Flashcards in Combined Test 1 Deck (347):
what determines coronary blood flow? what regulates it?
- determines: aortic pressure- regulates: metabolic activity/changes in arteriolar resistance
when do you see a reversal in the blood flow of the left- but not right- coronary artery?
during max systolic pressure (isovolumetric contraction- rapid ejection) aka early systole
60-65% of coronary blood perfusion to LV muscle occurs during ______
Vessels in the endocardium or epicardium are more compressible? Which vessels are more dilated? Which is more at risk for ischemia?
- endo to ALL
What compress endo/epicardium vessles?
Diastolic pressure and contraction
what is the relationship between blood flow and metabolic activity?
linear* increased metabolism, decreased resistance, increased blood flow
what are the metabolic substrates for the heart, and what is the largest consumer of O2?
fatty acids (LARGEST O2), carbs, ketones/lactate/proteins
how does the heart get more oxygen?
it is flow limited- must vasodilate
what is the equation for cardiac work, and which factor matters more?
cardiac work= MAP x systolic stroke volume (W=F*D)- pressure is more important
which factors affect myocardial oxygen supply?
- diastolic perfusion pressure - coronary vascular resistance (external vs intrinsic (metabolites)) - O2 carrying capacity
which factors create largest O2 demand?
- afterload- heart rate- contractility
what is ischemia, considering O2?
imbalance in the ratio of oxygen supply to oxygen demand; creates a relative lack in blood flow- excessive O2 demand is NEVER the primary cause (always too little supply)
what is coronary steal?
an increase in blood flow to one region can cause a decrease in flow to another- * problematic with vasodilation if there is a stenosis *
when would coronary steal present clinically?
- exercise-induced ischemia- stress testing- peripheral arterial disease
What happens to skeletal muscle circulation during exercise?
- the flow oscillates- overall, there is a significant reduction in resistance to blood flow to vasodilation
Skeletal flow can increase ___ time during exercise, which is called _____. It constitutes the ____ vascular bed in the body. Which type of muscle has more vascular supply- tonic or phasic?
20 active hyperemialargesttonic
What is the main vasodilator- working against sympathetics- in skeletal muscle?
Skeletal muscle vasculature is primarily innervated by _____ fibers
Ach causes ___ by acting on ___ coupled to ___
vasodilation muscarinic (on endothelials) NO production
Epinephrine from ____ causes ____ at low concentrations through activating _____, but _____ at high concentrations through activating ____
- adrenal medulla- vasodilation - beta-2 adrenergic receptors- vasoconstriction - alpha adrenergic receptors
The brain primarily uses _____ metabolism of _____. How metabolically active is it?
aerobic metabolism of glucosemost metabolically active tissue in the body
What is the BBB due to? What can cross?
- endothelial tight junctions- basement membrane- neuroglial processes - metabolic enzymes - lipid soluble substances- O2, CO2, ethanol, steroids, glucose
What is CPP? If CPP falls, what happens? What reduces CPP?
- cerebral perfusion pressure- CPP= MAP- intracranial venous pressure - vasodilation - reduced by decrease in MAP or increase in intracranial pressure
what is the monroe-kellie doctrine?
brain volume + cerebral vascular volume + CSF volume= constant
What happens as CSF pressure rises?
- increase CSF pressure- cerebral blood flow decreases (veins compressed) - metabolic autoregulation dilates the arteries- this only works up until a certain pressure, where the arteries become compressed
Cerebral blood flow is very sensitive to which metabolite?
An increase in pH (hyperventilation) causes what? This helps with what clinical scenario?
- vasoconstriction & decreased blood flow- cerebral edema (high intracranial pressures)
mechanism for nitric oxide
- causes vasodilation of smooth muscle - increases cGMP and PKG- increases phosphorylation of MLCK- decreases phosphorylation of myosin light chain
what is the cushing response?
with elevated intracranial pressure, you see - high blood pressure (medulla sympathetics)- low heart rate (parasympathetics)
when does the cushing response occur?
when CSP (cerebral spinal pressure) is greater than the mean arterial pressure
Pulmonary circulation is a ____ pressure, ____ volume system, ___ resistance; mean pressure gradient= ____
low pressure, high volume, low resistancemean pressure gradient 6 mm Hg
Pulmonary arteries are ___ compliant than regular arteries because____
7x more; they lack smooth muscle
Pulmonary capillaries represent ___ of the vascular resistance
T/F Pulmonary vessels autoregulate
During inspiration, negative pressure ______'s extra-alveolar vessels and _____ resistance in alveolar vessels - net effect on resistance = ?
distends; increases net effect- no change!
intravascular (hydrostatic) pressure is greatest at which part of the lung? what does this cause?
bottom waterfall effect
what happens in zone 1?
alveolar pressure exceeds arterial and veous pressures, causing capillaries to collapse- exists w/ hypotension or positive pressure mechanical ventilation
what happens in zone 2?
alveolar pressure exceeds venous pressure but does not exceed arterial pressure; capillaries are partially collapsed, is the upper 1/3rd of lung
what happens in zone 3?
arterial and venous pressures exceed alveolar pressure; flow depends on AV pressure gradient
primary function of cutaneous circulation
maintain a constant body temperature - provides transport of heat to the body surface for exchange with the environment
what is apical skin?
- high surface-volume ratio that favors heat loss- has lots of AV anastomoses called glomus bodies
what is nonapical skin?
- lacks AV anastomoses- innervated by sympathetic fibers- postganglionics release Ach; vasodilation
neural control of apical skin
sympathetic adrenergic nerves that produce vasoconstriction of cutaneous vessels (withdrawal produce passive vasodilation)
neural control of nonapical skin
- sympathetic vasoconstriction (NE) - active vasodilation via cholinergic fibers via bradykinin
temperature regulation (what kind?) is primarily controlled by major sensory sites in the ______ and less by receptors in the spinal cord
core body temperature; hypothalamus
fetal circulation pathway
fetal branch villi- umbilical vein- ductus venosus- IVC- RA- foramen ovale- LA-LV- aortasome blood goes RA- RV-pulm artery- ductus arteriosis- systemic circulation
valves close, pressure changes, pipes shut
valves close- foramen ovale
pressure changes- atria
pipes shut- ductus venosus & ductus arteriosus
difference between HbF and HbA and why?
HbF has greater affinity for O2 due to DpG shifting O2 dissociation curve left- more saturation at lower pressures
umbilical arteryumbilical veinductus venosusductus arteriosus
umbilical artery- medial umbilical ligament
umbilical vein- ligamentum teres
ductus venosus- legamentum venosus
ductus arteriosus- ligamentum arteriosum
what happens with skin circulation and exercise?
sympathetics want to vasoconstrictinternal metabolic heat stimulates cutaneous vasodilation
what does the arrangement of vessels within the intestinal villus form?
contercurrent flow system; arteries and venules run parallel to each other- solutes such as sodium dissolve from the arteries back to the venules to increase osmolarity/blood flow
What ist he portal system?
1- portal vein- blood from intestine/stomach/pancreas (only a few mmHg higher than IVC)2- liver capillaries- blood from portal vein3- hepatic vein- liver capillaries 4- IVC
metabolic control of splanchnic circulation
increase metabolismO2 decreasesmetabolites (CO2, H+, adenosine) increasevasodilation (moderate autoregulation)
hormonal control of splanchnic circulation
cholecystokinin & neurotensin increase vasodilation
neural control of splanchnic circulation
- sympathetic vasoconstriction via NE acting on alpha adrenergic receptors on vascular smooth muscle (also have beta receptors) - parasympathetics act indirectly by contacting sympathetics in intestinal wall & stimulates motility
what is postprandial hyperemia?
after eating, get increase in intestinal blood flow due to metabolic/hormonal/neural/mechanical influences
what is the equation for ejection fraction?
EF= EDV-ESV/EDV * 100 (normally 60%)
what is the ejection fraction a clinical index of?
left ventricular contractility
systolic heart failure
decreased contractility (depends on activity)- shifts contractility line down
diastolic heart failure
decreased compliance, reduced preload (can't fill normally because volume creates more pressure) - shift diastolic pressure-volume curve up
factors that determine preload
- pressure gradient from atria-ventricle - time for ventricular filling (hr)- ventricular compliance - atrial function (kick)
factors that determine contractility
- sympathetic nerve activity- drugs (digitalis) - disease (infarct)
factors that determine afterload
- aortic pressure (hypertension) - ventricular outflow tract resistance (valvular or subaortic stenosis) - ventricular size- dilated hearts= larger afterload
rate at which blood returns to the thorax (central venous pool) from the periphery
central venous pool
the volume of blood enclosed by the right atrium and great veins (IVC, SVC)
cardiac output and what it equals
rate at which blood leaves CVP and is pumped out of the heart; equals venous return
relationship between cardiac output and central venous pressure? which variable is independent? what is this called?
as you lower cardiac output (& venous return), the blood backs up in the central venous pool & you get a higher central venous pressure up CO/VR, down CVP (inverse relationship)CO is the independent variable vascular function curve
what is Pmc? what is it a relationship between? what is it normally?
- mean systemic circulatory pressure- the pressure in the venous system that occurs when the heart stops; - relationship between volume of blood and the capacity of the system (venous tone)- 7 mmHg
what happens when CVP= Pmc?
blood flow ceases- have no gradient for return
if you increase cardiac output, what happens?
decrease CVP, increase venous return (via pressure gradient)
what happens at negative CVP?
large veins collapse
which curve does transfusion shift?
vascular function curve - higher CO for lower pressure
which curve does sympathetic stimulation shift?
cardiac function curve- increases venous tone which increases venous return - higher CO for lower pressure (shifts up and left)
increase venous return by increasing peripheral venous pressure (PVP)
- increased sympathetic venoconstriction - increased skeletal leg pump - increased blood volume - cardiac contraction
increase venous return by decreasing central venous pressure (CVP)
- respiratory pump activity (decreased intrathoracic pressure)- cardiac suction (heart going from circular to oblong)
how do valves change venous return?
maintain pressure gradient between peripheral and central venous pools
where do you measure CVP (central venous pressure) graphically?
intersection of vascular function curve and cardiac function curve
which curve does heart failure shift?
- cardiac function curve- shifts down progressively - hypervolemia also shifts vascular function curve out
2 main things that shift venous function curve
blood volumevenous tone
what happens with hemmorage?
- shifts the venous function curve down;\- sympathetics boost it back up AND boost the cardiac function curve to give you same CO at reduced CVP
what is Poiseuille's law?
flow= (change in pressure)/(resistance)ORflow=(change in pressure * pi * r^4)/ (8*L*viscosity)
what is the main way in which flow is regulated?
by changing vessel radius (r^4)
what is viscosity; what is the equation; how does it relate to velocity, hematocrit, and radius
- lack of slipperiness- viscosity= sheer stress/sheer force (p/v)- inverse relationship w/ velocity- direct relationship with hematocrit - direct relationship with radius due to axial streaming
what is the definition of a non-newtonian fluid?
a fluid whose viscosity changes based on sheer stress (pressure) and force (velocity)
as a vessel diameter gets smaller, hematocrit _________ because of ________
decreases; plasma skimming
laminar vs turbulent blood flow
laminar- parallel concentric layersturbulent- disorderly patterns (murmurs, endothelial damage, thrombi); leads to Krotokoff sounds
what is the reynold's # and its equation?
- propensity for turbulent blood flow- R#= (density*diameter*velocity)/(viscosity)
what is Bernouilli's principle and its equation?
in CONSTANT FLOW system (aka there are no escape routes), total energy remains constant total energy = potential energy + (1/2)*(density *velocity^2)aka if blood is going faster, will have decreased lateral pressure on the walls
what is the laplace relationship and its equation?
- the force ripping the balloon apart - wall tension= (pressure * radius)/wall thickness
what happens with an aneurysm?
decreased velocityincreased pressureincreased radiusdecreased wall thicknessALL increase wall tension
example of low wall tension
capillaries in feet- have small radius, can resist a lot of force
what allows arterioles and precapillary sphincters to control vessel diameter and blood flow?
- a high wall thickness/radius ratio; this provides low wall tension (laplace)- also have low volume-high pressure- low compliance- high resistance
cross sectional area and the velocity of blood flow
total cross sectional area is inversely related to the velocity of blood flow
what holds 60% of blood volume
veins (larger cross sectional area than arteries)
series vs parallel resistance
-series- add them up (think vessles- aorta to large arteries to capillaries to arterioles, etc.)- parallel- less than an individual- (think organs- open more up, have less resistance)); inverse- 1/r1 + 1/r2 etc
what is pulse pressure and where does pulse pressure become greater?
- systolic-diastolic pressure- further you go away from the heart- greatest in ankle- large in arteries
what is mean arterial pressure? what is MAP determined by? what happens to it throughout the circulatory system?
- avg pressure in the aorta and proximal arterial system during one cardiac cycle - diastolic pressure + 1/3 PP- declines- driving force- greatest in aorta?
3 layers ('tunica') of arterial wall
- intima: connective tissue, endothelials, IEL- media: smooth muscle & EEL- adventitia- connective tissue w/ vasa vasorum, innervation
relationship between compliance and pressure
higher compliance (e.g. elastin), lower pressure
wall thickness/diameter ratio tells you what
greater ratio, better control of the system- greatest in arterioles, provides lots of resistance
where are continuous capillaries found?
muscle, connective tisues
where are fenestrated capillaries found?
where are discontinuous/sinusoidal capillaries found?
liver, bone marrow, spleen
what is the 'windkessel'/hydraulic filtering?
when the aortic valve closes, the recoil of the aorta wall recoiling (was pushed out by systolic pressure) sends a second wave of pressure throughout the system, maintaining diastolic pressure
relationship between compliance and pulse pressure
low compliance- high pulse pressure- high afterload- high O2 consumption
what is pressure pulse?
the wave of energy that passes through the aorta at 5 m/sec and increases to 10-15 m/sec in arteries- velocity increases as compliance decreases
what are some specific determinants of mean arterial pressure?
- cardiac output (hr * sv)- peripheral resistance(& baroreceptor, exercise, disease)- blood volume- arterial compliance
primary determinants of systolic & diastolic pressure?
systolic- cardiac outputdiastolic- peripheral resistance
if you decrease compliance, what happens to pulse pressure?
decrease compliance, increase pulse pressure
increase resistance, what happens to pulse pressure?
increase diastolic pressure (and some systolic)
what regulates peripheral arterial resistance?
changes in the arteriolar radius (viscosity would, but doesn't change)
two types of ways to change arteriolar radius?
local- myogenic, endotheial, metabolites global (extrinsic)- baroreceptor, hormonal, sympathetics (aka not specific)
which is the main player of the autonomic nervous system in regulating mean arterial pressure?
sympathetics- acts on heart, veins, arterioles (increases HR, contractility, veno/vasoconstiction)- increasing CO increases BP
changes that occur during exercise
- cardiac output rises (increase in contractility and hence stroke volume) BUT when HR reaches max, SV decreases - systolic pressure rises (increase in SV) - peripheral resistance decreases (skeletal capillaries open up) - enhanced O2 extraction- increases venous return (muscle and respiratory pump, venoconstriction)- pulse pressure widens - MAP increases- more time in systole
structures of microcirculation
precapillary resistors (arterioles, metarterioles, sphincters), exchange vessels, and venules
characteristics of capillary blood flow
- slow- intermittent, not uniform/1 direction- follows pressure gradients
what is a Rouleaux formation?
- stacks of RBCs- blood cells squeezing through capillaries at an angle, touching allows for good gas exchange
pressure gradients in capillaries
hydrostatic- 32 to 15osmotic- 25
what is the main force that holds things in? what is the most clinically relevant protein and what does it attract?
- plasma osmotic (oncotic) pressure- albumin- attracts sodium (and water back into blood); produced by liver
what determines capillary hydrostatic pressure?
pre and post capillary resistance to arterial and venous flow
what happens when you decrease the pre/post capillary resistance ratio?
- decrease pre resistance- more water flowing in OR- increase post resistance- less water able to flow out- OVERALL increase capillary hydrostatic pressure
when hydrostatic pressure is greater than osmotic pressure, you get
examples of vasodilators
prostacyclins, EDRF, NO, adenosine, H+, CO2, K+
examples of vasoconstrictors
important structural features of lymphatic system
- unidirectional flow of plasma & protein- valved, thin walls- non-fenestrated, no smooth muscles- return to subclavian veins
factors governing lymph flow
- amount of filtration- skeletal muscle activity- valves
specific causes of edema
- reduction in plasma protein (albumin- liver failure), renal disease- increase cap. hydrostatic pressure (congestive heart failure)- increased permeability of membrane (burns)- lymphatic obstruction (surgery)
what is edema?
excess fluid accumulation in interstitial space
which has a greater influence on hydrostatic pressure- arterial or venous pressure?
- venous; excessive arterial pressure is normally dissipated by resistance
what is resting sympathetic tone and what is it due to
- vascular constriction under resting conditions (basal tone) plus a small level sympathetic nerve activity due to being awake- due to tonically released norepinephrine
active vs passive mechanisms
- can be sympathetic or parasympathetic - active- change in resistance away from basal arterial tone- passive- change in resistance towards basal tone
two types of inputs
sympathetic adrenergic- increases resistancesympathetic cholinergic- decreases resistance
which type of sympathetic fibers cause active vasodilation?
sympathetic cholinergics (release Ach as opposed to Ne)
what are alpha-1 receptors?
- adrenergic receptors - on vascular smooth muscles- cause vasoconstriction - not on coronary/cerebral vessels (never want to constrict flow to the brain or the heart)
what are beta-2 receptors?
- adrenergic receptors- on heart, are secondary receptors that stimulate heart rate and contractility- on smooth muscles, cause vasodilation
located on carotid sinus (MOST BLOOD FLOW IN BODY) & aortic arch (structures with LESS vascular smooth muscle)
- are mechanoreceptors (respond to stretch)- fire more frequently by an increase in arterial pressure (vice-verse for decrease) - join 9&10 to medulla - decrease in stretch/firing= increases sympathetics and inhibits parasympathetics
ways sympathetics/PS change via baroreceptor
1) peripheral vasoconstriction (sympathetics)2) increase in heart rate (s and ps)3) increase in contractility (s)
baroreceptors respond to changes/absolute pressure and are more responsive to phasic/constant pressure
changes & phasic
what are chemoreceptors activated by?
low arterial PO2****, high arterial PCO2 (shifts curve up), and high H+
at a low CO2 concentration, receptors are ___ sensitive to a drop in O2
what do chemoreceptors stimulate?
vasoconstriction (sympathetics) bradycardia (parasympathetics) BUT this is overruled by respiratory system which promotes tachycardia (stretch receptors in the lungs inhibit vagal nerve activity)
what is the hormonal control of the circulator system? over what time frame and circumstances does it take place?
- renin-angiotensin-aldosterone- dehydration or heart failure over weeks
- increase in fluid volume- low arterial pressure (baroreceptors)- renin is released from JGA kidney cells in afferent arterioles - renin converts angiotensinogen to angitensin 1- ACE enzymes in lungs & kidneys convert 1 to 2- result in vasoconstriction of renal vessels- stimulates aldosterone release which pulls Na back into blood from kidneys- acts on hypothalamus to stimulate thirst and ADH
local mechanisms responsible for vascular resistance
autoregulation (myogeneic, metabolic)endothelialmechanical
what is autoregulation? what are the two primary mechanisms?
- when an abrupt increase in flow caused by an increase in arterial pressure is counteracted by an increase in resistance to maintain constant flow - myogenic (smooth muscle contracts in response to stretch)- metabolic (production of adenosine, H+, Co2= VASODILATORS)
auto-regulation among different organs
strong- heart, brain, kidney, skeletal muscleweak- splanchniclittle- skin, lungs
what is it called when you see a decreases in diameter in response to an increase in pressure with or without the endothelium
what is it called when you see an increase in diameter in response to an increase in pressure gradient, but only with endothelium; what it is due to
endothelial-mediated mechanism (exercise); due to increase in sheer stress of blood, result of increase in EDRF
what is active hyperemia?
increased blood flow caused by increased tissue activity (skeletal and cardiac muscle)
what is reactive hyperemia?
overshoot of blood flow in response to a metabolic debt created by a temporary occlusion
how does mechanical activity regulate blood flow?
increase in tissue pressure (think during a bicep curl) compresses small vessels and alters blood flow
where does mechanical activity regulate blood flow
muscle contraction, alveolar pressure, tumors, aortic stenosis
what is shock a primary reaction to?
cardiovascular system is unable to supply enough blood to the body; LOW BLOOD PRESSURE
Refractory characteristics of slow vs fast APs
slow- time dependent- Ca2+ - longerfast- voltage dependent- Na+
R on T phenomenon- PVCs
a premature beat (R wave) occurs during the relative refractory period of the previous beat (T wave) aka premature ventricular contraction- PVCs= polymorphic ventricular tachycardia
what is special about the refractory period of the AV node
have post-repolarization refractoriness- protects the ventricles during atrial fibrilation - depends on Ca2+ channels
In atrial fibrillation, what is determining the rate and rhythm of the ventricular activation?
AV node refractory characteristics
How do you slow ventricular rate in patient with atrial fibrilation?
Calcium channel blocker or Beta blocker
as HR goes up, which part of the cardiac cycle shortens most
action potential duration equals what part of the cardiac cycle and what part of the EKG
what causes prolonged Q-T syndrome (T wave is super late)
acquired- bradycardia, hypokalemia, quindinecongenital- defects in sodium and potassium channels e.g. Torsades (doesn't repolarize normally is AP is too long, can be initiated by R on T)
hierarchy of cardiac pacemaker activity
arranged based on inherent beating rate: SA node > latent atrial pacemakers > AV nodal/His bundle (junctional) > bundle branches > Purkinje's
diastolic depolarization- SA node
-T-type Ca current (at - voltages, Ca in) - hyperpolarization-activated inward current od sodium (funny channels) - deactivation of K+ current- inward Na/Ca exchanger
diastolic depolarization- Purkinje fibers
- hyperpolarization-activated inward current of sodium (funny channels) - deactivation of K+ current
things that change heart rate
1- slope of diastolic depolarization 2- change in maximum diastolic potential (resting potential)3- change in threshold 4- change of pacemaker
how would vagal nerve stimulation affect an EKG recording?
would have a longer R-R (less bpm)
what is sinus arrhythmia
variability in pacemaker cycle length caused by respiratory changesinspiration- increase HR- inhibits PS nerve activityexpiration- decreases HR- stimulate PS nerve activity
heart rate is slower during expiration/inspiration
molecular reasons for cardiac arrhythmia
impulse formation, conduction, or both
electrical mechanisms responsible for dysrhythmias
altered automaticity, re-entry of excitation, triggered activity
causes of tachy-dysrhythmias
NE (sympathetics)stimulants (caffeine)stretching (aneurism) sick sinus syndrome, fever, hyperthyroidism (BUSH)
causes of brady-dysrhythmias
drugs (beta blockers, calcium channel blockers, digitalis) barbiturates, anestheticsishchmia/infarctsick sinus syndromeaging
causes of re-entry excitations
ischemiainfarctioncongenital bypass tracts (WPW)
causes of DADs
"Delayed afterdepolarization" digitaliselevated catecholaminesrapid heart beatEVERYTHING TOGETHER
causes of EADs
"Early after depolarization" acidosis (ischemia) hypokalemiaquinidineslow heart rates
3 requirements for re-entry of excitation
1- geometry for conduction loop2- slow or delayed conduction3- unidirectional conduction block
1- drugs (Ca channel blockers, beta blockers)2- radio frequency ablation3- DC cardioversion4- implantable cardioverter-defibrillator
PR interval length
QRS complex length
QT interval length
cardiac E-C coupling steps (CICR)
1) AP goes down into T-tubules2) Depolarization activates L-type Ca2+ currents on sarcolemma & t-tubule membrane3) Influx of Ca2+ binds to SR and opens Ryr channels 4) Released Ca2+ binds to troponin C5) Relaxation occurs when Ca2+ is removed
structure-function EC coupling: sarcolemma
- propagates action potentials- controls Ca2+ influx via slow inward Ca2+ current
structure-function EC coupling: T-tubules
- transmits electrical activity to cell interior - located at Z-lines
structure-function EC coupling: SR, terminal cisternae
- where Ca2+ influx triggers opening of Ca2+ release channels
structure-function EC coupling: SR, longitudinal cisternae
- cite of Ca2+ re-uptake to initiate relaxation
structure-function EC coupling: troponin C
- Ca2+ receptor on actin (contractile protein)
cardiac vs skeletal muscle: size, connection, activation
size: cardiac are much smallerconnection: cardiac are electrically coupled (syncytium) vs individual muscle cells activation: cell to cell conduction vs Ach transmission at NMJs
cardiac vs skeletal muscle: contraction, contraction amplitude, summation, metabolism
contraction: CICR vs voltage-sensors on Ca2+ channelsamplitude: Ca2+ influx and SR content vs frequency of APssummation: no summation vs tetanus metabolism: aerobic (35%mit) vs anaerobic (2% mit)
what is contractility, and can you change the strength of a contraction without changing it?
contractility- the inherent ability of actin and myosin to form cross-bridges and generate contractile force; determined by intracellular Ca2+ YES
what are catecholamines
NE (neurotransmitter) and E (hormone)
mechanism of catecholamines
1) bind to Beta1 receptors on sarcolemma 2) activation adenyl cyclase to increase cAMP 3) cAMP activates PKA4) PKA phosphorylates lots of stuff
what does PKA phosphorylate in the catecholamine cascade?
1- Ca2+ channels- increases calcium influx2- phospholamban- increases SRCA rate (relaxation) 3- troponin I- reduces troponin C's affinity for calcium 1&2 increase strength of contraction2&3 decrease time course of relaxation
mechanism of calcium channel blockers
1- plugs up Ca+ influx2- decreases SR release of Ca2+- leads to less contraction (VASODILATION) 3- inhibition of slow inward Ca2+ channel inhibits conduction of AV node, blocks SVT
3 factors that change muscle contraction via a change in contractility
1) catecholamines- sympathetics2) cardiac glycosides (dig)3) Ca2+ channel blockers (vasodilator, blocks SVT)
Cycle length influences contraction amplitude by altering _______ by altering the time available for intracellular Ca2+ handling
positive staircase- as heart rate increases, the strength of the contraction ____
increases- greater Ca2+ influx at higher HR, less time for Ca2+ efflux; increased SR content and release
premature beat results in a ___ than normal contraction
smaller- less time for recovery of slow inward Ca2+ current & SR release channels & re-organization of terminal cisternae - gives you a smaller CICR release
what is a PESP
post-extrasystolic potentiation- stronger than normal contraction of the heart following a premature beat- more time for recovery of Ca2+
signs of A-fib w/ radial pulse
fast heart rate (tachycardia), irregular speed of heart rate, force for each beat is different ** because of force-frequency relationship, different amounts of Ca2+ causing different forces of contraction** skipped beat is b/c not enough pressure to open aortic valve ** thumping is a PESP
contractility of the heart is ____ with a premature beat
turn on an electric stimulator (in a lab) to increase heart rate, what does it look like?
premature beat (but think stair-case effect- slowly recovers)
four factors that determine cardiac output
1) heart rate2) myocardial contractility3) preload4) afterload
what is preload dependent on? if preload were low, what would the treatment be?
- end-diastolic volume (the amount of ventricular filling) - generates passive tension - give more volume
afterload is any force that _____
resists muscle shortening e.g. arterial pressure(the load on the muscle after contraction is initiated)
a premature beat is a _____ contraction
if compliance is low, the tissue is _____; aka _____
the slope of the resting tension curve is primarily determined by
the slope of the active tension curve is primarily determined by
what is resting diastolic tension
the amount of tension that develops passively by stretching the muscle (increasing preload)initial myocardial fiber length= EDV
what is active systolic tension
the amount of isometric tension that is developed by muscle contraction at a particular preload
stretching cardiac muscle ...
a) creates more optimal overlap between the thick and thin filaments b) increases Ca2+ sensitivity of myofilaments
_____ increases the max slope of the systolic tension curve, and _____ decreases it
sympathetics; heart failure
an increase in preload ____ the amount of muscle shortening
an increase in afterload ___ the amount of muscle shortening
A positive increase in contractility changes what? (tension, relaxation, muscle shortening, velocity of shortening)
- raises peak isometric tension - enhances the rate of relaxation (sympathetics) - increases the amount of muscle shortening- increases the velocity of shortening
afterload is synonymous with what
decreases the velocity of muscle shortening decreases the amount of muscle shortening
at a given afterload, an increase in preload
shifts the curve right; increases the velocity of shortening and the max isometric force
at a given afterload, an increase in contractility
shifts the curve up and to the right; increases the velocity of shortening and the max isometric force
EKG inferior view of the heart
leads 2, 3 and aVF
EKG lateral view of the heart
leads 1, aVL, V5, V6
EKG anterior view of the heart
leads V3, V4
EKG septal view of the heart
leads V1, V2
which electrode is most parallel to mean frontal plane vector? and which direction is it in?
II, down and left
order of ventricular depolarization
interventricular septum (down-right), apical depolarization (down-left), endocardial surface (down-left)
why is the vector of repolarization the same as depoarlization?
- repo starts where depo ends- repo goes from positive to negative, so vector is switched
what is the last part of the heart to depolarize?
epicardial surface of the left ventricle
where is the AP slower- endo or epi- and why?
endocardial surface- it has less Ito K+ channels, repolarization takes longer
normal angles for Einthoven's triangle
-30* - 105*
if the mean frontal plane vector is more negative than -30, which kind of deviation is it?
how to use hexaxial reference to approximate the MFPV
1- pick smallest recording of the 122- take line perpendicular to that3- see if that line is + or - (pointing right or left) 4- use that line to approximate vector
einthoven triangle method
1- sum blocks up and down for q+rs+t for two leads (1+3=2)2- plot value on triangle
things that skew MFPV
left ventricular hypertrophypulmonary hypertensionbundle branch block (right deviation w/ right block)
which part of conduction does hypokalemia affect most and what happens?
Purkinje fibers- AP lengthens and u wave pops outU wave- after T, repolarization of purkinjes
if all the QRS complexes are taller, what do you suspect?
hypertrophy- more cells= more current
phases of the cardiac cycle
atrial systole (last squeeze)isovolumic contraction (**all valves closed)ejection- rapid and reducedisovolumic relaxationfilling- rapid & reduced
units for pressure, aortic blood flow, ventricular volume, time
mm Hg (0-120)L/min (0-5)ml (20-38)0-0.8 seconds
A- atrial contractionc- ventricular contractionv- filling & emptying of atrial chamber
3rd heart sound
rapid filling of blood into a heart that dilated
4th heart sound
vigorous contraction of atria pumping into ventricle
- stenosis of aortic/pulmonic valveor- insufficient/incompetent mitral/tricuspid valve
-stenosis of mitral/tricuspid valveor-insufficient aortic/pulmonic valve
Aortic valve followed by pulmonic valve during inspiration (negative pressure caused by inspiration pulls right ventricle out, filling takes longer- negative pressure differential; more preload)
Pulmonic followed by aortic due to left bundle branch block (come closer together during inspiration)
right bundle branch block- becomes exaggerated with inspiration
- cardiac index and units- venous pressure
- 2.5-4.0 (3.1)litres/min/sq m- 3-8 mm Hg
right atrial pressureright ventricle pressure (systolic)right ventricle pressure (end-diastolic)
-2-5 (2)18-30 (25)-5-5 (2)
Pulmonary artery systolic, diastolic, mean
18-30 (25)6-12 (10)10-20 (15)
Pulmonary wedge pressureleft atrial pressure
left ventricle- systolicleft ventricle- diastolic
100-140 (120)85-105 (95)
which action potential has the longest duration?
cardiac ventricle (200 ms, 10x longer)
which action potential beings and ends at -90mV?
what is a space constant
how easily an axon can conduct electrical activity
small axon = ___ membrane resistance= ___ internal resistance = ___ space constant = ___ conduction
small axon = higher membrane resistance (but overcome by the ->) = higher internal resistance= small space constant= slow conduction
at the depolarized region, there is a ___ in membrane polarity, which causes ___ to flow
depolarization is caused by
opening of of h & m**** gates of sodium channels- rapid increase in Na+ channel conductance
repolarization is caused by
- delayed increase in K+ channel conductance;- inactivation of Na+ channels (closing of h gate)
K+ channels deactivate by
repolarization of membrane potential
Na+ channels deactivate by
positive voltage of cell (one of few positive feedback loops)
channel properties (M & H)
resting- M closed, H openactivated- m open, h openinactivated- m open, h closed
important difference between Na and K channels
K+ channels don't have H gate, are inactivated by membrane repolarization
how does a more positive resting membrane potential affect the gating of Na channels?
H-gates begin to close as membrane becomes more positive; results in slow conduction & muscle weakness
absolute vs. relative refractory periods; what channel do they depend on
- absolute- h-gate is closed- relative- hyperpolarization, where voltage difference is too great for another APNA CHANNELS!
how does calcium modulate sodium channel activity?
Ca binds to proteins surrounding Na channel, makes environment more positive, h-gate closes, less APs
increased plasma Ca+, Na+ channels become inactive (less available), conduction slowssigns: weak reflexes
blow off CO2, get less H+ in blood, get less binding of Ca2+ because of increased pH, increase membrane excitabilitysigns: agitation
increased plasma K+, less K+ leaks out of neuron, inside of the cell becomes more positive, h-gates close and get less APssymptoms: slow mentation, muscle weakness
large differences in the diameter of unmyelinated axons do/don't change conduction velocity
schwann cells increase the ______ by increasing _____
space constant; membrane resistance
where is the only place you see action potentials
nodes of ranvier
In MS, the space constant is
steps of synaptic transmission
- depolarization- calcium enters- synaptic vesicles fuse via SNARE- transmitter released into synaptic cleft- NTs bind or diffuse (NO)- NTs cleared away
two types of post-synaptic events
ionotropic- quick- opening of ion channelsmetabotropic- slow- GPCRs
BoTX mechanisms, symptoms
- cleaves SNAREs (synaptobrevin, SNAP-25, and syntaxin); prevents fusion of vesicles - affects peripheral cholinergic fibers - flaccid paralysis & autonomic symptoms
TeTX mechanisms, symptoms
- cleaves SNAREs (synaptobrevin); prevents fusion of vesicles - taken up by inhibitory neurons in spinal cord - spastic paralysis & death
types of cholinergic fibers
- all preganglionics - postganglionics of parasympathetic NS- basal forebrain- brainstem- NMJs
two types of Ach receptors
nicotinic- fast- ionotropicmuscarinic- slow- metabotropic
opening of ion channels (PSC) results in
PSP- postsynaptic potential (NOT AP)
types of excitatory NTs
Ach, glutamate- inward Na, outward K= EPSC
what is an EPSP
cation movement which depolarizes the cell to around ~0mv, **** increasing the probability that an action potential will be fired
inhibitory NTs; act on which channels
glycine, GABA; changes permeability to Cl, moves more towards -65mV and LOCKS- will always prevent AP
what does the ANS control
MOTOR SYSTEM- cardiac muscle, smooth muscle, glands- has motor efferents and visceral afferents
function of ANS
homeostasis, respond to external stimuli
major autonomic neurotransmitters
** Ach and norepinephrine (NE)**(epinephrine is central NT, but in ANS is mainly hormone)
differences between neuron-neuron (and neuron-SKM) and neuron-viscera (ANS)
- well defined vs en passant- little vs. great distance- ionotropic vs metabotropic - direct effect vs. direct&neuromodulatory effect
effects of nerve gas (sarin)
inhibits Ache, prevent Ach degredation; have too much Ach in cholinergic synapse, overstimulate muscarinic receptors causing convulsions & paralysis
treatment of WMD gases
- diazepam: seizures- atropine: blocks Ach receptors- 2PAM (pralidoxime)- recover Ache function
NT for adrenergic neurotransmission; how its terminated; where degrading enzymes exist
NE synthesized in vesicles from DOPA; MAO and COMT; degrading enzymes in cytosol, mitochondria, circulation
location of pre-ganglionic cell bodies of sympathethic NS
C8lateral horn of thoracics upper lumbar
what do preganglionic sympathetic neurons secrete
Ach- acts on nicotinic receptors- ionotropic, fast acting
location of post-ganglionic cell bodies of sympathethic NS
- para-vertebral (sympathetic trunk)- pre-vertebral ganglia (abdomen)
sympathetic pre-ganglionic fibers are shorter/longer than parasympathetic preganglionic fibers
preganglionic neurons are mostly ipsilateral/contralateral except for ___, which are bilateral
ipsilateral; pelvic viscera/intestines
why is the adrenal medulla an exception
preganglionic neruons PASS THROUGH splanchnic; have NO post ganglionic neuron- is nicotinic - causes bolus release of NE/E into blood
why are sweat glands an exception
they're sympathetic, but activated by Ach NOT NE
sympathetic post ganglionic fibers normally secrete
autonomic centers in brain
pons (breathing)medulla (blood vessels)hypothalamus (master)
similarities between skeletal, smooth and cardiac muscle
all use Ca2+all require actin & myosinchemical energy comes from ATP
smallest to largest muscle components
myofilament -> sarcomere -> myofibril -> myofiber
what happens to the I, A, and H bands during contraction
A band (myosin) stays the sameI band (actin) shrinksH band (between actins) shrinks
steps in EC coupling
- action potential goes down t-tubule- depolarization activates DHPR- DHPR activates ryanodine receptors - ca2+ is released from SR- ca2+ initiates muscle contraction- SERCA pumps Ca2+ back into SR lumen
ways to regulate muscle contraction
fire successive APs (summate)turn more/fewer fibers onbuild bigger fiberschange resting length of fibers
sarcomeres in parallel add _____, but in series add _____
describe length-tension diagram
lots of stress-too short- stericsno stress- too long- no overlap
muscle contracts and shortens- (includes concentric and eccentric contractions)- tension remains constant despite a change in muscle weights (bicep curls)load < tension
muscle contracts but does not shorten; muscle actively held at a fixed length, like when you flex to show your biceps, grip an objectload = tension
what counts for 50-70% of all ATP consumed? where is the rest used up?
- actomyosin ATPase (crossbridging)- SERCA CA2+ ATPase- Na/K ATPase
sources of ATP for muscle metabolism
- creatine phosphate- 1st used and depleated- oxidative phosphorlation - glycolysis (anerobic exercise)
types of muscle fibers
type 1- slow- oxidative phosphorylation- postural muscles- lots of blood vessels/mitochondriatype 2- fast- glycolysis- fast & forceful
difference in E-C coupling between skeletal muscle and cardiac muscle
DHPR physical coupling vs Ca2+ induced Ca2+ release
weight training increases
the number of myofibrils
the number of mitochondria
relationship between alpha and beta adrenergic receptors and smooth muscle activation
- alpha decreases cAMP and beta increases it- cAMP stimulates PKA to phosphorylate MLCK, resulting in RELAXATION
relationship between nitric oxide and smooth muscle contraction
vagal stimulation increases Ach in blood, which binds to endothelial cells, causing them to release NO; NO increases cGMP which stimulates the MLCP, resulting in de-phosphorylation of the light chain and relaxation of blood vessels
sequence of electical activity
two reasons for deviation of membrane potential from Nernst equation
1) small sodium influx2) decrease in potassium permeability (inward rectification)
two causes of inward rectification
1) chemical- decrease in extracellular K+2) electrical- depolarization of the membrane
channels during fast action potential
0- fast Na channels let Na in1- transient Ito channels let K+ out2- slow calcium channels let calcium in, transient channels close, trapping K+ in3- delayed potassium channels open, letting K+ out4- K+ equilibrates (IK1's are open)
how hypokalemia affects resting membrane potential
get no net change in voltage
how hyperkalemia affects membrane potential
membrane potential becomes more positive
channels during slow AP
4- funny channels let more Na in than K+ out2- voltage Ca2+ channels open, and Ca2+ goes in3- K+ channels open, K+ leaves, get repolarization
slow vs fast AP in heart
slow- pace maker (e.g. SA cells)fast- contractile cells
what does TTX do?
block fast Na+ channels, turns contractile cells to slow conduction
3 types of junctions found at intercalated disks
fascia adherinsmacular adherinsgap junctions (connexons)
what are gap junctions sensitive to
Ca2+ and H+
properties of pacemaker cells
function: pace makesmall diameterfew gap junctionsfew myofibrils
properties of atrial and ventricular muscle cells
function: contractionmedium diameterabundant gap junctionsabundant myofibrils
properties of His/bundle branches/Purkinjes
function: rapid conductionlarge diameterabundant gap junctionsfew myofibrils
2 factors that determine cardiac conduction
1) space constant ((Rm/Ri)^1/2)2) rate of rise and amplitude of action potential
membrane resistance is ___ related to K+ permeability
internal resistance is ____ related to number of gap junction connections and ______ related to cell diameter
conduction is strictly related to which part of the action potential?
upstroke- sodium channels
conditions that can change RMP
hyperkalemiapremature excitationischemia - build of of K+ in tissue
conduction time from atrial muscle-AV node-his-purkinje- 200 ms
conduction time from endocardial to epicardial surface- 100 ms
AV nodal conduction abnormalities- type 1
abnormal prolongation in P-R interval (1:1 conduction)
AV nodal conduction abnormalities- type 2
some atrial impulses fail to activate ventricles; not all P waves followed by QRS (e.g. 2:1 conudction)
AV nodal conduction abnormalities- type 3
complete AV block; no consistent P-R interval
sympathetic innervation to the heart
- NE- acts on beta adrenergic receptors- increases speed of all things in the heart- increases cAMP and inward calcium
parasympathetic innervation to the heart
- Ach (vagal)- acts on muscarinic receptors - acts on everything up to AV node- increases K+ permeability
- narrow QRS- normal sequence, just rapid- CO not affected- filling time decreased
- QRS is abnormally prolonged- impulse originates in ventricle and skips His-Purkinje; goes in circular pattern- conduction is slow - CO compromised
- absence of P-waves (like static where they should be), R-R are irregular - non leathal
lots of random electrical activity; is probably the end
how to spot AV conduction abnormalities on EKG
look for how QRS follows p-wave