions

• contain actin and myosin

• produce force

autorhythmic (pacemaker) cells

• different action potential

• electrically connected by gap junctions

• “funny” channel allows membrane potential to spontaneously depolarize to threshold

• no actin and myosin

autorhythmic cell action potential

1. Funny channels open and allow K+ and Na+ through (net Na+ in)

2. Closer to threshold, funny channels close and Ca2+ channels open

3. At threshold, more Ca2+ channels open and Ca2+ rushes in

4. At peak, Ca2+ channels close, and slow K+ channels open (K+ goes out)

5. At valley, K+ channels close and funny channels open

modulation of heart rate by nervous system

sympathetic stimulation:

• depolarize pacemaker cells

• speed up depolarization rate

• increases influx of Na+ and Ca2+

parasympathetic stimulation:

• hyperpolarize pacemaker cells

• slows depolarization

• increases efflux of K+ and decreases influx of Ca2+

electrical conduction in heart

SA node sets heart pace, action potential begins here and spreads to contractile cells.

• If SA node fails, AV node will set pace

• If AV node fails, Purkinje fibers will set pace

Process:

1. SA node depolarizes

2. Depolarization spreads to atrium and AV node

3. AV causes signal to stall to atria can finish contracting first

4. Depolarization moves through ventricular conducting system to bottom of heart

5. Ventricles contract from bottom up to eject blood to valves

Einthoven’s triangle

3 nodes: right and left arm, left leg

3 leads: pairs of nodes

• 3 different images of heart’s electrical signal

most ECG’s use 12 nodes

ECG trace

Waves in ECG

• P wave: atria depolarize

• QRS complex: ventricles depolarize, atria repolarize

• T wave: ventricles repolarize

normal vs abnormal ECG

abnormal ECG

• 3rd degree block: SA fires normally, ventricles don’t get signal and fire spontaneously

• atrial fibrilation: atria contract non-synchronously, not life-threatening

• ventricular fibrilation: ventricles contract non-synchronously, life-threatening

pulse felt at wrist = R waves, heart rate = P waves

mechanical events of cardiac cycle

1. Late diastole: all chambers relaxed, ventricles fill passively

2. Atrial systole: atrial contraction, force additional blood into ventricles (largest amount of blood in ventricles = EDV)

3. Isovolumic ventricular contraction: AV valves close, ventricles contract with no volume change

4. Ventricular ejection: ventricles contract, semilunar valves open, blood is ejected

5. Isovolumic ventricular relaxation: ventricles relax

cardiac cycle - pressure and volume

A→B: blood comes back to heart, left atria contract

B: end diastolic volume (EDV) - end of heart relaxation

B→C: contraction, no valves open

C→D: valves open, volume decrease as blood goes out

D: end systolic volume (ESV) - aortic valve closes, 2nd sound

D→A: ventricle relaxes

Wigger’s diagram

atrial systole:

• increase volume: ventricles filling

• depolarization pass through to ventricles

isometric ventricular contraction:

• AV valve closes (sound 1)

• atrial and ventricular pressures deviate

• ventricular pressure spikes

• volume constant

ventricular systole:

• aortic valve opens

• volume decreases: blood leaves to aorta

• aortic and ventricular pressure are the same

ventricular diastole:

• aortic valve closes (sound 2)

• dicrotic notch: blood bounces back, loses ‘push’ of ventricle when valve closes

• ventricular pressure deviates from aortic pressure and lines up with atrial pressure again

• increase volume: passive filling of ventricle

heart sounds

1st heart sound: AV valves close

2nd heart sound: aortic valves close

heart murmurs: caused by leaky or stenotic heart valves

• stenotic = stiff and narrow, more resistance to flow

stroke volume and cardiac output

stroke volume: amount of blood pumped by one ventricle during contraction

• SV = EDV - ESV

cardiac output: volume of blood pumped by one ventricle in a given period of time

• CO = stroke volume x heart rate

• average is 5 L/min

Frank-Starling law

As EDV (stretch) increases, so does stroke volume (force)

• more blood going into heart, more force of contraction

Sarcomere resting length is shorter than optimal

• when heart is stretched, it becomes optimum length and there is more actin-myosin overlap, allowing for greater force of contraction

inotropic effects

Norepinephrine increases contractility of the heart

• when graph levels off: no more force when blood coming into heart is increased = heart failure

• norepinephrine can help prevent heart failure

factors affecting venous return

1. Low pressure gradient: further from high-pressure area of arteries

2. Veins have low resistance to flow: big, flaccid vessels

3. One-way valves in veins prevent backflow

4. Muscle pump: contraction of muscle pushes blood toward heart

5. Respiratory movements: during respiration, pressure in thorax decreases, pulls blood into chest (negative pressure)

6. Sympathetic vasoconstriction of veins: decreases volume reservoir, sending more blood to heart

factors that affect cardiac output

heart rate:

• determined by rate of depolarization in autorhythmic cells

• modulated by parasympathetic and sympathetic

stroke volume:

• determined by force of contraction

• contractility

• end-diastolic volume

• modulated by sympathetic - venous constriction & venous return

cardiovascular system: functional model

arteries: elastic, pressure reservoir

arterioles: site of variable resistance, adjust diameter

capillaries: exchange, low velocity

veins: volume reservoir, constrict to push more blood through

blood vessel structure

aorta: large diameter, thick wall, elastic and fibrous tissue

arteriole: smaller diameter, thinner wall, smooth muscle

capillaries: smallest diameter, thin wall, just endothelium, good for exchange because they lack smooth muscle and elastic tissue reinforcement

venule: more fibrous tissue

vein: thick, more tissue types

angiogenesis

angiogenesis: new blood vessel development

• necessary for normal development

• wound healing, uterine lining growth

• controoled by cytokines

• relevant in cancers and coronary heart disease

arteries pressure reservoir

ventricles contract: blood pushed into arteries, walls stretch

• presure stored in elastic walls

ventricles relax: aortic valve closes, elastic recoil of arteries pushes blood through rest of circulatory system

pulse pressure

pulse pressure = systolic pressure - diastolic pressure

mean arterial pressure = diastolic pressure +1/3(pulse pressure)

• estimate of integration under the curve (cyclic)

• proportional to cardiac output x arteriole resistance

measuring blood pressure

blood pressure cuff: increase pressure to collapse artery

• greater than 120: no sound, artery is collapsed (decrease until hear sound = systolic pressure)

• between 80 and 120: Korotkoff sounds (decrease until no sound = diastolic pressure)

• below 80: no sound, regular blood flow

control of blood pressure

increase blood volume = increase blood pressure

• fast response: vasodilation, decrease cardiac output = drop BP

• slow response: kidneys excrete fluid in urine, decrease blood volume = drop BP

mean arterial pressure

factors influencing mean arterial pressure

• blood volume: fluid intake and loss, regulate by kidneys

• cardiac output: heart rate, stroke volume

• resistance: arteriole diameter

• relative distribution of blood between arterial and venous blood vessels: vein diameter

chemicals influencing vasoconstriction and vasodilation

vasoconstriction:

• norepinephrine on alpha receptors

• serotonin

• vasopressin (increase BP in hemorrhage)

• angiotensin II (increase BP)

vasodilation:

• epinephrine on beta2 receptors

• nitric oxide NO (paracrine)

• adenosine (paracrine, increase blood flow to match metabolism)

• increase O2, decrease CO2, increase H+, increase K+ (increase blood flow to match metabolism)

renin-angiotensin system

kidney: detects BP, when BP drops releases renin hormone

renin: converts angiotensin (from liver) to angiotensin I

converting enzyme (in lungs and capillaries): convert angiotensin I to angiotensin II

angiotensin II:

• fast response: constrict arterioles, increase resistance, increase BP

• slow response: promotes release of aldosterone from adrenal cortex

aldosterone: decreases loss of sodium in urine from kidneys

• blood volume increases → blood pressure increases

arteriolar resistance

• myogenic autoregulation: stretch-activated Ca2+ channels n smooth muscle

• paracrines: active and reactive hyperemia, NO, adenosine, O2/CO2

• sympathetic control