FHB Section 1 Review Questions

Q: Draw the neuronal action potential graph for motor neuron, skeletal muscle and cardiac
ventricle
A: Motor neuron: resting potential at -70, depolarization to +30, hyperppolarization. Skeletal
muscle: resting -90, depolarization, longer than motor neuron, slower final repolarization. Cardiac
ventricle: resting -90, depolarization, slow / long AP (100X slower than motor). Overshoot = +
over 0mV
Q: What extracellular molecule do the upstroke, repolarization, and long repolarization depend
on?
A: Upstroke = Na+, Repolarization = K+, Long repolarization = Ca2+.
Q: Describe the Na+ Channel gating properties (specific for both gates)
A: -90mV M gate closed, Activated AP Na+ floods with M&H gates open. There is a positive
feedback cycle as more Na+ channels open. Time and voltage dependent H gate closes (+10mV),
recovery to resting. Whole kinetics take .5ms. M gate stays open as long as cell is depolarized.
Q: What effect does Fugu & TTX toxin have on Na+ channels? What type of drug correlation is
there?
A: Blocks inactivated sodium channels, prevents reactivation. Antiarrhymic class 1 drugs do the
same thing
Q: What percentage of cells are available for depolarization at resting? What clinical coorelation
does this have?
A: 80%, patholigical situations alter membrane potentials, slows conduction
Q: Explain absolute vs relative refractory period. What is that based off of?
A: Absolute = time when stimulus cant elicit regenerative response, Relative = time when
sufficient stimulus can elicit regenerative response. First goes through absolute then relative as
the membrane repolarizes. Absolute also includes the initial depolarization AP. Refractory periods
are based on voltage-dependent inactivation of Na+ channels
Q: Describe K+ channels inactivation gates. What direction does K+ flow upon depolarization?
A: TRICK QUESTION. K+ channels dont have gates, but remain open with membrane
depolarization. They deactivate with repolarization. K+ flows out of cell
Q: Describe hyperkalemia effects on RMP, Na+ channels & conduction. What 2 signs/symptoms
are there?
A: RMP becomes more positive, Na+ channels inactivate, conduction slows. Signs are slow
mentation and muscle weakness

Q: Describe hyper and hypocalcemia effects on RMP & [Ca 2+], discuss membrane excitability.
Discuss respiratory hyperventilation & hypoventilation
A: Hypercalcemia = high extracellular [Ca2+], raise threshold for Na channel activation, dec
membrane excitability. Hypoventilation respiratory acidosis, inc [CO2] [Ca2+], dec membrane
excitability. Hypocalcemia = low extracellular [Ca2+], lower threshold for Na channel activation,
inc membrane excitability. Hyperventilation respiratory alkalosis, dec [CO2] [Ca2+], inc
membrane excitability
Q: What effect does myelination have on conduction velocity, membrane resistance, and length
constant? What are unmyelinated parts called? What does MS & diabetic neuropathy do to this?
A: Significantly greater conduction velocity by increasing membrane resistance and length
constant. Node of Ranvier are where no Schwann cell myelin. MS & diabetic neuropathy
destroys myelination, severely slowing conduction
Q: Explain difference between excitatory post-synaptic potential (EPSP) & inhibitory postsyndaptic potential (IPSP), include neurotransmitter, influx ion, membrance potential change, and
probability of AP firing.
A: EPSP = excitatory (Ach/glutamate), Na in K out, towards 0mV, increase AP fire. IPSP =
inhibitory (GABA/glycine), Cl in, towards -65mv (Cl), dec AP fire.
Q: Describe the difference between Temporal vs Spatial summation at the axon hillock.
A: Spacial = different locations, same time. Temporal = same place, very close time. If net
summation meets threshold then it fires.
Q: Neuron-viscera uses en passant & varicosities, what does that mean?
A: In passing, the NT is just released in a nearby area, that effects it
Q: What is the difference between Nicotinic & Muscarinic cholinergic receptors?
A: Nicotinic = very fast. Ex: skeletal muscle, post gang neurons, Adrenal medulla
Muscarinic = slower, G protein coupled. Ex: effector organs (parasympathetic), Sweat glands
(symp)
Q: What is the difference between visceral and vascular smooth muscle innervation?
A: Visceral varicosities go to all cells in all layers. Vascular only has outer layer varicosities
which allows for endothelial response that can counteract the ANS
Q: Describe adrenergic transmission to smooth muscle, start with the NT synthesis
A: DOPA dopamine NE synthesized in granular vesicle. AP arrives, releasing granular
vesicle which releases NE. NE acts on 2 adrenoreceptor in ganglion and 1 adrenoreceptor in
smooth muscle. NE is reuptaken and destroyed by MAO & COMT (monomaine oxidase &
catechol O-methyl transferase)

Q: Describe Cholinergic transmission, start with neurotrasnmitter.

A: Ach synthesized from choline by choline acetyltransferase (egg yolk, liver, soy), transported to
agranular vesicle. Ach released, acts on Muscarinic receptors. Ach inactived by hyrolysis via
AChE (acetyl cholinesterase) to choline, choline uptaken for reuse.
Q: Describe sympathetic and parasympathetic synapse receptors for both pre and post ganglionic
neurons. Discuss neuron length, NT, receptor types & speed.
A: Symp: short pregang, long post gang, synapse in paravertebral and prevertebral ganglia,
pregang uses Ach with nicotinic receptors, post gang uses NE / E with adrenergic receptors 1,2
and 1,2,3. Parasymp: long pregang, short post gang, pregang uses Ach with nicotinic receptors,
post gang uses Ach with muscarinic (M1-5) slow receptors. Sweat glands are post gang
sympathetic but have muscarinic Ach receptors. Renal vessels have dopamine receptors.
Q: What type of visceral afferent info travels in symp and parasymp fibers? What is referred
pain?
A: Symp = pain through reflex arcs. Parasymp = non-pain reflexes (baroreceptor reflex),
triggered by glutamate. Referred pain is visceral pain that is perceived as originating elsewhere
due to convergence of somatic and visceral afferent fibers.
Q: How does the Baroreceptor reflex work to control blood pressure (start with inc pressure)?
A: Carotid artery stretch, activates mechanoreceptor increasing firing rate, CN IX to medullar
cardioregulatory/vasomotor centers. Increase parasymp stim to heart to decrease heart rate (M2
receptor). Decrease symp stim to heart (dec heart rate, stroke volume, adrenergic receptor),
decrease symp to vascular smooth muscle for relax (1 adrenergic receptor withdraw), decrease
symp to adrenal chromaffin (dec NE/E output, decreases pheripheral / receptors activation)
Q: What are the autonomic centers in the brain? (5)
A: Reticular formation (medulla) = vasomotor/vasodilator, respiratory control, water intake. Pons
= respiratory control, micturitation. Hypothalamus = temp reg, water/food intake, fight, flee,
reproduction. Amygdala = limbic system, emotions, learned fear. Cortex.

Q: What are the steps in EC coupling & muscle contraction?

A: 1. Excitation-Contraction coupling
a. AP travels to T-tubule
b. Depolarization activates DHPR (dihydropyridine receptor)
c. DHPR change activates RyR (Ryanodine receptor)
d. RyR releases Ca2+ from SR (sarcoplasmic reticulum)
e. Ca2+ initiate muscle contraction
f. SERCA (Sarc and Endo Reticulum Ca ATPase) pump Ca2+ back to SR lumen
(muscle relax)
2. Ca2+ binds troponin
3. Troponin/tropomyosin move to actin groove
4. Myosin binds actin
5. Crossbridge cycle/powerstroke

6. Ca2+ sequestration (relaxation)

Q: What are the different methods to regulate muscle contraction strength?
A: Twitch summation, Recruitment of motor units, Muscle fiber thickness, Length-tension
relationship
Q: What is Twitch summation and what effect does it have on the fiber? What is Tetanus?
A: Frequency of the AP to 1 myofiber, increases [Ca2+], inc available actin = more contraction.
Tetanus is the maximum frequency and tension before fatigue.
Q: Describe recruitment of additional motor units.
A: Recruit additional motor units to add contractile force as needed for the task
Q: What are the different ways to increase muscle fiber thickness? What are the clinical correlates
(think heart)? How much force per sarcomere?
A: Each sarcomere ~.3N. Increase in series. Ex: leaky heart will increase the shortening ability
but not contraction force due to more sarcomeres in series. Increase in parallel. Ex: hypertension
will increase contraction force by parallel but not shortening ability.
Q: What is the length of fiber at contraction start have to do with contraction strength?
A: Sarcomere too short = steric hindrance. Sarcomere too long = not enough crossbridge. LengthTension relationship where equal length or slightly past has max force.
Q: Draw the force-velocity relationship for muscles. What determines maximum velocity and
maximum load?
A. Hyperbolic shape. Max velocity determined by actin/myosin
ATPase activity. Max load with no shortening by number of
actin/myosin interactions (crossbridges).

Q: What are the 5 types of muscle contraction?

A: Concentric (active short), Eccentric (active long injury & strength), Isometric (fixed length),
Isotonic (active w/ constant force/load), Passive stretch (passive lengthening from Titin within
fiber heart disease)
Q: Describe the difference between isometric and isotonic muscle contraction.
A: Isometric will have same length, Isotonic will have the same tension.

Q: Describe difference in E-C coupling between skeletal and cardiac muscle.

A: Skeletal uses DHPR (dihydropyradine receptor) with physical coupling. Cardiac uses Ca 2+
induced Ca2+ release.
Q: What are the 3 sources for muscle ATP? Mention muscle color, mitochondria/vessel amt
A: 1. Creatine phosphate: (Creatine-P + ADP Creatine + ATP) = rapid 1st release of ATP. 2.
Oxidative Phosphorylation: Mitochondria + O2 efficient but slow for 30 ATP, these muscles are
red due to myoglobin, mitochondria, and blood vessels. 3. Glycolysis: fast, less efficient for 6
ATP, lactate, muscles are whiter due to less myoglobin, mitochondria, and less vessels
Q: What are the 3 muscle types, discuss glycolysis/oxidative use, twitch speed & fatigue
A: Type 1: slow, endurance / slow fatigue, sustained tonic, oxidative for energy after creatine,
postural muscles, marathon runner, lots mitochondria/blood vessels/myoglobin. Type IIA Red:
fast, slow fatigue, sustained phasic, glycolysis after creatine and highest oxidative, lactate. Type
IIB White: fast, fast fatigue, short phasic, high glycolysis, low oxidative.
Q: Describe smooth muscle t-tubules and electrical/chemical conduction.
A: TRICK QUESTION! Smooth muscle has caveolae (membrane invaginations) and gap
junctions for electrical coupling and chemical communication.
Q: Describe smooth muscle E-C coupling mechanism. Start with Action Potential, discuss both
tension and tonic tension results
A: AP arrives Voltage Ca2+ channels open Increase in [Ca2+] Ca2+-calmodulin binds
Ca2+Cal activates myosin-light-chain-kinase (MLCK) MLCK ~P myosin Crossbridge
formation uses ATP tension. OR de~P myosin by myosin-light-chain-phosphatase (MLCP)
myosin + actin latch bridge formation tonic tension (doesnt need ATP)
Q: Diagram how Voltage gated, Ligand gated, and IP3 gated Ca2+ channels involve with E-C
coupling
A: Voltage gated: AP arrives, membrane depolarizes, Ca 2+ enters cell, Ca-Cal binds, etc. Ligand
gated: hormone/NT binds to receptor protein, opens Ca2+ channel, etc. IP3 gated: hormone/NT
binds to receptor, phospholipase C cleaves PIP2 IP3, IP3 goes to sarcoplasmic reticulum and
binds, SR releases Ca2+ into cell, etc
Q: Describe difference between electro-mechanical & pharmaco-mechanical coupling
A: Electro-mechanical is by action potential or membrane depolarization that opens a voltage
gated channel (NT diffusion or gap junctions junctions between receptors). Pharmaco-mechanical
coupling is through hormones / ligands that open a channel via a receptor protein. UNSURE
ABOUT THIS ONE
Q: What effect does the IP3 pathway have on smooth muscle activation?
A: IP3: causes release of Ca2+ from SR via IP3 receptor, leading to MLCK dependent contraction
via Ca2+-Calmodulin

Q: What effect does the cAMP pathway have on smooth muscle activation?
A: cAMP stimulates PKA (protein kinase A) to phosphorylate MLCK which 1) decreases its Ca 2+
sensitivity and 2) increases sarcoplasmic reticulum Ca 2+ pumping, smooth muscle relaxes (2
adrenergic receptor). Adrenaline will work by activating a -receptor which makes cAMP
Q: What effect does the cGMP pathway have on smooth muscle activation?
A: cGMP stimulates MLC phosphatase which decreases myofilament activation causing smooth
muscle relaxation
Q: What effect does the nitric oxide (NO) have on smooth muscle activation? How is NO
released? What is the effect when there is no NO and no endotheial cell and there is Ach?
A: Endothelial cells release NO when stimulated by Ach. NO activates cGMP, which stimulates
MLC phosphatases that cause smooth muscle relaxation. When there is no NO, Ach causes
smooth muscle contraction.
Q: What effect does caffeine have on smooth muscles, describe the mech? How does viagra work
similarly?
A: Caffeine works by preventing breakdown of cAMP by phosphodiesterase this leads to
decreased Ca2+ sensitivity and increase Ca pumping into SR for smooth muscle relaxation.
Viagra prevents breakdown of cGMP which works through MLC phosphatase and causes smooth
muscle relaxation.
Q: Explain the effect of voltage gated Ca2+ channels on smooth muscle activation.
A: Voltage gated Ca2+ channels, varies the amount of Ca2+ and therefore the contraction
Q: Explain the effect of ligand bound Ca2+ channels on smooth muscle activation. How does all
this tie in with CICR (Ca2+ induced Ca2+ release)?
A: Ligand binding allows Ca2+ to enter cell which indirectly causes voltage gated Ca 2+ channels to
open due to the change in membrane potential, this leads to contraction. CICR is when Ca 2+
causes activation and release of intracellular Ca 2+ stores (like SR) so there can be amplified
contraction through Ca-CaM and MLCK via highly increased intracellular [Ca 2+]
Q: How does adrenergic stimulation cause smooth muscle activation? Where does the stim
come from?
A: NE and E from sympathetic stimulation activate 1 adrenergic receptors which activate IP3
which causes release of Ca2+ from SR leading to smooth muscle contraction.
Q: How does adrenergic stimulation cause smooth muscle relaxation? Where does this stim
come from?
A: NE and E from sympathetic stimulation activate 2 adrenergic receptors which activate cAMP
which stimulates PKA to ~P MLCK decreasing Ca2+ sensitivity and increasing SR Ca 2+ pumping
causing relaxation.

Q: What effect does parasympathetic stimulation have on endothelial cells and smooth muscle
cells in the vasculature?
A: Parasympathetic stimulation is a release of Ach. Ach in direct contact with the muscarinic
receptor in a smooth muscle cell causes contraction. Ach (through indirect) is in direct contact
with an endothelial cell and its muscarinic receptor, it causes relaxation through NO which
activates cGMP activates MLC phosphatase causes smooth muscle relxation.
Q: Draw the relationship between Extracellular K+ and the Cardiac RMP. Explain any deviations
from the Nernst equation.
A: Linear relationship except at normal and
hypokalemic situations. This is due to 1) small
Na+ influx and 2) decrease in K+ permeability
(anomalous rectification).
Q: What is Inward (anomalous) rectification?
What purpose does this serve?
A: Decrease in K+ permeability when chem or
electrical driving force is increased (like
membrane depolarization or extracellular K+).
This decreases K+ permeability during the action potential plateau, delaying repolarization
Q: Can the RMP or changes in RMP be determined directly from EKG?
A: No because EKG is an overall view of all the different APs going on in the heart
Q: What effect does hyperkalemia have on membrane K + permeability/concentration gradient/net
effect? Do the same for hypokalemia.
A: Hyperkalemia = increased K+ membrane permeability, decreased [K+] gradient, net effect =
more positive membrane potential (inactivates Na channels). Hypokalemia = decreases K+
membrane permeability (inward rectification), inc [K+] gradient, net effect = little/no change
Q: What is the relationship between each phase (0-5) of the atrial and ventricular muscle APs and
the EKG waveforms?
A:

Phase 0: Na+ channels activate (open). Membrane potential approaches E Na. Phase 1: Na+
channels inactivate (close) and K+ channels (ITO) transiently open. Phase 2: Ca2+ channels activate
(open) and background K+ conductance (IK1) decreases (inward rectification). Phase 3: delayed
activation of K+ channels (IK) and background IK1 conductance increases again (reversal of inward

rectification). Phase 4: background K+ conductance (IK1) high, delayed IK channels closed

(deactivated), Ca2+ channels closed and Na+ channels recover from inactivation but remain closed.
Q: Explain how fast response AP can become a slow response AP. How does this affect AP
conduction?
A: Fast response AP activate both Na and Ca channels during depolarization, if the Na channels
are inactivated (TTX toxin/infarct releases K/Ca inactivating Na channels) then it becomes a
slow reponse because Ca channels are unaffected.
Q: What is the structure of the incalated disk? Its function?
A: Made up of fascia adherens (actin anchoring to sarcomere), macula adherens (desmosome
intermediate filament anchors), and gap junctions (connection for AP to travel b/t cells).
Q: What is the role of gap junctions in cardiac conduction? What ions are they sensitive to?
A: Allow AP to travel between cells, determines internal cell resistance, sensitive to intracellular
[Ca2+] and [H+] ions (Ca and pH).
Q: What is the structure and function of the SA node & AV node? Shape, gap, myofibril
A: Small diameter, tapered, few gap junctions (slow conduction) and few myofibrils (weak
contraction), serves as pacemaker
Q: What is the structure and function of the Atrial and Ventricular muscle? Shape, gap, myofibril
A: Medium diameter, rectangular, abundant gap junctions (fast conduction), abundant myofibrils
(strong contraction), serves as conduction / contraction
Q: What is the structure and function of the His bundle, bundle branches, and Purkinje fibers?
Shape, gap, myofibril
A: Large diameter, cylindrical (very rapid conduction), abundant gap junctions (v. rapid
conduction), few myofibrils (weak contraction), serves as very rapid conduction
Q: What is the relationship between the RMP and Na channel availability? How does that affect
heart conduction? What about in hyperkalemia or MI?
A: Max Na channel availability is -80 to -90mV (normal is -70mV when 80% available) and 0%
at -50mV. Hyperkalemia or MI causes more positive RMP which inactivates more Na channels,
slowing conduction. Also can have premature excitation during relative refractory period which
can cause arrhythmias.
Q: Define P-R interval and QRS interval. What do they tell us about the AV node and ventricular
conduction? Discuss long, slurred
A: P-R interval = conduction time from atria to ventricular muscle. QRS interval = intraventricular conduction time. Long P-R tells problem in AV node as atrial impulse isnt activating
the ventricles. Long or slurred QRS tells that intra-ventricular conduction is slowed (caused by
ischemia, hyperkalemia, ventricular tachycardia)

Q: What is a 1st degree heart block? What is a 2nd degree? What is a 3rd degree?
A: 1st degree = abnormal prolongation in P-R interval >.20 sec. 2nd degree = not all P waves
followed by QRS (some
atrial impulse fail to activate
ventricle). 3rd degree =
complete AV node block, no
consistent P-R interval.

Q: How does parasympathetic (ACh) and sympathetic (NE) nerve activity affect conduction
through AV node? Discuss the interval as well.
A: Ach = muscarinic AChR, activates G-protein which inc K+ permeability hyperpolarizing the
cell, inhibits cAMP synthesis by adenylyl cyclase slowing slow inward Ca 2+ current (slower AV
node conduction), also inhibits atrial contraction, inhibits SA node pacemaker activity, inhibits
AV node conduction = lengthens P-R interval (no effect on ventricle contraction).
NE = affects all heart via 1 adrenergic receptor to increase cAMP, increases slow Ca 2+ current,
increases contraction, increases SA node rate (HR & dec R-R interval), increases AV node
conduction = dec P-R interval.
Q: What are: supraventricular tachycardia, ventricular tachycardia, atrial fibrillation, ventricular
fibrillation? What are their effects on cardiac function/output?
A: Supraventricular tachycardia = normal QRS, rapid atrial contraction, normal stroke volume.
Ventricular tachycardia = abnormal slurred QRS, His-Purkinje not used, stroke vol compromised.
Atrial fibrillation = re-entry of excitation cause, asynchronous atrial contraction, output is
decreased but not life-threatening. Ventricular fibrillation = re-entry of excitation cause, async
ventricular contraction, output is compromised and fatally low.
Q: Define effective (absolute) and relative refractory periods of the heart.
A: Effective (ERP) = channels are completely inactivated, no AP can be elicited. Relative (RRP)
= channels are partially recovered and abnormal AP can be elicited.
Q: What is responsible for ERP and RRP? Discuss what dependence for fast & slow response.

A: Voltage and time dependence of Na+ (fast) & Ca2+ (slow) channels. Na/fast channels are
primarily voltage dependent and Ca/slow channels are primarily time dependent.
Q: What is the ventricular muscle refractory period on EKG?
A: The absolute is the QRS on EKG. The relative is the S-T interval. (Double check this)
Q: What is R on T phenomena? What does it lead to?
A: A premature beat (R wave) that occurs during the relative refractory period (T wave) of the
previous beat. This can precipitate torsades de pointes (polymorphic ventricular tachycardia).
Q: What characteristics of the AV node protect the ventrical from rapid atrial rhythms (A-Fib)?
A: Slow response refractory period is signficantly longer than AV node AP. This means that when
the voltage is fully repolarized the cell is still refractory. This prevents rapid ventricular activation
(particularly important for stuff like A-Fib).
Q: What determines ventricular rate and rhythm during atrial fibrillation? How would you slow
the ventricular rate in a patient with A-Fib?
A: The AV node refractory period determines rate and rhythm. You would give medications that
would lengthen the ERP, you can also shorten to increase the rate.
Q: What is the major risk factor for A-Fib? What is the danger of A-Fib and what would be the
first step to treating it?
A: Age is the major risk factor, the danger is blood clots (stroke/MI/pul embolism) due to pooled
blood in the atria. You would give anticoagulants prior to any other treatment then ablation.
Q: What is the effect of heart rate on AP duration (interval-duration relationship) ? How does it
affect the Q-T interval of the EKG?
A: Increasing HR decreases AP duration (systole). This means a shorter Q-T interval. It also will
shorten the diastole (preload / time between beats) and that will actually be shortened more with
increased HR compared to systole.
Q: What is a prolonged Q-T syndrome? What are potential causes? What can it lead to?
A: It is an abnormal prolongation of the Q-T interval. Either acquired (bradycardia, hypokalemia,
drugs (quinidine)) or congential (genetic lesions in Na or K channels). It can lead to Torsades de
Pointes when the Q-T is abnormally prolongs.
Q: What is the hierarchy of pacemakers in the heart in terms of inherent beating rate? Why?
A: It follows anatomically: SA node > latent atrial pacemakers > AV node / His bundle > bundle
branches > Purkinje fibers. You want the fastest one syncing the rest so thats why SA is fastest.
Q: Explain the cellular/ionic mech for SA node / purkinje fiber pacemaker activity.

A: SA node: 1) T-type current turns on at neg voltage & contributes to depolarization. 2)

hyperpolarization-activated inward current If (funny current leaks Na). 3) Deactivation of K +
current (IK) IK dec means less + leaving, so cell becomes -. 4) Inward Na/Ca exchange current
activated by intracellular SR Ca release sending out Ca brings in a little Na which contribute
to depolarization. Purkinje fiber: primairly due to If current and deactivation of K+ current.
Q: How do changes in threshold potential, the slowing of diastolic depolarization, and maximum
diastolic potential alter pacemaker activity? A graph could help.
A: Make it longer or shorter to reach the
threshold and activate

Q: Define overdrive suppression and its effects on cardiac pacemaker function. When could this
occur (3 things)?
A: When stimulated at higher frequency than intrinsic and then stopped, causes temporary
suppression of all pacemaker activity. Happens with SA node or AV node block, stopping artifical
pacemaker, or sick sinus syndrome (site of pacemaker shifts around)
Q: How does parasympatheic and sympathetic nerve activity regulate heart rate through diastolic
depolarization and maximum diastolic potential? Talk about cellular/ionic mechanisms.
A: Ach/vagus/parasymp: 1) inhibits pacemakers within SA node, atria, and AV node, 2) increases
K+ permeability, 3) decreases cAMP synthesis, 4) Inhibits slow inward L-type Ca 2+ current and If
current by inhibiting cAMP synthesis, 5) decreases slow of diastolic depolarization and
hyperpolarizes maximum diastolic potential. Sympathetic: 1) stims all cardiac pacemakers, 2)
increases slow inward L-type Ca2+ current and If current by cAMP synthesis, 3) Increases slow of
diastolic depolarization.
Q: What is sinus arrhythmia? How do different phases of inspiration affect pacemaker rate?
A: Sinus arrhythmia = normal variability in pacemaker cycle length primarily due to respiratory
changes in parasympathetic (vagal) tone to SA node. Inspiration = decrease in cycle length
(inhibits para), Expiration = increase in cycle length (stims para).
Q: How do changes in SA node pacemaker rate and shifts in pacemaker location manifest on
EKG?

A: SA pacemaker rate manifests in variable heart rate. Ventricular pacemaker will occur without a
P-wave. Junctional pacemaker will have a P wave that is absent or hidden by a QRS complex.
Note that parasympathetic (Vagus) does not impact ventricular contraction, it only decreases heart
rate. Sympathetic both speeds heart rate and increases force of contraction.
Q: Define cardiac arrhythmia
A: A disturbance in the normal electrical activity of the heart due to either 1) impulse formation
or 2) impulse conduction or 3) both.
Q: What are the 3 cellular mechanisms responsible for cardiac dysrhythmia? How can each
mechanism cause cardiac arrhythmia?
A: 1) Altered automaticity = alteration in pacemaker rate, cause problem with impulse formation.
2) Re-entry of excitation = need geometry for conduction loop, slowed conduction, and
unidirectional conduction block to cause (most common cause). 3) Triggered activity = DAD
(tachycardia) or EAD (bradycardia).
Q: What causes altered automaticity?
A: TACHY: NE, stimulants (amphetamines), ischemia, stretching (ventricular anuerysm), sick
sinus syndrome, fever, hyperthyroidism. BRADY: drugs ( blockers, Ca antagonists, antiarrhythmics, digitalis), barbituates, anesthetics, ischemia, sick sinus syndrome, aging (fibrosis).
Q: What causes re-entry of excitation?
A: Ischemia, infarction, congential bypass tracts (Wolf-Parkinson-White = WPW)
Q: What causes Triggered activity?
A: Delayed Afterdepolarization (DAD) = elevated intracellular [Ca2+] from digitalis toxicity,
elevated catecholamines, rapid heart rate or all in combination. Early Afterdepolarizations (EAD)
= acidosis (ischemia), hypokalemia, quinidine (class 1 anti-arrhythmic agent), slow heart rate.
Q: Define bradycardia and tachycardia. When are these rhythms normal or abnormal?
A: Bradycardia <60 beats/min, Tachycardia >100 beats/min. During rest or exercise for athletes
both can be normal, depends on activity. Tachy during rest and brady during exercise is bad.
Q: What are the differences between EAD & DAD of triggered activity? What is the mechanism
for both?
A: EAD is due to abnormal elevated intracellular [Ca 2+] from digitalis toxicity, elevated
catecholamines, rapid heart rate or all in combination. This is due to increated stim frequence
which increases [Ca] in cell which when NAC reduces it imports Na which causes a
depolarization. Early Afterdepolarizations (EAD) = acidosis (ischemia), hypokalemia, quinidine
(class 1 anti-arrhythmic agent), slow heart rate. Uncertain mech but though do be due to
extending the duration of the AP, and it may contribue to prolonged QT syndrome by extending
the AP.

Q: What would each of the following look like on EKG (be able to identify): sinus tachycardia,
sinus bradycardia, 1st/2nd/3rd degree heart block, ventricular tachycardia, A-Fib, and V-Fib?
Q: How do each of the following anti-arrhythmic therapies work: anti-arrhythmic drugs, cardiac
ablation, cardioversion, and implantable defribillator?
A: Anti-arrhythmic drugs are Na/K/Ca channel blockers or blockers. Cardiac ablation uses
radio-frequency waves to destroy the arrhythmic producing myofibers ensuring normal
conduction. Cardioversion is used to mainly treat A-Fib and it restores normal sinus rhythm.
Implantable debrillator measures the heart and shocks it during ventricular fibrillation.
Q: What are the EKG interval values for P-R interval, QRS complex, Q-T interval, tachycardia
cycle length, bradycardia cycle length?
A: P-R interval = .12-.20 sec (120-200 msec). QRS complex = .07-.10 sec (70-100 msec). Q-T
interval = .25-.43 sec (250-430 msec). Tachycardia = cycle length <.6 (600 msec) (>100
beats/min). Bradycardia = cycle length >1.0 sec (1000 msec) (<60 beats/min).
Q: Draw the Cardiac-Excitation complex. Include the mechanism for both depolarization /
contraction and relaxation / repolarization. Understand how an AP leads to contraction though the
molecular mechanism. Start with Ca entering and end with contraction. Discuss Catecholamine
activation mechanism.

A:

Q: What is the role of the Sarcolemma in muscle contraction?

A: Propagation of APs, controls Ca2+ influx into cell by activation of slow inward Ca current.
Q: What does the transverse tubule (T-tubule) do in cardiac cells? What does it line up with?
A: Transmits electrical activity to the cell interior (directly to the SR), located at Z-lines
Q: What is the function of the terminal cisternae and longitudional cisternae in the sarcoplasmic
reticulum?
A: Terminal = where Ca influx triggers opening of Ca release channels to initiate contraction.
Longitudional = site of Ca re-uptake to initiate relaxation.
Q: What is the function of Troponin C?
A: Ca receptor on contactile (actin) protein.
Q: What are the steps of E-C coupling in Cardiac Muscle? Start with AP conducting down Ttubule. How long is contraction maintained? How is Ca removed?

A: 1. AP conducts along membrane and down T-tubule.

2. T-tubule depolarization activates Ca influx via slow inward Ca current
3. Influx of Ca binds to and opens SR Ca release channels (ryanodine receptors)
4. Ca release from SR binds to troponin C to initate cell contraction
5. Ca induced Ca release (CICR)
6. Contraction is maintained as long as cystolic Ca is eleveated
7. Relaxation occurs when cytosolic Ca is removed (80% = SR uptake, 18% NCX, 2% Ca pump)
Q: What is the difference between cardiac and skeletal muscle cells? Cell size, syncytium,
activation method, contraction dependence, contraction amplitude control, summation/tetanus,
metabolism method
A: Cardiac: small cells, syncytium (electrically coupled gap junctions), cell-cell conduction
activation (no NMJ), Ca Induced Ca release, no summation/tetanus, primary aerobic metabolism
Skeletal: fibers can run full length muscle, not electrically coupled, neuro-muscular junctions
(Ach), not Ca influx dependent (voltage sensor of Ca channel), AP frequency & central
recruitment for amplitude, summation/tetanus = max tension, anaerobic metabolism
Q: How do catecholamines (NE/E) affect inotropy? How do they work molecullarly?
A: Positive inotropic agents. Bind to 1-adrenergic recetpors, activates GS to activate adenylate
cyclase, increases cAMP, cAMP activates PKA (protein kinase A). PKA ~P the following: Ca
channels (inc Ca influx) and phospholamban to increase SR Ca uptake (enhance relaxation)
which increases Ca-induced Ca release (inc contraction strength) and decrease relaxation time
Q: How do Cardiac glycosides (e.g. digitalis) affect inotropy? How do they work molecularly?
A: Positive inotropric agents (congestive heart failure). Inhibits Na-K pump which increases
intracellular [Na] decreasing [Na] gradient, this decreases Ca extrusion by NCX and increases
[Ca] intracellular, inc [Ca] means more SR uptake and greater SR release and contraction.
Q: How do Ca channel blockers (verapamil, diltiazem, nifedipine) affect inotropy? SM & cardiac
A: Vasodilators (smooth muscle) and anti-arrhythmic agents (cardiac). Blocks Ca influx via Ca
channels, decreases SR Ca release and SR Ca content less vascular smooth muscle
contraction. Cardiac due to inhibited slow inward Ca current which inhibits AV node AP
conduction but results in negative inotropic effect on heart (weaker contraction).
Q: How does heart rate and rhythm affect force of cardiac contraction? How does this apply to
the radial pulse during A-Fib?
A: The force-frequency relationship shows that faster HR will have a stronger contraction (after
an initial drop off when the SERCA hasnt filled SR enough and not enough Ca available). The
reverse is true for slowing HR where long initial pause allows for more SR fillling by SERCA
and stronger contraction before adjusts and decreases SERCA rate. Can feel this during A-Fib as
there is variable contractility with stronger and weaker contractions that can be felt at radial
pulse.
Q: What is the cellular mech for the contractile response to an increase in heart rate?

A: Positive staircase (treppe) = as HR inc contraction increases. Greater Ca influx and less time
for Ca efflux via NCX. Increased SR [Ca] and SR [Ca] release larger contraction strength
Q: What is the cellular mech for the contractile response to a decrease in heart rate?
A: Negative staricase = as HR decreases contraction strength dec. Less Ca influx and more time
for Ca efflux via NCX. Decreased SR [Ca] and SR [Ca] release smaller contraction strength
Q: What is the cellular mech for the contractile response to a premature beat?
A: Smaller than normal contraction. Less time for recovery of slow inward Ca current, less time
for recovery of SR Ca release channels, less time for Ca SR redistribution to terminal cisternae.
All results in smaller Ca induced Ca release smaller contraction strength
Q: What is the cellular mech for the contractile response to the beat after a premature beat?
A: Stronger than normal contraction. More time for recovery of Ca current, more time for
recovery of SR Ca release channels, more time for Ca SR redistribution to terminal cisternae. All
results in a larger Ca induced Ca release stronger contraction strength
Q: What does the EKG record?
A: EKG records the rate, rhythm and conduction of electrical activity of the heart. It records the
differences in voltage on the surface of the heart which only occur during a wavefront.
Q: What do upward and downward waveforms on the EKG mean?
A: The wavefront vector is moving toward ro away from the electrode
Q: Define heart rate, preload, afterload, and contractility and how each affects cardiac output.
A: Preload = load on muscle before contraction, stretchs muscle & generates pasive tension
(ventricular filling = end-diastolic volume). Afterload = any force that resists muscle shortening
(arterial pressure). Heart rate = rate of heart contraction, determines rate of cardiac output.
Contractility = ability to generate contractile force, determined by intracellular [Ca], independent
of pre and afterload.
Q: How does isometric and isotonic contraction relate to the heart?
A: Isometric = contraction w/o shortening, forceafterload. Isotonic = contraction w/ shortening,
force = afterload. During cardiac cycle, cardiac muscle initially generates isometric tension (until
aortic valve opens) then isotonic-like contractions as blood is pumped out
Q: What is resting (diastolic) and active (systolic) tension and the length-tension relationship of
cardiac muscle? Draw the graph and explain it, including what determines slope
A: Resting (diastolic) tension = tension from passively stretching the muscle due to ventricular
filling (preload). Resting Tension Slope = muscle compliance. Active (systolic) tension = tension
from isometric contraction at particular muscle length (preload). Active Tension Slope =
contractility (dependent on intracellular [Ca]).

Q: How does preload affect isometric muscle tension development?

A: Preload causes muscle stretching which creates an optimal overlap between thick and thin
filaments causes a stronger contraction. Preload also causes an increase in Ca sensitivity of
myofilaments.
Q: What is compliance and how does it affect the shape of the resting tension curve?
A: Compliance = change in volume (length) in relation to change in pressure (tension). V/ P.
Increasing compliance (more stretchy) means lower pressure for given volume (down and right),
dec compliance is higher pressure for given volume (up and left)
Q: What is contractility and how does it affect the slope of the active tension curve?
A: Contracility = ability of actin & myosin to form crossbridges, determined by intracellular [Ca].
Increase in contractility (+ inotropic) shift curve up and to the left, decrease contractility (inotropic) shift curve down and to the right.
Q: Describe and draw Wiggers diagram (cardiac cycle).
A:

Q: Describe the phases of the cardiac cycle with relevance to the valve opening and closing.
A: Atrial systole AV valves close (mitral/tricuspid) Isovolumic contraction Aortic /
Pulmonary (semilunar) valves open Rapid ejection Reduced ejection Aortic / Pulmonary
(semilunar) valves close Isovolumic relaxation AV valves open Rapid ventricular filling
Reduced ventricular filling (diastasis)
Q: What are the mechanisms responsible for A, C, and V waves of venous pulse?

A: A wave = atrial contraction. C wave = ventricular contraction (tricuspid bulging). V wave =

atrial venous filling.

Q: What causes the first, second, third and fourth heart sounds? What is their position in the
cardiac cycle?
A: 1st = AV valve close (Isovolumic contraction). 2nd = Semilunar valve close (Isovolumic
relaxation). 3rd = rapid ventricular filling. 4th = stiff ventricles filling (Atrial systole)
Q: What is pulmonary cardiac wedge pressure?
A: The pressure measured by a pulmonary catheter with balloon in a small pulmonary artery
branch. It tells you about the left atrial pressure indirectly and is useful in dx pulmonary edema
Q: What are systolic and diastolic murmurs in relation to stenosis or insufficiency (regurgitation)
for the mitral, tricuspid, aortic and pulmonic valves?
A: Mitral/Tricuspid stenosis = diastole. Mitral/Tricuspid regurgitiation = systole.
Aortic/Pulmonary stenosis = systole. Aortic/Pulmonary regurgitation = diastole.
Q: What is the difference between physiological and paradoxical splitting of the 2nd heart sound?
What effect does breathing having on these splitting sounds?
A: Physiological splitting S2 = slower conduction down 1 side than the other (right heart failure /
pulmonary HTN) causing the aortic and pulmonic to not close at the same time. Paradoxical split
S2 = caused by a left bundle branch block. Inspiration decreases intrathoracic pressure delaying
the pulmonic valve closure making the paradoxical split more obvious.
Q: Draw a left ventricle pressure-volume diagram. Talk about how changes in the preload,
afterload, and contractiility will affect stroke volume.
A:

Contractility will change the line in the top

left corner, increased contractility will increase the stroke volume (sympathetic input curve), and
decreased will decrease stroke volume
Q: What is systolic heart failure and diastolic heart failure in relation to ventricular contractility
and compliance?
A: Systolic heart failure = decreased ventricular contractility, decreases SV, and lowers the
contractility curve. Diastolic heart failure = decreased ventricular compliance, decreases SV, and
increases the starting pressure while decreasing the volume (bottom right corner goes up and left).

Q: What is venous return, central venous pool, and cardiac output (respect to heart & pheripheral
vasculature)? What happens to the central venous pool with exercise?
A: Venous return = rate blood return to thorax (blood enter central venous pool). Central Venous
pool = volume of right atrium and great veins in thorax. Cardiac output = rate blood leaving
central venous pool. Exercise/increased demands lowers central venous pool volume (inc output)
Q: With a heart failure patients, what would the effects be on CO and central venous pressure?
What would you see on a central line?
A: Heart failure dec CO, increases central venous pressure, retain fluids to compensate pitting
edema.
Q: Draw a vascular function curve (central venous pressure Y vs cardiac output X). Explain the
drop off that occurs at 0 pressure. What would a CO increase do to central venous pressure, and
venous return?
A: Drop off in pressure venous collapse. CO increase decreases central venous pressure which
increases the venous return (closed system).

Q: How
do you boost venous return? Address: venous valves,
skeletal
leg muscles, cardiac suction, cardiac contraction,
sympathetic vein effects, blood volume changes, and respiration.
A: Venous valves allow for unidrectional blood flow and maintain pressure gradient between
peripheral and central venous pools against gravity. Skeletal leg muscles act like pumps to
increase venous return. Cardiac suction is when the heart contracts and then rebounds to its
resting volume which creates venous suction. Cardiac contraction increases pressure on aterial
side which increases venous pressure and return. Increased sympathetic tone will increase
venoconstriction and increase return. Increased blood volume (hydration) will increase venous
return. Repiration reduces intra-thoracic pressure which increases venous return. End effect of all
these is to increase end diastolic volume increases stroke volume Increased Cardiac Output.
Q: What does increased or decreased blood volume (transfusion/hemorrhage) do to the Vascular
function curve? What does this do to the mean circulatory pressure?
A: Increased volume is a parallel shifts up and right, decreased volume is a parallel shift down
and left. This changes the mean circulatory pressure (y-intercept).
Q: What does increased and decreased venous tone do to the vascular function curve?
A: Increased tone = increased venoconstriction same effect as increased volume. Decreased
tone = decreased venoconstriction (or increased veno same effect as decreased volume (same
shifts).
Q: Draw the Cardiac Function curve (CO Y axis vs CVP X). What would sympathetic activity,
inotropic drugs, and heart failure do to this curve? Discuss moderate and severe heart failure.
A: Sympathetic increases CO and increases CVP, inotropic drugs also increase CO & CVP. Heart
failure decreases CO. With moderate heart failure,
kidneys increases fluid retention, increases
preload, increasing CO to compensate for the
decreased contractility. With severe heart failure
the contractility is so poor that very high CVP due
to fluid retention cant compensate for the
decreased CO. This leads to pulmonary congestion
and pitting edema. Understand what this means
graphically.

Q: What is the circulatory and cardiac adjustments hemorrhage? Discuss this with respect to a
cardiac function graph or vascular function graph.
A: With hemorrhage you have venoconstriction which shunts blood to the aterial side and
improves venous return, aterial vasoconstriction to shunt blood to heart and brain (increased total
peripheral resistance), cardiac contractility increases with sympathetic tone (and circulating
catecholamines), and low blood flow in capillaries causes fluid absorption from tissues which
increases blood volume.
L14
Q: Explain Poiseuilles law and how it relates blood flow, pressure gradient, resistance, blood
viscosity, and vessel diameter and length.

A:

F=

( P 1P2 ) r 4
8 L

Blood flow is directly proportional to pressure gradient, and flow

is inversely proportional to resistance. Blood flow is directly proportional to radius to the 4th
power. Blood flow is inversely proportional to vessel length and blood viscosity. Resistance is
directly proportional to vessel length and blood viscosity. Resistance is inversely proportional to
vessel radius to the 4th power.
Q: What is viscosity? How does viscosity change with vessel diameter and hematocrit?
A: Viscosity = internal resistance between adjacent layers of a fluid or (pressure/velocity).
Viscosity = Shear stress / Shear rate (AKA pressure / velocity). With increasing vessel diameter,
viscosity decreases because flow increases due to the increased radius which increases velocity
which decreases viscosity. With increasing hematocrit, viscosity increases (and anemia decrease
viscosity).
Q: Where is velocity the maximum within a vessel? What about the minimum velocity?
A: Axial flow (innermost layer) has the highest velocity. Minimum is at the vessel wall.
Q: What impact would increased erythropoietin (EPO) or increased altitude have on viscosity?
What about anemia or polycythemia?
A: Increased EPO = increased hematocrit = increased viscosity. Anemia = low hematocrit = low
viscosity. Polycythemia = high hematocrit = high viscosity.
Q: How does hematocrit change with vessel diameter? What is axial streaming? What is plasma
skimming? How do these relate to the hematocrit change with vessel diameter?
A: Smaller vessel diameter have lower hematocrit. Axial skimming is the accumulation of RBCs
in the axial laminae (center of vessel). Plasma skimming is smaller vessels have more plasma and
less RBCs due to axial streaming. The increased plasma content causes a decreased hematocrit.
Q: What is the normal hematocrit range?
A: 35-50%

Q: What is hereditary spherocytosis and what does it result in? (Hint: this has to do with vessel
flow)
A: Spherical RBCs that cant change shape when they enter capillaries which results in anemia.
Q: What is laminar and turbulent flow? What does each sound like?
A: Laminar flow is when fluid moves in concentric parallel layers. Turbulent flow is when fluid is
disorderly and is non-laminar. Laminar is silent, turbulent makes noise can can be the result of
murmurs (bruits). Korotkoff sounds (BP sounds) are due to turbulence.
Q: What does turbulence do to the endothelial lining? What can this result in?
A: Turbulence damages endothelial lining, can cause thrombi. Smokers have damaged endothelial
lining and this can also lead to aneurysms.
Q: What is Reynolds number and how do each of its parameters contribute to the development
of trubulent blood flow?
A: The critical number (without units) for the change of tubulent flow to develop (>3000).
Depends on density, tube diameter, velocity, and inversely to viscosity.

NR=

Dv

Q: When you are taking a blood pressure reading, what factor/parameter causes the turbulence?
A:Velocity, as you decrease the diameter, you are increasing the velocity of the blood and causing
the turbulence.
Q: What vessel is most likely to have turbulent blood flow?
A: Root of the aorta because the biggest vessel and most likely to have turbulent blood flow.
Q: What is Bernoullis principle? How does this apply to the circulatory system (arterial & aortic
stenosis)?
A: Bernoulli is in a constant flow system, Total Energy (potential + kinetic) = constant. At an
abrupt decrease in cross sectional area (stenosis), potential energy (pressure) is converted to
kinetic energy (flow). Transmural pressure decreases as the velocity of blood flow increases in a
stenotic area. With arterial stenosis this can lead to collapse, aortic stenosis can cause such high
velocity that it sucks blood out of the coronary arteries causing ischemia.
Q: What is the Laplace relationship? How does wall tension affect the function of dilated hearts,
capillaries, and aneurysms, and ateriole vasoconstriction?
A: Laplace is Wall Tension = (Pressure x Radius) / Wall Thickness. Dilated hearts have a large
radius high wall tension = high afterload, causes more systolic work and higher O 2
consumption to overcome high wall tension. Capillaries have very small radius = low wall
tension, allows them to withstand huge pressures (think caps in feet while jumping) without
rupture. Aneurysms increase the radius which decreases velocity which increases pressure and
also decreases wall thickness. This creates high wall tension which leads to eventual rupture.

Q: How does wall tension and the anatomy of arterioles and precapillary sphincters (large wall
thickness / lumen diameter ratio) regulate vascular resistance?
A: Aterioles have thick walls but small radius (small lumen) = low wall tension which allows for
easy constriction / dilation (shunting of blood).
Q: What is the relationship between blood flow velocity and cross sectional area? What has a
higher cross sectional area, veins or arteries? How does this correspond with holding volume and
vessel compliance? What about capillaries?
A: Large cross sectional area (capillaries) have low velocity. Small cross section area (aorta) have
high velocity. Veins have larger cross sectional area than arteries, with a high compliance = hold
60% of blood volume. Arteries have lower cross sectional area and low compliance = 18% blood
volume. Capillaries have largest cross sectional area = slowest blood flow.
Q: How is resistance in series and parallel additive (think physics) and what does this mean for
the circulatory system?
A: Series = additive resistance. Parallel = reciprocal additive (1/R). Resistance in series for where
blood must flow through (IVC, lungs, aorta) but in parallel through organ systems.
Q: How does the resistance change with exercise, especially with the lungs? Relates to last
question.
A: Lungs (heart and muscles) open up parallel capillaries which lowers resistance to blood flow
increasing the perfusion.
L15
Q: How does the pulse pressure profile change throughout the circulatory system?
A: Pulse pressure widens as further from heart (due to compliance), MAP continously declines,
no pulse pressure in capillaries / veins. Greatest decrease in pulse pressure across arterioles.
Q: Describe the arterial and venous vascular wall (the 3 main layers and their components).
A: Arterial = Tunica intima (subendothelial connective tissue, internal elastic lamina), tunica
media (smooth muscle, external elastic lamina), tunica adventitia (lots connective tissue, smooth
muscle, vasa vasorurura, innervation).
Venous = tunica intima (subendothelial connective tissue, no IEL), tunica media (less smooth
muscle, no EEL), tunica adventitia (well developed connective tissue with some smooth muscle
and vasa vasorum).
Q: Compare arteries vs veins in terms of vessel wall. BAD QUESTION
A: Arteries have more elastic lamina, more smooth muscle, and less connective tissue (adventitia)
Q: What is relative compliance of collagen (connective tissue), elastic lamina, and smooth
muscle?
A: Elastic lamina has highest compliance, smooth muscle has middle, collagen has lowest.

Q: How do the compliance characteristics impact arterial pressures?

A: Arteries have large amounts of elastic lamina in the tunica intima and media which leads to
higher compliance allowing them to generate more arterial pressure without increased heart
pressure.
Q: What is compliance?
A: Compliance

V
P

Q: What are the 3 different types of capillaries? Discuss endothelium, basal lamina and location
in body.
A: Continuous capillaries = continous endothelial cells, no fenestrations, tight junctions,
continous basal lamina, found in muscle and connective tissue. Fenestrated capillary = continuous
endothelial cells with fenestrations (w/wo diaphragms), continous basal lamina, found in kidney
and intestine. Discontinous (sinusoidal) capillaries = discontinous endothelial cells with wide
spaces, discontinous basal lamina, found in liver (proteins), bone marrow (WBC), and spleen
(RBC).
Q: If arteries are lined with endothelial cells, what are veins and lymphatics lined with?
A: TRICK QUESTION, all blood vessels and lymphatics are lined with endothelial cells.
Q: If you have a change in the normal high compliance of the aorta to a low compliance, what
would the effect be on pulse pressure?
A: Pulse pressure would increase, meaning a higher systolic and a lower diastolic.
Q: Why is a higher pulse pressure bad?
A: Larger pulse pressure (due to arteriosclerosis or decreased compliance) causes a higher
afterload on the heart, which increases O2 consumption and leads to congestive heart failure.
Q: What is the windkessel (hydraulic filtering) properties of the aorta? What does this change in
compliance do lead to eventually for the heart and aorta?
A: A high compliance aorta, takes some of the pressure (potential energy) and converts it to
kinetic energy as it recoils after being stretched by systole. This leads to another bump that
maintains constant flow during diastole. A low compliance aorta doesnt stretch as much by
systole leading to reduced or no recoil during diastole. This increases pulse pressure as diastole
drops. The heart compensates for the wider pulse pressure with increased pressure, more O2
consumption. Eventually leads to congestive heart failure, systolic hypertension, cardiac
hypertrophy, aortic dilation, and low exercise tolerance.
Q: What category of vessels are considered resistance vessels and capacitance vessels? Why?

A: Arteries have constant but low compliance through pressure range = resistance vessels. Veins
have high compliance (geometry: flat then snap open) that accomodate large volumes with little
increases in pressure.
Q: What happens to a vein at arterial pressures? When would this be relevant?
A: At high (arterial) pressures, veins have low compliance. Saphenous veins can be used as
coronary bypass graphs.
Q: What is the pressure pulse? What happens to it with changing compliance? How would this be
impacted by a patient with A-Fib?
A: The pressure wave that travels down the aorta / vessel wall. The pressure pulse will increase as
compliance decreases. With A-Fib, time between ventricular contraction is variable with some
contractions stronger and others weaker (due to Ca influx varying, this is the force-frequency
relationship) and you will feel this in theradial pulse as some pulses are stronger than others.
L16
Q: What are the physiological factors that determine mean arterial pressure? (general)
A: Cardiac output (HR x SV) and total peripheral resistance
Q: What are the physical factors that determine mean arterial pressure? (general)
A: Arterial blood volume and arterial compliance (lower compliance as blood volume goes up)
Q: Why do you put the BP cuff on at the same level of the heart?
A: Do this to remove hydrostatic (gravitational force effects) on blood pressure measurement.
Q: What physiological factor primarily impacts systolic pressure? Diastolic pressure?
A: Cardiac output affects systolic pressure and is regulated by ANS. Total peripheral resistance
affects diastolic pressure and is regulated by ANS and local metabolic activity.
Q: What impact does the Baroreceptor reflex have on arterial pressure?
A: Acts via autonomic nervous system to impact cardiac output and peripheral resistance.
Q: What impact does exercise have on arterial pressure? Pulse pressure? MAP?
A: Systolic increases, diastolic constant or decreases. Pulse pressure widens and MAP increases.
Q: What impact would congestive heart failure, infarction, bradycardia, or sepsis have on arterial
pressure? What about hypertension? (Be really basic: inc/dec for these)
A: First list decreases, HTN increases BP.
Q: What type of HTN do young people get? Old people?
A: Young people get diastolic HTN, old people get systolic HTN.

Q: How does arterial compliance affect systolic and diastolic arterial pressure? Talk about this
with the reference of high TPR and low TPR (peripheral resistance) for both high and low
compliance.
A: Arterial compliance is influenced by age, location of measurement, blood volume, sympathetic
tone and pregnanacy. High complicance decreases pulse pressure which with high TPR means
high systolic and diastolic with a narrow range. With low TPR, high compliance will have a
healthy range BP. Low compliance and high TPR will have a huge pulse pressure and a high
Factors Affecting
Total
diastolic. Low compliance
and low TPR
willPeripheral
have a hugeResistance
pulse pressure with a very low diastolic.

Total Peripheral Resistance

Arteriolar radius
Local (intrinsic) control
Myogenic response
Endothelium-mediated
regulation
(EDRF, NO, endothelin)
Local metabolic changes
(O2, CO2, metabolites)

Response to low BP

Blood viscosity

Extrinsic control

Q:
Discuss
the
figures
below
and what
the
factors
are:

Baroreceptor reflex
Hormonal effects
(angiotensin, epinephrine)

Sympathetic activity
(+) general vasoconstriction
(-) general vasodilation

r4 and
anemia /
polyceth

Autonomic Regulation of Blood Pressure

Heart
rate
Heart
Contraction
strength

Stroke
volume

Sympathetic
stimulation

Cardiac
output

Veins

Arterioles

Venoconstriction

Venus
return

Vasoconstriction

Peripheral
resistance

Blood
pressure

Parasympathetic
stimulation

Heart

Heart
rate

Cardiac
output

Q: How does exercise affect the heart? (heart rate, stroke volume, and cardiac output)
A: Exercise increases sympathetic stimulation to heart which increases heart rate, increases
contractility which increases stroke volume. But as reach maximal HR the SV declines due to
reduced filling time. Cardiac output increases as exercise / HR / SV increase.
Q: How does exercise affect Arterial Pressure and Total Peripheral Resistance?
A: Exercise increases systolic pressure (widening pulse pressure transiently) while diastolic
remains constant or declines at very high workload due to local vasodilation. Total peripheral
resistance declines as blood is shunted from GI/Renal (50%) to skeletal muscle which is under
local control and vasodilates parallel (drops resistance).
Q: How does exercise affect O2 consumption? Detail hemoglobin.
A: Hemoglobin shifted right = more O2 available for muscle, held less tightly. Increased
arteriovenous O2 difference (muscle pulls more O2, less O2 in venous). O2 consumption
increases.
Q: Can the heart vasodilate during exercise? How does this correspond with old people lifting
weights?
A: The heart cant vasodilate. It is a Flow-limited organ, the only way to increase O2 supply is by
increasing flow. When you lift weights you dont have the same sympathetic stimulation which
drops the TPR because you only exercise a limited muscle group. The heart needs more O2 but
TPR is still high, not vasodilating, afterload is high and this leads to ischemia as the heart cant
vasodilate more and get the O2 it needs.

Q: How does exercise affect venous return?

A: Sympathetic venoconstriction decreases compliance shunting blood to heart (inc venous
return). Muscles pump via 1 way valves. Respiratory pump and neg intrathroacic / positive intraabdominal pressure increaes return.
Q: How does exercise affect arterial pressure?
A: Systolic increased due to increased stroke volume (CO) and sympathetic vasoconstriction
contributes to maintaining and raising mean arterial pressure. Diastolic pressure is determined by
TPR and depending on exercise level diastolic increases (low exercise), is unchanged (most
exercise) or decreases (very high exercise). In essence: pulse pressure widens.
L17
Q: What is the basic arrangement of microcirculation including precapillary resistors, metaarterioles, capillaries, and post capillary resistors?
A: Starts at the primary resistors (arteriores, metaarterioles (shunt), precapillary sphincter) then
flows into the capillaries (no smooth muscle) where exchange occurs, then flows into postcapillary resistors (venules)
Q: What are the characteristics of capillary blood flow in terms of precapillary sphincter control,
vasomotion, and Rouleaux formation?
A: It is low velocity that is gradient dependent that has intermittent flow (vasomotion) and is not
uniform. The RBCs are in Rouleaux formation (they stack) which doesnt happen in sickle cell.
Q: When else can Rouleaux formation occur?
A: High protein plasma conditions: myeloma, cancer, and inflammation.
Q: What are the primary determinants (4) of transcapillary fluid (TCF) exchange in terms of
interstitial and plasma hydrostatic and oncotic pressures?
A: Plasma oncotic pressure = exerted by substances (plasma proteins) in the plasma. Tissue
oncotic pressure = osmotic pressure by dissolved interstitum substances (proteins). Capillary
hydrostatic pressure = mean capillary blood pressure. Interstitial hydrostatic pressure = water
pressure from interstitium fluid volume. Usually plasma oncotic pressure is high because more
proteins in capillary and capillary hydrostatic is high because more fluid in the vessel. This leads
to oncotic pulling into capillary and hydrostatic pushing out.
Q: Where is TCF filtering out all the time? Where is it reabsorbing all the time?
A: Glomerulus (kidney) is constantly filtering due to higher arterial pressure of 80 (compared to
32 normally). Lung and right venricle are reabsorbing all the time because lower pressure of 25.
If you dont then you get pulmonary edema.
Q: What plasma protein is the most clinically relevant and does the largest contribution of plasma
oncotic pressure?
A: Albumin which is positively charged, attracts Cl- which brings Na+ which brings H2O.

Q: What happens with TCF exchange in hemorrhage? Nephrosis? Liver damage? (pretty basic)
A: Hemorrhage decreases blood volume, which lowers hydrostatic pressure resulting in fluid
uptake from the tissues. Nephrosis leads to protein loss through urine which lowers plasma
oncotic pressure causing edema. Liver damage (cirrhosis) causes decreased plasma protein
production (albumin) which lowers plasma oncotic pressure casuing edema.
Q: What happens with TCF exhange in portal hypertension? Congestive heart failure? Burns?
A: Portal hypertension increases BP at the hepatic capillary bed causing increased edema leading
to ascites (fluid in peritoneum) and caput medusae. Congestive heart failure is when the left
ventricle fails and backs up the LA which backs up the pulmonary veins which causes pulmonary
edema as the fluid floods into the alveoli. Burns damage the capillaries, increasing their
permeability (and lymphatics), increasing the interstitial fluid and causing edema.
Q: What is pre/post capillary resistance? What the impact of arterial & venous pressure changes
on the hydrostatic pressure in both normal and abnormal (HTN) conditions?
A: Pre/post capillary resistance is the difference between the resistance by pre-cap resistance
vessels (arterioles/metaarterioles/precap sphincter) and the resistance by post-cap resistance
vessels (venules). Arterial pressure has a small efect on cap hydrostatic pressure because the precap resistance is already so high. Venous pressure has a large effect because post-cap resistance is
so low. In normal fluid flows out to the tissues due to higher arteriole pressure. In HTN situations
where venous is higher there is back up into the capillary bed that isnt restricted edema.
Q: Does prostacyclins cause vasodilation or vasoconstriction? How?
A: Prostacyclins inc cAMP ~P of MLCK inhibiting it which leads to inhibited smooth muscle and
vasodilation.
Q: Does Nitric Oxide (NO) cause vasodilation or vasoconstriction? How?
A: NO increases cGMP/PKG to ~P MLCK inhibiting it, causes activation of MLC phosphatase
smooth muscle relaxation vasodilation.
Q: Does EDRF cause vasodilation or vasoconstriction? How?
A: Endothelium-Derived Relaxing Factor is believed to have NO which increases cGMP
activating MLK phosphatase smooth muscle relaxation vasodilation.
Q: Does endothelin cause vasodilation or vasoconstriction? How?
A: Endothelin binds to endothelin receptors on vascular smooth muscle activating phospholipase
C (PLC) to release IP3 which releases intracellular Ca2+ causing smooth muscle contraction and
vasoconstriction.
Q: Do metabolites (adenosine, H+, CO2, K+) cause vasodilation or vasoconstriction? (yes/no)
A: Metabolites cause relaxation and vasodilation.

Q: What is the structure of the lymphatic system (of the vessels)? How does it function with the
circulatory system? What does it depend on to increase / decrease volume and flow?
A: It is the collection and unidrectional return of interstitial fluid (plasma) and protein back to the
heart. It has valves but has thinner walls than veins. Non-fenestrated endothelium, little / no basal
lamina, no smooth muscle. Dumps into the subclavians. The amount of capillary filtration
determines volume, skeletal muscles pump and unidirectional valves help.
Q: What is edema and what conditions predispose edema? Think both physical and patholical.
A: Edema is the accumulation of excess fluid in the interstitial space. Reduced plasma protein
concentration (albumin <2.5 g/dl), increased capillary hydrostatic pressure, increased capillary
membrane permeability, or lymphatic obstruction (parasites) predispose edema. Congestive heart
failure, obstruction of venous return (inc post-cap pressure), renal disease (protein loss), liver
disease (low protein/albumin production), and burns (damaged vessels) cause edema.
L18
Q: What is basal arterial tone? What is resting sympathetic tone?
A: Basal tone = theoretical reference point of constriction without neural or hormonal influence.
Resting sympathetic tone = vascular constriction due to tonic sympathetic nerve activity.
Resistance is higher than basal arterial tone due to tonic NE release.
Q: What is passive / active vasoconstriction and vasodilation?
A: Active mechanisms cause a resistance change away from basal level. Passive mechanisms are
a change toward basal tone. Vasoconstriction will actively increase and passively decrease.
Vasodilation will actively decrease resistance and passively increase resisitance.
Q: Does sympathetic cholinergic influence increase or decrease resistance? Does sympathetic
adrenergic influence increase or decrease resistance?
A: Cholinergic decreases resistance (vasodilation). Adrenergic increases resistance (constriction).
Q: How do alpha-1 adrenergic receptors mediate regulation of vascular tone? Heart and brain?
A: Alpha-1 are in vascular smooth muscle, cause vasoconstriction. Coronary and cerebral vessels
have very little sympathetic vasoconstrictor innervation.
Q: How do beta-1 adrenergic receptors mediate regulation of cardiac tone? How does that
actually work?
A: Beta-1 are the primary adrenergic receptors in cardiac muscle, they stimulate HR and
contractility. Increases cAMP (remember from earlier in the class).
Q: How do beta-2 adrenergic receptors mediate regulation of cardiac tone?
A: Beta-2 are the secondary adrenergic receptors in cardiac muscle, they stimulate HR and
contractility. Their upregulation may be a factor in heart disease (currently being researched).
Also causes gluco-neo-genesis in the liver which increases blood glucose levels.
Q: How do beta-2 adrenergic receptors mediate regulation of vascular tone? Lungs?

A: Beta-2 receptors are primarily located on vascular smooth muscle and casue vasodilation.
They are also found in the lungs and function as bronchiodilators.
Q: Explain the baroreceptor reflex. Describe the receptors and where they run then what it causes.
A: Nerve receptors (mechanoreceptors) in the cardiac sinus and aortic arch measure vascular
stretch induced by changes in blood pressure. Low BP causes a lower frequency (there is tonic
stim) of stimulation on CN IX afferent fibers which go to medullary vasomotor centers. Low BP
causes increase response, increase peripheral vasoconstriction (inc TPR, inc diastolic), increase
heart rate (+ symp, - para), increase ventricular contractility (+symp). High BP does the opposite,
decreases vasoconstriction, decreases HR (-symp, + para), decreases contractility (- symp).
Q: What type of feedback loop is the baroreceptor reflex? What receptor is more sensitive, carotid
or aortic arch?
A: Negative feedback loop. Carotid body is more sensitive. Aortic arch mainly responds to
increased BP
Q: What type of pressure changes are baroreceptors most sensitive to? What happens with
hypertension to baroreceptor sensistivity?
A: Baroreceptors are more sensitive to pulsatile (phasic) pressure compared to constant (static)
pressures. With hyptension, the baroreceptor is less sensitive and needs larger changes in pressure
to increase / decrease sympathetic tone.
Q: What happens to the baroreceptor and sympathetic tone if you dampen the pulse pressure but
keep the MAP constant?
A: Decreased baroreceptor firing and increased sympathetic tone (increased arterial pressure due
to vasoconstriction).
Q: What is the anatomy of peripheral chemoreceptors? How are they activated? She thinks the
graph is important
A: They are small, highly vascularized bodies in the aortic arch and medial to carotic sinus.
Measure PO2 and are activated by low arterial PO2 but also high arterial PCO2 and low arterial
pH. They regulate respiration rate and low O2 increases respiration. They are only activated in
severe hypoxia (not normal PO2 fluctuations).
Q: What is the chemoreceptor reflex pathway? How does it work in theory, and in reality? I dont
know about this question / picture.
A: Receptors afferent in on CN IX for carotid and X for aortic and out on CN X to heart. They
stimulate the medullary vagal center to decrease HR through parasymp or decreased sympathetic
as well as increasing respiratory activity which reduces hypocapnia and increases lung stretch.
Both of those inhibit the medullary vagal center. In theory: stimulates ANS to cause
vasoconstriction and bradycardia. In reality: hypoxia causes tachycardia because increased
ventilation acts via stretch receptors in lung to inhibit vagal stim (tachycardia).
Q: What efffect does high PCO2 have on peripheral chemoreceptor?

A: High PCO2 causes the peripheral chemoreceptor to be more sensitive to PO 2 which leads to
more response at a higher PO2 than it would otherwise.
Q: What is the renin-angiotensin-aldosterone mechanism for blood volume regulation? When
does this kick in? Draw the flow chart to make sure you understand it.
A: Kicks in with dehydration to mitigate its effects.
Hypovolemia stims
baroreceptor which increase
afferent renal arteriole to
release RENIN which takes
angiotensinogen to
angiotensin I which is taken
to angiotensin II by ACE
which acts on hypothalamus
for thirst and ADH,
aldosterone release from
adrenal cortex, increases Na
reabsorption,
vasoconstriction of renal
and system vessels to
increase fluid volume and
BP.

L19
Q: What is autoregulation? What is autoregulation for?
A: Autoregulation maintains constant blood flow in spite of gravitational forces. Autoregulation
can be changed, it is there for resting conditions.
Q: How does autoregulation keep the flow constant? (keep this basic) Does it work at all
pressures?
A: It increases arterial resistance as arterial pressure increases. It only works within a range and
fails at very high and very low pressures.
Q: What is the myogenic hypothesis of autoregulation? What happens with an increase / decrease
in pressure?
A: Vascular smooth muscle contracts in response to stretch and relaxes in response to stretch
reduction. Pressure increases causes increased initial flow which causes a vessel wall stretch
which leads to vascular smooth muscle contraction causing vasoconstrction and an increase in
resistance (which drops blood flow). Pressure decrease causes reduced stretch due to less flow,
causing vascular smooth muscle relaxation and vasodilation leading to resistance drop and blood
flow increase.

Q: What is the metabolic hypothesis of autoregualtion? What happens with an increase / decrease
in pressure?
A: Metabolic activity produces metabolites like adenosine, H+, CO2, that relax smooth muscle.
Pressure increase causes initial flood of blood flow that washes out inhibitory (vasodilating)
metabolites leading to resistance vessel constriction (vasoconstriction), increasing resistance and
decreasing flow. Pressure decrease causes metabolite build-up which leads to vasodilation,
decreasing resistance and increasing flow.
Q: What types of tissues have strong autoregulation? IMPORTANT
A: Heart, brain, kidney, skeletal muscle.
Q: What tissues have little autoregulation? IMPORTANT
A: Skin and lungs
Q: What tissues have weak autoregulation? IMPORTANT
A: Splanchnic circulation (GI organs, pancreas, spleen, liver).
Q: Is autoregulation dependent on endothelial cells?
A: No, autoregulation is not dependent on endothelial cells. It is a property of smooth muscles.
Q: What is the endothelial-mediated mechanism for regulating blood flow? When does this
happen?
A: Local blood flow increases metabolic production of NO or EDRF due to the increased shear
stress caused by the increased flow. This leads to vasodilation and further increase of blood flow.
Summary: increased blood flow directly releases NO/EDRF/prostacyclins that directly further
increase blood flow. This happens during exercise.
Q: What are endothelium-derived vasodilator agents? What are endothelium-derived
vasoconstrictor agents?
A: Vasodilator = Prostacyclins, NO, EDRF. Vasoconstrictor = Endothelin.
Q: How does metabolic regulation for regulating blood flow work? (its pretty basic)
A: Metabolites are released that act as local vasodilators that increase blood flow to the tissues.
This is espeically important in skeletal muscle, cardiac muscle and brain. Also an Oxygen
reduction can cause metabolite formation that leads to vasodilation.
Q: What happens with active (functional) hyperemia in relation to blood flow?
A: Active (functional) hyperemia happens with active tissues that causes increased blood flow
due to the metabolites (K+, inorganic phosphate, interstitial osmolarity).
Q: What happens with reactive (passive) hyperemia in relation to blood flow? How does this
correspond with angioplasty? How about compartment syndrome?

A: Transient increase in blood flow following brief arterial occlusion. The metabolic debt
increases the blood flow in a corresponding level to the blockage duration (overshoots).
Compartment syndrome can also cause damage when flow resumes.
Q: How does mechanical (tissue pressure) regulate blood flow? What are possible causes? Think
heart, skeletal mucscle, lungs, tumors.
A: Mechanical pressure compresses and alters blood flow through small vessels. Muscle
contraction: skeletal muscle (isometric contraction blockage causes ischemia which hurts
think wall squats), cardiac muscle (systole occluses vessels, with aortic stenosis and increased
afterload cuts off flow to endocardial surface). Alveolar pressure (lungs expansion
resists/changes blood flow). Tumors (compress veins first due to low pressure).
Q: What happens in cardiogenic shock? What are some causes (3)?
A: Heart muscle damage (severe MI), cant pump enough blood to meet body needs.
Dysrhythmias like V-tach and bradycardia by complete heart block can cause. Cardiac tampanode
can prevent full filling / expansion.
Q: What happens in hypovolumic shock? What can cause this?
A: Cant supply enough blood to body due to too much blood / volume loss (10-20%). Aka
hemorrhagic shock. Can be caused by dehydration, burns, vomiting, diarrhea.
Q: What happens in anaphylatic shock?
A: Sudden, severe, systemic allergic reaction. Causes airway obstruction or extreme hypotension
due to all the capillary beds opening. Caused by food, medication, insect stings, latex (medical).
Q: What happens in septic shock?
A: Immune response to severe infection and sepsis. Results in massive vasodilation, increased
capillary permeability, decreases systemic vascular resistance, and hypotension leading to tissue
hypoxia.
Q: What happens in neurogenic shock?
A: Sudden cut off of ANS control signals that control vasoconstriction hypothension. Happens
after acute spinal cord injury that blocks sympathetic activity.
L20
Q: What is coronary dominance? What are the percentages? (they wont ask us but boards will)
A: Determined by supply of PDA. Right dom = 50%, Left dom = 20%, Co-dom = 30%.
Q: What is the capillary to myocyte ratio? Capillary to myofiber? Are they all active always?
A: 1:1 cap to myocyte, 3-4:1 cap to myofiber, not always active, all active in ischemia.
Q: What is the primary determinant of coronary blood flow? What regulates it?

A: Aortic pressure is primary determinant of coronary blood flow. Metabolic activity and
arteriolar resistance regulates coronary blood flow.
Q: Does the left ventricle pressure influence more: right coronary blood flow or left coronary
blood flow?
A: Left coronary blood flow.
Q: When does the majority of coronary blood perfusion to the LV occur? How could this be
problematic with hypotension?
A: During diastole, especially early diastole when the LV tissue pressure drops so low. With very
low diastole, the heart may not be perfused enough MI.
Q: In normal conditions, what happens with blood flow to the endocardial and epicardial
surfaces? What would happen in abnormal conditions like aortic valve stensis, regurgitation, or
congestive heart failure? (discuss pressures) Which surface is more at risk for ischemia?
A: Normal conditions: endocardial will normally be more dilated to handle the increased
pressures (and inc compression) they have during ventricular diastole. Abnormal conditions lead
to greater ventricular diastolic pressures which compresses more and reduces coronary blood
flow. Thic can lead to subendocardial ischemia. Endocardial is more at risk for ischemia.
Q: What happens to endocardial and epicardial blood flow during diastolic coronary hypotension?
What could cause diastolic coronary hypotension?
A: Endocardial will be more reduced than epicardial and is at increased risk for ischemia (endo
has more pressure than epi which restricts blood flow). Severe hypotension or partial coronary
occlusion.
Q: What is more important neural or metabolic regulation for coronary blood flow? What effect
do 1 adrenergic receptors have on coronaries? What cells are influenced by 1 adrenergic
receptors in the heart? What is the effect? What cells are influenced by 2 adrenergic receptors in
the heart? What is the effect?
A: Metabolic is much stronger than neural (vagus) regulation. Alpha-1: sympathetic
vasoconstriction on the coronaries. Beta-1: pacemaker cells and myocardium, overriding strong
coronary vasodilation due to metabolism increases. Beta-2: coronary smooth muscle, mediates
vasodilation but less sensitive to NE stimulation.
Q: What is the major factor in regulation of coronary blood flow? What order relationship is this?
How can this balance lead to ischemia? SHE HAD A STAR ON THIS SLIDE
A: Metabolism is the major factor in regulation, linear relationship between coronary blood flow
and myocardial metabolic activity. O2 supply is flow limited becauses extracts 80% of O2 from
blood through passage. If heart needs more O2, it needs more flow. In a diseased heart the flow is
already limited and increased demand can lead to ischemia.
Q: What are the metabolic substrates (sources) for the heart?
A: 1. Fatty acids (60%), 2. Carbohydrates (35-40%), 3. Others. High fat burn means high O2 burn

Q: What is the formula for Cardiac work? What does this mean clinically? What is pressure work
and volume work? Which one uses more O2? What does this mean for hypertension?
A: Cardiac work = Mean arterial pressure X systolic stroke volume. This tells you about
myocardial O2 consumption. Pressure work is higher arterial pressure and lower SV. Volume work
is lower arterial pressure and higher SV. Pressure work consumes much more O 2 than volume
work. Hypertension causes disproportionate increase in O 2 consumption.
Q: Why is pressure work greater than volume work?
A: Pressure work is more isometric contraction which uses up ATP rapidly in crossbridge
formation. This is why the O2 demands / greater work with pressure work.
Q: What factors influence myocardial oxygen supply? Demand? How do these balance?
A: O2 supply = myocardial blood flow X arterial O2 content. Myocardial blood flow is influenced
by diastolic perfusion pressure and coronary vascular resistance. O2 demand = afterload, HR,
contractility. Cardiology is about giving Beta blockers to decrease contractility, and controlling
HTN to limit the demand to allow the disease-limited supply to meet it.
Q: What is the primary cause of ischemia, excessive O 2 demand or insufficient O2 supply?
A: Insufficent O2 supply is the primary cause. Think of disease limiting supply.
Q: Is collateral circulation enough to prevent sudden infarction? What are they sufficient to aid?
Why would they recommend moderate exercise for mild heart attack patients?
A: Insufficent for sudden infarction. Sufficient for gradiual obstruction, can protect some. For
mild heart attacks, moderate exercise increases angiogenesis inc collateral circulation.
Q: How does coronary steal work? Use an example of 2 coronary beds with one having a
atherosclerotic plaque that impedes flow. How does this lead to ischemia?
A: Plaques in coronary bed 1, causes maximal arterial dilation in normal resting conditions.
Coronary bed 2 is relatively vasoconstricted. With exercise or administered vasodilation, flow to
bed 2 is increased due to vasodilaiton and lowered resistance. This steals blood flow from bed 1
because that is already max vasodilated and the steal of flow leads to severe ischemia in 1.
Q: When does coronary steal happens clinically?
A: Exercise-induced ischemia. Stress-testing (adenosine). Peripheral Arterial Disease (PAD) =
claudication after walking a short distance. Pain relieved after rest. This causes fibrosis of the
skeletal muscle over the long term. PAD is coronary steal in the peripheries.
Q: What is the general features of skeletal muscle circulation? Address flow during rest and
exercise, size of the vascular bed relative to the body, and ability to increase with exercise, tonic
vs phasic muscle blood supply.
A: 20% of CO goes to skeletal muscle (40% of body mass), largest vascular bed in body, low
flow at rest, can increase 20x with exercise, tonic gets 5x phasic lood supply.

Q: What are the metabolic controls for skeletal muscle? How does it vary with rest and active
hyperemia? What is its flow reserve/capacity? What does that mean for vascular tone?
A: Active hyperemia is increase in flow due to metabolic activity. Whole body exercies cause
80% of CO to go to contracting muscles. Skeletal muscle has very high flow reserve because at
rest it is so low. Skeletal muscle has a high vascular tone. Rest = vasocontriction dominates,
Active = vasodilation dominates to deliver O2 and remove metabolic waste.
Q: What are mechanical factors that control skeletal muscle circulation? What is the overall
effect? Discuss the difference between dynamic and isometric exercise on arterial circulation.
A: Muscle contraction compresses vessels. Dynamic / rhythmic exercise alternates constriction
and free flow but the overall effect is decrease in resistance due to metabolic vasodilation. With
Isometric exercise there is very little blood flow, vascular resistance increases and CO rises,
which raises arterial pressure.
Q: What are the effects of skeletal muscles on venous circulation?
A: Muscle contraction pumps blood out. Respiration increases venous return during inspiration.
Sympathetic venoconstriction increases tone and decreases capacitance which increases venous
return.
Q: What are the neurohumoral mechanisms for skeletal muscle circulation control? How does it
impact with rest, anticipation of exerecise and during exercise? Discuss alpha adrenergics,
sympathetic cholinergics, beta adrenergics, acetylcholine, epinephrine (both low and high
concentrations) and norepinephrine.
A: NE affects alpha-adrenergic receptors for vasoconstriction during rest. This gives a large
portion of vascular tone. Sympathetic cholinergics release Ach vasodilation through
muscarinics on endothelial cells which leads to NO production. This happens during anticipation
of exercise and during exercise to increase blood flow. Adrenal medulla releases epinephrine
which activates Beta-2 adrenergic receptors on vessels at low concentration. At higher
concentrations, epinephrine causes vasoconstriction through Alpha adrenergic receptors.
L21
Q: What are the general characteristics of cerebral circulation address: % of CO at rest,
metabolism demands, ranking of metabolic activity, lymphatics, tolerance to blood supply
interruption, blood-brain-barrier molecule permeability?
A: Brain receives 15% of resting CO, aerobic glycolysis = needs steady arterial O 2 and glucose,
Most metabolically active, Little lymphatics = bad edema, Intolerant to interruption: 5 sec =
unconscious, minutes = death, BBB permeabile to small lipid soluble (O2, CO2, ethanol,
steroids) and specifically transported (amino acids, glucose). Problem for drug permeability.
Q: How does autoregulation affect cerebral blood flow? What does flow rate depend on? What is
the usual Cerebral Profusion Pressure (CPP)? What does an increase / decrease mean? What is the
adjustment to hypertension?
A: Maintains consistent blood flow, flow rate depends on neural activity. CPP usually 80-100
mmHg. Dec CPP = cerebral vasodilation, inc CPP = cerebral vasoconstrction. With HTN,

autoregulation is shifted right to maintain constant @ higher pressure but less well regulates
lower arterial pressure.
Q: What is the formula for CPP? What would shock or a brain tumor do to CPP?
A: CPP = mean arterial pressure intracranial venous pressure. Shock or any hypotensive that
decreases MAP Decreased CPP. Tumor, hematoma, hydrocephalus or any increase in
intracranial pressure Decreased CPP because increased intracranial venous pressure.
Q: CSF pressure is increasing, discuss the efects on vascular resistance, cerebral venous pressure,
cerebral blood flow, and metabolism mediated effect as CSF pressure climbs. IMPORTANT
A: Initial increase causes increased vascular resistance which decreases cerebral blood flow.
Autoregulation responds to decreased flow with metabolism mediated vasodilation. Past the
autoregulation range (~100 mmHg) near arterial pressure, cerebral blood flow rapidly decreases.
Q: What is the formula for the Monro-Kellie Doctrine? How does that related to cerebral blood
flow? What about when there is an intracranial hemorrhage?
A: Brain Volume + Cerebral Vascular Volume + CSF Volume = Constant. As one compartment
increases, others must correspondingly decrease to compensate. Hemorrhage increases brain
volume = dec vascular & CSF volume, inc vascular / CSF pressure = crushed brain.
Q: How does CO2 affect cerebral blood flow? Keep in mind the BBB. What type of
acidosis/alkalosis has more impact on the brain metabolic or respiratory?
A: Very sensitive to PCO2. CO2 effects H+ which impacts pH. pH = vasodilation, blood flow.
pH = vasodilation, blood flow. Metabolic inc / dec pH directly, Respiratory inc/dec CO 2
directly which crosses BBB greater impact on brain (7% CO2 inhalation doubles cerebral flow)
Q: What would the effect of hyperventilation be on cerebral blood flow? What is the clinical
application of this? (hint: ventilator)
A: Hyperventilation dec CO2, raises pH, causing vasoconstriction, results in dizziness / fainting.
Artificial ventilation causing hyperventilation will decrease flow and decrease vascular volume
thereby reducing cerebral edema formation and cranial pressure at the trade off of decreased
blood flow to the brain.
Q: How does O2 affect cerebral blood flow? What is a scientific application of this?
A: PO2 decreases may cause cerebral vasodilation but less so than CO 2 changes. Useful for fMRI
as you can determine oxygenated vs deoxygenated blood flow within brain to determine
metabolic activity and therefore neural activity.
Q: How does adenosine affect cerebral blood flow? She doesnt care about mech, just overall
A: Adenosine is an immediate metabolite to ischemia. Acts on purinergic receptors on vascular
smooth muscle to activate ATP-sensitive K current hyperpolarization turns off Ca current
smooth muscle relaxation due to low intracellular Ca. MAIN PLAYER

Q: How does K+ ions affect cerebral blood flow? What cells uptake K+ and stabilize extracellular
K+? She doesnt care about mech, just overall effect.
A: K+ comes from active nerves. Causes vascular smooth muscle hyperpolarization/vasodilation.
Astrocytes take up K+ and stabilize extracellular K+ in the brain.
Q: How does Nitric Oxide affect cerebral blood flow? She doesnt care about mech, just overall
A: NO can be released by cerebral endothelium, neurons and glial cells. NO relaxes vascular
smooth muscle by cGMP PKG ~P of MLCK relax dilation SECONDARY PLAYER
Q: How does neural activity affect cerebral blood flow? How big is this effect.
A: Parasympathetic: division of facial impacts some cerebral vessels causing moderate
vasodilation. Sympathetic does minimal vasoconstriction & inc vascular resistance but this is
very weak. Very weak overall effect even from baroreceptors. Local metabolic has primarily
effect.
Q: What is Cushing Response / Reflex? How does it work? VERY IMPORTANT
A: Response to cerebral ischemia due to inc intracranial pressure & decreased cerebral perfusion.
Ischemia stimulates medulla vasomotor centers (solitary nucleus) to inc sympathetic activity
inc systemic BP. Also activates parasympathetic activity dec heart rate.
Q: What is the general anatomy of the pulmonary circulation? What are the 2 circuits? What are
the basic pressures?
A: 2 systems: pulmonary and bronchial (systemic) circulations. Pulmonary gets 100% CO,
Bronchial gets <1% CO. Pulmonary arteries have 7x compliance due to little smooth muscle.
Pulmonary circulation is low pressure, low resistance, high flow. Pressure gradient is 6mm Hg
(pulm art press = 14, mean LA press = 8).
Q: What is unique about pulmonary arteries & pulmonary capillaries? What determines vascular
resistance, how does resistance vary with pressure and flow increases / decreases?
A: Pulmonary capillaries are in the alveolar walls forming an unbroken sheet flow between air
spaces. Pulmonary capillaries have major influence on vascular resistance (40%). Increasing
pressure / decreasing resistance = dec pulmonary resistance due to recruitment of new vessels
(pop open).
Q: Describe the mechanism for the autoregulation of pulmonary vessels.
A: TRICK QUESTION, pulmonary vessels do not autoregulate.
Q: What happens to to alveolar and extra-alveolar vessels during inspiration? During exspiration?
A: Inspiration: negative pressure distends extra-alveolar vessels = slight dec resistance, alveoli
inflation compresses & elongates alveolar microvessels = slight inc resistance. Net effect = slight
increase / no change in pulmonary peripheral resistance. Expiration: positive pressure
compresses extra-alveolar vessels = slight inc resistance, alveoli deflation distends & shortens
alveolar microvessels = slight inc resistance. Net effect = slight decrease / no change in resistance

Q: How does hydrostatic (gravitational) pressure influence pulmonary blood flow? How does this
impact pathological ascultation?
A: Upright person has increased intravascular pressure at the bottom of lung compared to top due
to gravity. Therefore hear rales at bottom of lung due to greater hydrostatic pressure.
Q: What is the vascular waterfall effect on pulmonary blood flow? Discuss the pressure
differences between arterial/alveolar/venous pressures in all 3 zones.
A: 3 zones determined by relationship between arterial (Pa), alveolar (PA), and venous (Pv)
pressures. Zone 1: PA > Pa > Pv, normally doesnt exist but can w/ hypotension or positive
mechanical ventilation. PA is greatest, so collapsed capillaries no O2 transfer. Zone 2:
Pa>PA>Pv, alveolar exceeds venous but not arterial so capillaries partially collapsed and flow
dependent on pressure differences. Independent of the venous pressure. Usually upper third of the
lung. Zone 3: Pa>Pv>PA, as both are greater than PA, flow depends on the arterial/venous
pressure gradient. There is blood flow.
L22
Q: Whats the primary function of cutaneous circulation?
A: Maintain constant body temperature through convective heat exchange. Skin flow exceeds
nutritional requirements.
Q: What is the main regulary control for cutaneous blood flow?
A: Neural is more important than local metabolic control.
Q: Is skin better at promoting or preventing heat loss?
A: More efficient at heat loss where flow up to 30x inc, less efficient at prevention where only
10x reduction. Humans better acclimatizing to heat than cold.
Q: What are the characteristics of apical and non-apical skin in terms of blood flow? What are the
anatomical differences? What are the functional differences?
A: Apical (nose, lips, ears, fingers, hands, feet): high surface-to-volume ratio favors heat loss,
glomus bodies (specialized arteriovenous anastamoses) facilitate heat loss. AV anatasmoses are
shunts under exclusive sympathetic neural control (no metabolic control / autoreg / reactive
hyperemia). Nonapical (rest of body): almost complete lack of AV anastamoses, sympathetic
postganglionic acetylcholine innervation active vasodilation (sweat glands).
Q: What are the neural factors that regulate cutaneous blood flow in apical skin? Whats the
pathway for passive vasodilation?
A: Sympathetic adrenergic innervation of Arterioles, AV anatsamoses (glomus bodies), Venules.
At rest, reflex stim causes vasoconstriction of cutaneous vessels. Withdrawal of sympathetic
nerve activity produces passive vasodilation.
Q: What are the neural factors that regulate cutaneous blood flow in nonapical skin? Whats the
pathway for active vasodilation?

A: Sympathetic vasoconstriction (NE), active vasodilation by sympathetic cholinergic fibers

through sweat-dependent release of bradykinin. Symp cholinergic stim causes bradykinin release
which causes active vasodilation.
Q: What are the thermal factors that regulate cutaneous blood flow? What is the control area?
What happens with increased internal temperate and decreased internal temperature?
A:Hypothalamus (anterior / preoptic area) controls thermoregulation. Inc internal temp
sympathetic withdrawal vasodilaiton (inc cutaneous flow). Maximal vasodilaiton from
complete symp block. Dec internal temp actives sympathetic activity inc vasoconstriction (dec
flow).
Q: Is there a local thermoregulatory effect in the skin?
A: Yes, moderate temp changes in skin temperature has similar responses in flow to global.
Q: How does changes in blood pressure due to baroreceptor regulation affect a normothermic
person and a person in heat stress? What about an inc in BP in warm conditions?
A: Normothermic: skin is only 5-10% of CO, any change in press = small effect on TPR and BP.
Heat stress: flow can be very high (60% of CO), any decreases in BP significant baroreceptormediated vasoconstriction of cutaneous vessels to inc BP. Competes with vasodilation (reflex
temperature regulation), limits vasoconstriction effect making BP not as well maintained. In
warm conditions inc BP withdrawals symp activity but little effect as apical is already dilated.
Q: What are the effects of exercise on cutaneous flow initially? With continued exercise? With
extreme exercise intensity and duration?
A: Initially: sympathetic vasoconstriction shunts blood from skin to active muscle. With inc
exercise and inc internal temp, temp regulation reflex stims vasodilation for cutaneous heat loss.
Changes from net vasoconstriction net vasodilation. After limit of vasodilation and high
cutaneous blood flow from exercise, extreme exercise cant increase flow / heat loss more which
leads to significant increase in internal temperature (hyperthermia / heat stroke).
Q: What are the general features of the splanchnic circulation? Address: what organs, venous
blood content, % of CO.
A: Supply to abdominal organs: GI tract, liver, pancreas, spleen. 25% of CO during rest/fast.
Venous blood has CO2, metabolites, and nutrients from GI lumen.
Q: Describe the microcirculation (intestinal villus) system. VERY IMPORTANT
A: Countercurrent flow system. Incoming arteriole courses up center, branches into capillaries.
Capillaries converge into venules back to base of villus. Arteries and venules run parallel. Solutes
(Na+) absorb into capillaries venules interstitum arterioles. Increases arteriolar
osmolarity which increases blood flow. Also happens in the renal system.
Q: What are the features of the hepatic portal system? Where does it collect blood from? What is
the normal portal vein pressure, why does that matter? What are the percentages of blow flow
into the portal system?

A: Collects from capillary beds of intestines, stomach, pancreas, spleen. 25-30% of flow from
hepatic proper artery, 70-75% of flow from portal vein. Normal pressure 10mm Hg, slightly
higher than IVC.
Q: What are the effects of portal hypertension? What would a patient present with if it is severe?
A: Portal HTN (>25 mmHg) can cause abdominal edema / ascites. Can lead to dilated portalcaval anastamoses esophageal, capit medusae (stomach), hemorrhoids (rectal). With rupture,
leads to vomiting of blood, hemorrhoid bleeding that wont clot (damaged liver).
Q: What are the metabolic local regualtory mechs for splanchnic blood flow? Discuss both
increases and decreases in general, mucosal blood flow.
A: General: inc meatbolism causes O2 dec and metabolite inc. Both cause vaodilation and
increase intestinal blood flow. Dec metabolism causes O2 inc and metabolite decreases
vasocontriction and intestinal blood flow reduction. Mucosal blood flow increases due to
increased metabolism & inc O2 demand.
Q: What is the primary determinant of intestinal blood flow?
A: Active transport rate of solutes across the mucosal epithelium (independent of intestinal
content).
Q: Does autoregulation play a role in intestinal blood flow?
A: Moderate autoregulation with inc metabolites vasodilation, dec metabolites
vasoconstriction.
Q: What is the mechanical effect on splanchnic blood flow? What is the effect on muscularis
layer and the overall effect? What other organ is this like? What disease has this?
A: Inc intestinal motility modestly increases smooth muscle metabolism in the muscularis.
Overall total intestinal blood flow decreases during intestinal contractions due to vessel
compression (like the heart). This can lead to ischemia like in Crohns diseases = painful.
Q: What are the 2 hormones that have effects on gastrointestinal blood flow?
A: Cholecystokinin and neurotensin increase blood flow by causing vasodilation.
Q: What is the major neural influence on intestinal blood flow? Do all vessels receive this
innervation? What is the neurotransmitter?
A: Postganglionic sympathetic vasoconstrction is the major influence. All splanchnic vessels
except for capillaries receive sympathetic innervation. Norepinephrine is the sympathetic NT.
Q: What is the effects of the 2 main types of sympathetic receptors on intestinal blood flow?
A: Alpha-adrenergic receptors cause vascular smooth muscle vasoconstriction. Beta-adrenergic
receptors cause vasodilation.
Q: What happens to intestinal blood flow during stress / exercise (lion kind of stress)?

A: Sympathetic vasoconstriction shunts blood to skeletal muscles, heart and brain.

Q: What happens to splanchnic blood flow during hemorrhage? What are the long term effects?
A: Hemorrhange / significant blood loss, shunts blood away from splanchnic to central
circulation. Can lead to ischemic bowel with intense / prolonged sympathetic vasoconstriction.
Q: What is the parasympathetic activity effect on intestinal blood flow?
A: Indirectly increases blood flow by increasing motility inc metabolism vasodilation.
Q: What is postprandial hyperemia?
A: Food ingestion increases instestinal blood flow. Complex interplay of metabolic, mechanical,
neural, and hormonal. Lumen content also is a role = fats & carbs are very effective in hyperemia.
L23 Fetal
Q: What are changes that occur following clamping of the umbilical vein?
A: Decreases pressure in RV, decreased pressure in pulmonary circuit easier lung flow,
Increased pulomonary flow increased LA pressure. Septum primum closes, atrial chambers
separated.
Q: What are the changes that lead to the ductus arteriosus closing following birth?
A: Increased systemic vascular resistance due to crying, moving, and clamping of umbilical
arteries. Lungs opening also decreases PVR. Flow reverses in ductus arteriosus. Bradykinin
production from the inflated lungs.
Q: What valve shuts following birth? How does that work?
A: Foramen ovale closes as the LA goes from being lower pressure than the RA to high pressure.
This causes septum primum to flap back over the foramen ovale and seal the septum secundum,
creates the fossa ovalis.
Q: What other pipes / vessels close following birth?
A: Ductus venosus (liver shunt) and arteriosus (pulmonary trunk shunt) close to due the increase
in arterial sided pressure, no placenta (sink), and inflation of the lungs (inc pressure, drops
resistance, & bradykinin production).
Q: In the hemoglobin curve, what does a shift to the right mean? What hemoglobin does this
correspond to? Do the same for shift left.
A: Shift right = Decreased affinity = Increased unloading. Happens with Hemoglobin A. Shift left
= Increased affinity = Decreased unloading/Increased uptake. Happens with Hemoglobin F.