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842 Cards in this Set
- Front
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path electrical activity takes through the heart |
starts at the SA node near the SVC |
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atria and ventricles are electrically isolated from each other by the |
annulus fibrosus |
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gap junctions
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pores that join cytoplasm or neighboring cells |
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electromechanical coupling
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electrical activity is the trigger for mechanical activity |
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Cardiac muscle action potential phases
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0 - upstroke |
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AP specifics in the nodes
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slow upstroke |
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AP specifics in the atria, his bundle, purkinje system, ventricles
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stable resting potential
more rapid upstroke early repolarization plateau phase is prominent |
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more prominent plateau phases in atria, ventricles, etc are for...
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ca induced ca release to happen |
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longer AP in purkinje and his bundle...
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protect that tissue from the activity initiated in the ventricle propagating backwards |
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fastest conduction velocity in cardiac tissue
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purkinje system
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order of conduction speed, fastest to slowest, in cardiac tissue
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purkinje system
atrial pathways and bundle of his ventricular muscle SA node and AV node |
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faster conducting tissues are
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better aligned, well coupled
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distribution of ions
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More Na outside |
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ionic basis of resting membrane potential
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Ik1 current |
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resting heartcells behave like _____________ membranes
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K-selective
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experimentally, the RMP in resting heart cells is
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-85mV |
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cardiac action potentials
fast response |
atrial |
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cardiac action potentials
slow response |
SA and AV nodes
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Fast response action potential
Phase 0 Upstroke |
At rest Ik1 is open and Na channel is closed
a depolarizing current triggers activation gate of Na channels they activate and as cell beginsto depolarize the Ik1 channel closes almost immediately (Magnesium blocks it up) Currents: I(Na) - Sodium in |
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Fast response action potential
phase 1 early repolarization |
Transient outwork K current |
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fast response action potential
phase 2 plateau |
I(to) current begins to inactivate and close
activation of delayed rectifier K current L type Ca channels activate allowing calcium in for CICR for muscle contraction balance of K out and Ca in keeps membrane potential around 0mV currents: I(k) - K out I(Ca) - Ca in (eventually L type Ca channels will inactivate themselves) |
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Fast response action potential
phase 3 final repolarization |
L type Ca channels inactivate themselves |
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Fast response action potential
Phase 4 rest |
After Ik closes it's just Ik1 and the 3Na(out)/2K(in) ATPase |
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I(KATP/ACh)
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ligand gated current
ATP sensitive in cardiac myocytes opens when ATP drops during ischemia, AP duration would shorten less contraction, save some energy |
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Voltage gated K channels
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4 separate subunits form a channel
voltage sensor is the S4 segment Pore region is the S5-S6 linker N terminal is where voltage-dependent inactivation happens |
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voltage gated Na and Ca channels
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similar structure to K channels
BUT each consists of a single subunit containing four repeats Na and Ca channels are linked together, as opposed to K which are individual |
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Ik1 - inward rectifier current
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resting membrane potential |
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Ik - delayed rectifier current
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outward current during phase 2 and 3 |
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ways ion currents are modulated
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change in available current (carrier concentration or temp)
number of functional channels (changes in gene expression) probability of activation |
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Slow response action potential differences
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resting potential is less negative because Ik1 is absent
upstroke is due to inward Ca current from L type Ca channels slow diastolic depolarization during phase 4, instead of remaining locked at rest |
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rate of sinus node cell firing depends upon
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the balance between inward and outward currents
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ionic basis of automaticity
currents that contribute to diastolic depolarization |
I(f) - inward depolarizing current, induced by hyperpolarization |
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factors that influence pacemaker rate
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slope of diastolic depolarization |
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how it affects pacemaker rate
slope of diastolic depolarization |
a smaller slope of depolarization means it takes longer to reach threshold potential
it will take longer to fire |
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how it affects pacemaker rate
threshold potential |
increasing threshold potential will make it take longer to reach
it will take longer to fire |
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how it affects pacemaker rate
minimum diastolic potential |
if you have an even more negative minimum diastolic potential, you'll be further away from threshold potential
itwill take longer to fire |
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pacemaker rate
parasympathetic stimulation |
activation of I(KACh channels) - increases K conductance
lowers min diastolic potential decreases slope of phase 4 |
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pacemaker rate
sympathetic stimulation |
activation of I(f) channels -
increases slope of phase 4 no change in min diastolic potential |
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refractory period
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absolute refractory period - during upstroke and depolarization where you can't get another AP to fire at all
relative refractory period - after repolarization has started, an AP could fire but it won't be as effective |
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positive charge comes at an electrode
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positive signal
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positive signal moves away from an electrode
(negative signal moves towards it) |
negative signal
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positive or negative signal passes by an electrode
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isoelectric
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how many electrodes and how many leads?
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10 electrodes
12 leads |
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all leads are unipolar except
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I
II III |
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aVR
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right arm
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aVF
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left leg |
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aVL
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left arm
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I
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right arm to left arm
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II
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right arm to left leg
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III
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left arm to left leg |
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V1 |
Right sternal 4th intercostal |
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V2 |
left sternal 4th intercostal |
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V3 and V4 |
mid clavicular |
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V5 |
anterior axillary
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V6
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mid axillary
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path of electricity through heart and waveform
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starts at SA node
as it travels through RA, the RA contracts and you get a p wave gets to the AV node iso-electrically Down the bundle of his to the bundle branches and around is the QRS (ventricular contraction) Resetting starts from teh outside (repolarization) at the left lateral base resets outside in and makes the t wave |
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qrs through the heart
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starts in the intraventricular septum, on the edge of the left ventricle
moves away from aVL through the septum going towards aVF swings around to the rest of the myocardium inside bundle branches to get to rv and lv apex still going towards aVF and now it's also going towards aVL moves up the left bundle branch moving away from aVF and moving rapidly positive towards aVL |
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time
1 small box |
0.04 sec
40 msec |
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time 1 big box
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.2 sec
200 msec |
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voltage 1 small box
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0.1 mV
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volrtage 1 big box
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0.5 mV
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normal PR interval
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120 to 200 msec
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normal QRS interval
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60 to 100 msec
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normal QT interval
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less than 440 msec (men) or 460 msec (women)
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heart rate method 1
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count number of small boxes between qrs complexes
divide 1500 by the number f boxes most useful for fast heartbeats over 100 bpm |
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heart rate method 2
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count off method
each big box you go down in the sequence 300 - 150 - 100 - 75 - 60 - 50 |
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heart rate method 3
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number of QRS in the 3 sec marker and multiply by 20 |
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p wave
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depolarization of the top chambers
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R wave
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depolarization of the ventricles
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T wave
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repolarization of the ventricles |
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U wave
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shrug
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five steps to ecg read
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rate
rhythm axis intervals morphology |
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axis
normal |
lead I up
aVF up |
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left axis deviation
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I up
aVF down |
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right axis deviation
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I down
aVF up |
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extreme axis
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I down
aVF down |
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normal axis is between what degrees
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-30 (left) and +90 (right)
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left axis deviation is between what degrees
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-30 to -90
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right axis deviation is between what degrees
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+90 to +150
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extreme axis is between
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+150 and -90
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left axis deviation causes
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inferior wall myocardial infarction
left anterior fascicular block left ventricular hypertrophy |
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right axis deviation causes
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right ventricular hypertrophy |
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intervals (again)
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HR less than 100 bpm |
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normal p wave in lead II |
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normal p wave in lead V1 |
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p wave
RA enlargement in lead II |
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p wave
RA enlargement in lead V1 |
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p wave
LA enlargement in lead II |
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p wave
LA enlargement in lead V1 |
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RV hypertrophy in V1 |
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RV hypertrophy in V6 |
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RV hypertrophy characteristics on ecg |
R > S in V1
right axis deviation (lead I down, lead aVF up) |
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LV hypertrophy in V1 |
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LV hypertrophy in V6 |
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LV hypertrophy characteristics in ecg |
Deep S wave in V1
R in V5 or V6 is greater than 35 mm
R in aVL is greater than 11 mm
R in lead I is greater than 15 mm |
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RBBB |
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LBBB |
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the normal dynamic |
all regions start at the same baseline
ekg baseline is set during electrical diastole when everything is quiet.
no significant gradients exist between regions |
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ekg changes with ischemia |
ST elevation |
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ekg changes with ischemia |
ST elevation
decreased R wave
Q wave begins |
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ekg changes with ischemia |
T wave inversion
Q wave gets deeper |
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ekg changes with ischemia |
ST normalizes
T wave inverted |
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ekg changes with ischemia |
ST and T normalize
Q wave persists |
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ischemia and potassium |
dysfunction I(k) and I(ATP) lead to potassium leak
the cells dont have ATP/energy
region gets necrotic and swells |
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ischemia in diastole |
ischemic cells leak potassium during phase 4 causing the baseline to be more positive |
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ischemia in systole |
ischemic cells are less positive because
shorter action potential slower upstroke lower amplitude |
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ST segment elevation in MI |
injury on the outside region of the muscle, leaking potassium
gradient between the epicardium and endocardium
K going away from the electrode creates a vector away from it and that becomes the new normal baseline
ST segment is actually normal, it looks elevated compared to the new normal baseline |
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NON ST segment elevation in MI |
injured on the inside region of the muscle
leaked potassium creates a vector TOWARD the recording electrode, which forms a new higher baseline
ST region looks depressed during depolarization |
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MI Q wave |
in aVL
goes down because aVL cant see a signal coming towards it until really late
jumps up late when the healthy section at the base is seen |
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Q waves are normal due to |
left to right activation
normal in I, aVF, V5, and V6 |
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Pathologic Q waves |
> 40 ms
2 mm deep
more than 25% of the QRS amplitude
seen in V1, V2, V3 |
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anteroseptal leads |
v1 v2 |
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anteroapical leads |
v3 v4 |
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anterolateral leads |
I aVL V5 V6 |
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inferior leads |
II III aVF |
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current influx at phase 4 of a cardiac pacemaker cell |
I(f) influx |
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AP in a cardiac pacemaker cell |
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I(f) current |
activated by hyperpolarization
channels open when membrane voltage is more negative than -50mV
Mainly conducts Na ions
inward Na flow driven by conc gradient and the negative charge inside the cell |
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in the pacemaker cells of the SA node... |
slow inward Ca current carried by mostly L type Ca channels
progressive decline of outward K current
additional inward Na current via Na/Ca exchanger act by SR Ca (calcium clock) |
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what are A B and C |
A is normal nodal (slow) AP
B is reduced I(f) which means it takes longer to get to threshold potential so it fires later
C is more negative maximum diastolic potential that makes it take even longer to get to Threshold Potential |
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natural pacemaker in the normal heart |
SA node beats at 60-100 bpm
faster than other tissues with automaticity |
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SA node bpm |
60-100 |
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AV node/Bundle of His bpm |
50-60 |
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Purkinje System bpm |
30-40 |
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when an impulse arrives at a cell that has not yet gotten close to threshold |
current from the depolarized cell will bring the adjacent cell's membrane potential to threshold level so that it will fire
this is why the fastest autonomic cell will be the dominant pacemaker |
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latent (ectopic) pacemakers take over if |
SA node slows or fails to fire
if conduction abnormalities block the normal depolarization wave from reaching them |
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enhanced automaticity of latent pacemakers
ectopic beats |
impulse premature, relative to normal rhythm
high catecholamine conc can enhance automaticity of latent pacemakers
if the resulting rate of depolarization exceeds that of the sinus node, an ectopic rhythm can develop |
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ectopic beat commonly induced by |
hypoxia
ischemia
electrolyte disturbances
certain drug toxicities (dig) |
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Abnormal automaticity |
cardiac tissue injury can lead to pathologic changes in impulse formation
myocardial cells outside the specialized conduction system can acquire automaticity and spontaneously depolarize
since they arent designed to be pacemakers, they dont carry I(f), but their membranes become leaky
can't maintain conc gradients of ions and the resulting potential becomes less negative
if it becomes less negative than -60mV, gradual phase 4 depolarization is observed, even in non pacemaker cells
probably the result of a slowly inactivating Ca current and a decrease in outward K current that normally repolarizes |
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triggered activity |
action potentials can trigger abnormal depolarizations that result in extra heart beats or rapid arrhythmias
this can occur when the first AP leads to oscillation of the membrane voltage - Afterdepolarizations |
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2 types of after depolarizations |
early occur during repolarization phase
delayed occur shortly after repolarization has been completed
either way, abnormal APs are triggered if the afterdepolarization reaches threshold voltage |
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Early after depolarization |
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Delayed after depolarization |
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repetitive afterdepolarizations (like in an EAD) may produce... |
rapid sequence of APs and a tachyarrhythmia |
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DAD may trigger |
a propagated AP |
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Early after depolarizations |
changes of membrane potential int he positive direction that interrupt normal repolarization
can occur during plateau of AP (phase 2) or during rapid repolarization (phase 3)
more likely to develop in conditions that prolong AP duration (longer QT interval conditions)
appear to be the initiating mechanism of torsades |
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Delayed after depolarizations |
most common occur in states of high intracellular calcium like dig intoxication
can lead to tachyarrhythmias
some idiopathic ventricular tachycardias and atrial and ventricular tachycardias associated with dig toxicity |
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conduction block |
a propagation impulse is blocked when it reaches a region of the heart that is electrically unexcitable
can be transient or permanent
block can be unidirectional or bidirectional
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functional block |
occurs because a propagating impulse encounters cardiac cells that are still refractory from a previous depolarization
a pulse that arrives later might be conducted |
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fixed block |
caused by a barrier imposed by fibrosis or scarring that replaces myocytes |
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AV block |
conduction block within AV node or His purkinje system
prevents normal propagation of cardiac impulse from the sinuse node to more distal sites
removes the normal suppression that ikeeps latent pacemakers in the his-purkinje system in check
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av block usualy results in the emergence of |
escape beats/rhythms, as more distal sites assume pacemaker function |
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Re entry |
an electric impulse circulates repeatedly around a re entry path, recurrently depolarizing a region of cardiac tissue |
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2 critical conditions for re entry |
unidirectional block
slowed conduction through the re entry path |
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re entry
NORMALLY |
the AP propagates in a way that prevents re entry
refractory periods keep any circular paths from being accessible in the wrong direction |
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unidirectional block and re entry |
blocked region prevents normal propagation
normally, at certain junctions cells would be in a refractory period, but since the block was there, the cells are able to accept the AP in the wrong direction
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unidirectional block and re entry tends to occur in regions |
where the rafractory periosd of adjacent cells are heterogeneous
can also occur when cells are dysfunctional or fibrosis has altered the myocardial structure |
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unidirectional block and re entry
at normal retrograde conduction velocity |
eventuallly when the signal goes around the re entry loop, it will still hit a point that is still refractory and stop |
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unidirectional block and re entry
slowed retrograde conduction velocity |
by the time it gets to the spot past the initial blockage, refractory period is over
this can continue indefinitely and each pass through the loop excites cells of the distal conduction tissue which propagates to the rest of the myocardium at an abnormally high rate
tachyarrhythmia |
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mechanisms of arrhythmia development bradyarrhythmias altered impulse formation
decreased automaticity |
decreased phase 4 depolarization e.g. parasympathetic stimulation
sinus bradycardia |
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mechanisms of arrhythmia development bradyarrhythmias
altered impulse conduction
conduction blocks |
ischemic, anatomic, or drug induced impaired conduction
1st, 2nd, 3rd degree AV blocks |
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mechanisms of arrhythmia development tachyarrhythmias
altered impulse formation
enhanced automaticity
sinus node |
increased phase 4 depolarization
e.g. sympathetic stimulation
sinus tachycardia |
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mechanisms of arrhythmia development
altered impulse formation
enhanced automaticity
AV node |
increaed phase 4 depolarization
e.g. sympathetic stimulation
AV junctional tachycardia |
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mechanisms of arrhythmia development
altered impulse formation
enhanced automaticity
ectopic focus |
acquires phase 4 depolarization
ectopic atrial tachycardia and some forms of VT |
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mechanisms of arrhythmia development altered impulse formation
triggered activity
EAD |
prolonged AP duration
torsades de pointes |
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mechanisms of arrhythmia development
triggered activity
DAD |
intracellular calcium overload
e.g. dig toxicity
APBs, VPBs, digitialis induced arrhythmias, idiopathic VT |
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mechanisms of arrhythmia development altered impulse conduction
re entry
anatomical |
unidirectional block and slowed conduction
atrial flutter AV nodal re entrant tachycardia VT related to ventricular scar tissue |
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mechanisms of arrhythmia development
re entry
functional |
unidirectional block and slowed conduction
a fib polymorphic VT v fib |
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bradyarrhythmias pharmacologic therapy anticholinergic drugs |
vagal stimulation: reduces rate of sinus node depolarization (slows HR) and decreases conduction through the AV node
so anticholinergics competitively bind to the Mu receptors that ACh binds to, and reduces vagal effect
results in increased HR and enhanced AV nodal conduction |
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bradyarrhythmias pharmacologic therapy
beta receptor agonists |
mimics the effect of endogenous catecholamines
increase HR speed up AV node conduction |
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bradyarrhythmias pacemakers |
initiate depolarization at a desired rate assume control of rhythm |
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tachyarrhythmias pharmacologic therapy desired drug effects to eliminate rhythms caused by increased automaticity |
reduce the slope of phase 4 spontaneous depolarization of the automatic cells
make the diastolic potential more negative (hyperpolarize)
make threshold potential less negative |
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tachyarrhythmias pharmacologic therapy
desired antiarrhythmic effects to interrupt re entrant circuits |
decrease conduction in the re entry circuit to the point htat conduction fayils, thus stopping re entry impulse
increase the refractory period within the re entrant circuit so that a propagating impulse finds tissue within the loop unexcitable and the impulse stops
suppress premature beats that can initiate re entry |
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tachyarrhythmias pharmacologic therapy
desired drug effects to eliminate triggered activity |
shorten AP duration to prevent EADs
correct conditions of calcium overload to prevent DADs |
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arrhythmia drugs: vaughn-williams classification
class I |
predominantly Na channel blockers |
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arrhythmia drugs: vaughn-williams classification
class II |
beta adrenergic receptor blockers |
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arrhythmia drugs: vaughn-williams classification
class III |
predominantly K channel blockers |
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arrhythmia drugs: vaughn-williams classification
class IV |
non dihydropyridine Ca channel blockers |
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arrhythmia drugs: vaughn-williams classification
class V |
misc drugs (adenosine, dig) |
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Class I drugs effect on working myocytes
order of strength of effect |
IC > IA > IB |
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Class I drugs effect on working myocytes
class IA |
slows conduction decreases I(Na) smaller slope of
prolongs Action Potential Duration decreases I(k) prolongs QTc interval
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Class I drugs effect on working myocytes
example-s of class IA drugs |
procainamide quinidine disopyramide |
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Class I drugs effect on working myocytes
effects of IB drugs |
mild conduction slowing decreases I(Na) decreases slope of upstroke
shortens action potential duration decreases I(Na) and I(L) shortens QTc interval |
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Class I drugs effect on working myocytes
examples of IB drugs |
Lidocaine
mexilitine |
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Class I drugs effect on working myocytes
IC effects |
slows conduction a LOT decreases I(Na) really decreases slope of upstroke
minimal effect on Action Potential Duration QT lengthens, but only because QRS lengthens
action potential duration doesn't really change |
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Use dependency? Class IC > IA drugs |
binding to open/inactivated Na channels
plus
slow association/dissociation kinetics
means that more channels are blocked at faster heart rates
that's why these drugs are effective at terminating arrhythmias |
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Class IA clinical uses |
atrial fib
atrial flutter
supraventricular tachy
ventricular tachy |
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class IA quinidine |
anticholinergic (moderate)
side effects: cinchoism (blurred vision, tinnitus, headache, psychosis) cramping and nausea enhances dig toxicity |
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class IA procainamide |
anticholinergic (weak) short half life
side effects: lupus like syndrome |
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class IA disopyramide |
anticholinergic (strong)
side effects: negative inotropic effect |
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Class IB clinical uses |
ventricular tachy
dig induced ventricular arrhythmias |
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class IB
lidocaine |
IV only; V tachys and premature ventricular contractions
side effects good efficacy in ischemic myocardium |
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class IB
mexiletine |
orally active lidocaine analog
side fx good efficacy in ischemic myocardium |
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class IC clinical uses |
a fib a fluttter supraventricular tachy (SVT) |
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class IC flecainide |
supreventricular tachy
side fx can induce life threatening ventricular tachy |
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class IC propafenone |
supraventricular tachy
ventricular tachy
side fx beta blocking and calcium channel blocking activity can worsen heart failure |
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class IA: Procainamide indications |
conversion of supraventricular tachy
pre excited a fib
a fib/a flutter
ventricular tachy |
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class IA: procainamide mechanism |
blocks I(Na) depresses phase 0 - slows conduction
moderate K channel blocking activity prolongs Action Potential duration |
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Class IA: procainamide metabolism |
liver acetylation into NAPA
other 50-60 percent renally excreted
NAPA metabolite is 100 percent renally cleared has Class III activity as a K cahnnel blocker (markedly prolongs repolarization)
need to watch NAPA levels which are different from procainamide levels |
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Class IB: Lidocaine indications |
ischemic ventricular tachy
dig induced arrhythmias (delayed after depolarizations) |
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class IB: Lidocaine mechanism |
blocks open/inactivated state of Na channel
rapid on/off kinetics
more active in tachy arrhythmias and in depolarized tissues (ischemic)
no effect on atrial tissue because of their short action potential duration |
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class IB: Lidocaine clearance |
hepatic more toxicity with hepatic congestion (congestive heart failure)
monitor serum levels to minimize toxic effects |
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class IB: lidocaine side fx |
mainly CNS: confusion, paresthesias, dizzy, seizures |
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class IC: Propafenone indications |
SVT AFib Aflutter |
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class IC: propafenone mechanisms |
binds open state of Na channels
slow on.off kinetics
use dependency - more activity with faster heart rates good for svt arrhythmia conversion bad for scar-related, reentrant vt
can make vt incessant
has beta blocking activity like propanolol |
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class IC: propafenone metabolism |
hepatic -> hydroxypropafenone
parent propafenone has more beta blocking effect
7% are poor metabolizers that have more parent propafenone and an increased beta blocker effect |
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class IC: propafenone contraindication |
coronary disease or LV dysfunction/.structural heart disease
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class IC: propafenone side fx |
cardiac - may precipitate ventricular arrhythmias and congestive heart failure
cns - dizziness, taste disturbance
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class IC: propafenone other |
can organize afib to slower flutter allowing for 1:1 av nodal conduction |
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class II: beta blockers
indications |
SVT
AFib/AFlutter rate control
VT
Long QT patients |
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class II: beta blockers
mechanisms |
beta 1 receptor blockade reduces cAMP production
reduces PKA activity
reduces cytosolic Ca in myocardial tissue
decreases the slope of phase 4 in upstroke in nodal tissue
prolongs conduction time and refractoriness of nodal tissue |
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class II: beta blockers side fx |
bradycardia
bronchospasm
fatigue
depression
erectile dysfunction
weight gain
hyperglycemia
insomnia |
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class III drugsdo what...? |
block K currents I(Kr) I(Ks) I(K1)
pure I(Kr) blocker - dofetilide
beta blocking activity - sotalol: 1:1 d,l-isomers (d has no beta blocking activity)
enhances delayed inward Na current - ibutilide
IB, II, IV activity - amiodarone
like amiodarone but lacks iodine moiety - dronedarone |
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class III: amiodarone indications |
svt
af/avl
vt
vf |
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class III: amiodarone
mechanism |
blocks I(K) I(Na) I(Ca)
also has Class II effect |
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class III: amiodarone metabolism |
liver half life ~ 100 days |
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class III: amiodarone side fx |
thyroid, pulmonary, hpeatic, ocular, neurologic, renal
proarrhythmia Torsades - very rare
numerus drug drug interactions - raises warfarin levels |
|
|
Class IV: Ca channel blockers nondihydropyridine |
verapamil dilitazem
slowed rise of action potential prolonged repolarization at AV node
increase threshold potential of SA node decrease heart rate
decrease conduction velocity of AV node and increase effective refractory period of AV node decrease re entry and decrease av node conduction |
|
|
class effect on EKG IA |
PR 0 QRS increase QT increase |
|
|
class effect on ekg IB |
PR 0 QRS 0 QT 0 or decrease |
|
|
class effect on EKG IC |
PR increase QRS incraese QT 0 or increase |
|
|
class effect on EKG II |
PR 0 or increase QRS 0 QT 0 |
|
|
class effect on EKG III |
PR 0 or increase QRS 0 or increase QT incrase |
|
|
class effect on ekg IV |
PR increase QRS 0 QT 0 |
|
|
class V Dig indications |
svt
rate contrial for a fib |
|
|
class v dig mechanisms |
blocks Na/K ATPase which leads to inhibition of Na/Ca exchange, increasing intracellular Ca
vagomimmetic effect |
|
|
class v dig clearance |
renal excretion
half life of 36 to 48 hrs with normal renal function 3 to 5 days in anuric pts |
|
|
class v dig side effects and toxicity |
GI sypmtoms: loss of appetite, nausea, vomit, diarrhea
visual: yellow green halos and problems with colors
neuro: confusion, drowsy, dizzy, sleep disturbed, depression
cardiac: increased delayed after depolarizations. APC, VPC, paroxysmal atrial tachy with av block is pathognomonic for dig toxicity, vt or vf, heart block |
|
|
class v adenosine indication |
svt termination and diagnosis
|
|
|
class v adenosine mechanism |
adenosine 1 receptor of av node
stimulates G(i) g proteins to decrease cAMP
increase K efflux and hyperpolarization
decrease Ca channel open probability
decrease I(f)
|
|
|
class v adenosine metabolism |
adenosine deaminase in RBCs half life ~ 10 sec dipyridamole blocks adenosine deaminase |
|
|
class v adenosine side fx |
flushing heart block bronchoconstriction headache
|
|
|
class v adenosine other |
shortens action potential duration
potentiates Afib induction |
|
|
class v adenosine contraindications |
afib and wolf parkinson white syndrome: may incrase accessory pathway conduction
asthma - bronchospasms
cardiac transplants - exaggerated responses |
|
|
class v adenosine antagonists |
methylxanthines-caffeine, theophylline |
|
|
common arrhythmias in SA node
bradyarrhythmia |
sinus bradycardia
sick sinus syndrom |
|
|
common arrhythmias in SA node
tachyarrhythmias |
sinus tachycardia |
|
|
common arrhythmias in atria
bradyarrhythmias |
none |
|
|
common arrhythmias in atria
tachyarrhythmia |
atrial premature beats (APBs)
atrial flutter
atrial fibrillation
paroxysomal supraventricular tachyarrhythmia
focal atrial tachycardia
multifocal atrial tachycardia |
|
|
common arrhythmias in AV node
bradyarrhythmia |
conduction blocks
junctional escape rhythm |
|
|
common arrhythmias in av node
tachyarrhythmia |
paroxysomal reentrant tachycardia (av or av nodal) |
|
|
common arrhythmias in ventricles
bradyarrthymia |
ventricular escape rhythm |
|
|
common arrhythmias in ventricles
tachyarrhythmias |
ventricular premature beats
ventricular tachy
torsades de pointes
ventricular fibrillation |
|
|
sick sinus syndrom general |
intrinsic SA node dysfunction that causes periosd of inappropriate bradycardia |
|
|
sick sinus syndrome symptoms |
dizziness
confusion
syncope |
|
|
sick sinus syndrome treatment |
IV anticholinergics (atropine)
beta adrenergics
if chronic, a pacemaker is requirede |
|
|
elderly patients with SSS are also susceptible to |
SVTs and Afib
this combination = bradycardia-tachycardia syndrome |
|
|
Escape rhythms |
cells in the av node and his purkinje system are capable of automaticity like the sa node, but usually have slower firing rates so they don't take over
if sa node becomes impaired or if there's some kind of conduction block, escape rhythm can emerge from the more distal latent pacemakers |
|
|
junctional escape rhythm |
arise from the av node or bundle of his
characterized by a normal, narrow QRS complex
occur in sequence
appear at a rate of 40-60 bpm |
|
|
EKG of junctional escape rhythm |
qrs complexes are NOT preceeded by normal p waves because the impulse originates below the atria
retrograde p waves can be observed as an impulse propagates from distal pacemakers up to the atria
these p waves typically follow the QRS and are inverted
|
|
|
inverted retrograde p waves in jucntion escape rhythm |
negative deflection in leads II, III, aVF
indicating activation of the atria from the inferior direction |
|
|
ventricular escape rhythms |
even slower
30-40 bpm
widened qrs |
|
|
why widened qrs in ventricular escape rhythms? |
complexes are wide because the ventricles are not depolarized by the normal rapid simultaneous conduction of the right and left bundle branches
instead, from a more distal point in the conduction system |
|
|
EKG of ventricular escape rhythms |
qrs morphology depends on the site of the origin of the escape rhythm
originating from the left bundle branch will cause a right bundle branch block pattern
originating form the right bundle branch will cause a left bundle branch block pattern |
|
|
why do we have junctional and ventricular escape rhythms? |
they're protective backup mechanisms that maintain a heart rate and cardiac output when the sinus node or normal av conduction fails
|
|
|
treatment of escape rhythms |
IV anticholinergics
beta adrenergics
pacemakers if chronic |
|
|
av conduction system is made up of |
av node
bundle of his
left and right bundle branches |
|
|
what leads to av block |
impaired conduction between the atria and ventricles |
|
|
1st degree av block |
prolongation of the normal delay between atrial and ventricular polarization
the impariment is usually within the av node itself and can be caused by a transient reversible influence or a structural defect |
|
|
1st degree av block ekg |
pr interval is lengthend to >5 small boxes
1:1 P:R ratio is maintained |
|
|
reversible causes of av block |
heightened vagal tone
transient av node ischemia
drugs that depress conduction through the av node like: beta blockers some ca channel antagonists digitalis other antiarrhythmics |
|
|
structural causes of av block |
MI
chronic degenerative diseases |
|
|
1st degree av block treatment |
usually benign and asymptomatic
requires no treatment |
|
|
2nd degree av block |
characterized by intermittent failure of av conduction
|
|
|
2nd degree av block ekg |
some p waves not followed by qrs complexes |
|
|
2nd degree av block
mobitz type 1
wenkebach block |
degree of av delay gradually increases with each beat until an impulse is completely blocked
almost always results form impaired conduction in the av node |
|
|
2nd degree av block
mobits type 1
wenkebach block
ekg |
a qrs does not follow a p for one beat
you see a progressive increase in PR interval until a single qrs is absent
then PR goes back to initial length and the cycle starts over |
|
|
2nd degree av block
mobitz type 1
wenkebach block
treatment |
usually benign
treatment is typically not necessary
in symptomatic cases administration of atropine or isoproterenol improves av conduction transiently
permanent pacemaker required for symptomatic block that does not resolve spontaneously |
|
|
2nd degree av block
mobitz type 2
|
sudden intermittent loss of av conduction without preceeding gradual lengthening of the PR interval
usually caused by a block beyond the AV node in the bundle of his or purkinje system |
|
|
2nd degree av block
mobitz type 2
ekg |
PR interval isn't changing but a qrs just gets dropped
may persist for 2 or more beats multiple Ps are NOT followed by QRSs known as high grade av block
qrs is often widened in a pattern like right or left bundle branch block |
|
|
2nd degree av block
mobitz type 2
treatment |
more dangerous than type I and treatment with a pacemaker is usualy warranted, even in asymptomatic patients |
|
|
3rd degree av block |
complete heart block
presenet when there is complete failure of conduction between the atria and ventricles
electrically disconnects the atria and ventricles
atria depolarize in response to SA node more distal escape rhythm drives the ventricles independently
caused by MI or chronic degeneration |
|
|
3rd degree av block
ekg |
no relationship between p waves and qrs complexes
p wave rate is not related to qrs intervals |
|
|
3rd degree av block treatments |
permanent pacemaker is almost always necessary |
|
|
tachyarrhythmias |
when HR is > 100bpm for 3 beats or more
results from: enhances automaticity re entry triggered activity |
|
|
supraventricular tachyarrhythmia (SVT) |
arises above the ventricles |
|
|
ventricular tachyarrhythmia |
arises from within the ventricles |
|
|
SVTs
sinus tachycardia |
sa node discharge rate >100bpm
normal p waves and normal qrs complexes
usually results from increased sympathetic or decreased vagal tone |
|
|
SVTs
atrial premature beats |
originate from automaticity or re entry in an atrial focus outside the SA node
often exacerbated by sympathetic tone |
|
|
SVTs
atrial premature beats (APBs)
ekg |
appears as earlier-than-expected p wave with an abnormal shape
qrs is usuallly normal. if they're wide, it's apb with aberrant conduction |
|
|
SVTs atrial premature beats (APBs) treatment |
only req treatment if they're symptomatic
caffeine, alcohole, stress can predispose to APB
beta blockers are the initial preferred treatment |
|
|
SVTs
Atrial flutter |
rapid, regular atrial activity at a rate of 180-350 bpm
many of these impulses reach AV node during refractory period and dont conduct to the ventricles |
|
|
SVTs
atrial flutter
example of 2:1 block |
300bpm at atria
150 bpm at ventricles
|
|
|
SVTs
atrial flutter
ekg |
p waves have a sawtooth appearance
faster rates (>100bpm) cause palpitations, dyspnea, weakness |
|
|
SVTs
atrial flutter
treatment |
vagal maneuvers like the carotid sinus massage decrease AV conduction and further lower ventricular rate
antiarrhythmics that reduce the rate of atrial flutter can be dangerous because they allow the av node more time to recover between impulses.
AV node may begin to conduct 1:1 atria could be 280bpm w/ 2:1 block, 140 bpm ventricles
if the atrial rate slows to 220bpm, the ventricle rate could accelerate to 220bpm |
|
|
SVTs
atrial flutter
treatment, drugs etc |
electrical cardioversion to restore sinus rhythm
rapid atrial pacing w pacemaker
beta blocker, ca channel blocker, or digitalis to slow ventricular rate
then restore sinus rhythm with antiarrhythmics that slow conduction or prolong refractory period (class IA, IC, III)
catheter ablation |
|
|
SVTs
atrial fibrillation |
chaotic rhythm with atrial rate so fast that distinct p waves are not discernible on ECG (350-600 discharges/min)
avg ventricular rate in untreated A Fib is 140-160 bpm
mechanism probably involves multiple wnadering re entrant circuits within the atria |
|
|
SVTs
atrial fibrillation
ekg |
irregularly irregular rhythm
ecg baseline shows low amplitude undulations puncutated by QRS complexes and T waves
|
|
|
SVTs
atrial fibrillation
symptoms and signs |
Afib is often associated with enlarged L or R atrium
heart failure, hypertension, coronary artery disease, pulmonary disease ^^^all promote AFib because they promote atrial enlargement |
|
|
why is a fib so bad? |
rapid ventricular rates may compromise cardiac output leading to hypotension and pulmonary congestion
absence of organized atrial contraction promotes blood stasis in atria, increasing risk of thrombus formation, especially in left atrial appendage |
|
|
SVTs
afib
treatment considers 3 things |
ventricular rate control
methods to restor esinus rhythm
assessment of the need for anticoagulation to prevent thromboembollism |
|
|
SVTs afib
drug treatment |
similar to Atrial Flutter
beta blockers and calcium channel antagonists promote block in av node and reduce ventricular rate
digitalis is less effective
class IA, IC, III antiarrhythmics are used to restore sinus rhtyhm ^^have bad side fx so they're not used in asymptomatic patients
AFib for more than 48 hours needs anticoagulation
MAZE procedure and catheter ablation are alternatives to antiarrhythmics
catheter ablation can be used to induce complete AV block and slow ventricular rate. a permanent pacemaker is needed after this |
|
|
SVTs
Paroxysmal supraventricular tachycardias (PSVTs) |
sudden onset and termination atrial rates between 140 and 250 bpm
narrow (normal) qrs complexes
mechanism is most often re entry involving AV node, atrium, or an accessory pathway
enhanced automaticity and triggered activity in the atrium or AV node are less common causes |
|
|
SVTs PSVTs
AV Nodal Re Entrant Tachycardia (AVNRT) |
most common form of PSVT in adults
there can be multiple potential pathways through the AV node and they can conduct at different velocities
the slower pathway usually has a shorter refractory period |
|
|
SVTs
PSVTs
AVNRT pathway |
Atrial premature beat travels to the junction between slow and fast pathways conducts down slow pathway since it has a shorter refractory period and already repolarized
by the time it gets to the compact portion of the AV node, the distal end of the fast pathway has repolarized and the signal can go distal to the bundle of his AND backwards up the fast pathway toward the atrium
at the top of the fast pathway it comes back down thte slow pathway = loop |
|
|
SVTs PSVTs
EKG |
ecg shows a regular tachycardia with normal width QRS
retrograde p waves usually get hidden in QRS but they can sometimes be seen at the terminal portion of QRS complex
they'l be inverted in leads II, III, aVF since the atrial activation is going "up" |
|
|
SVTs PSVTs AVNRT symptoms and signs |
usually tolerable with just palpitations
rapid tachycardias can cause lightheadedness or shortness of breath
elder patients can get syncope, angina, pulmonary edema |
|
|
SVTs PSVTs AVNRT
treatment |
acute terminate re entry by imparing conduction in AV node valsalva maneuver or carotid sinus massage may block AV conduction and terminate the tachycardia
pharmacologic IV adenosine impairs AV nodal conduction and aborts re entrant rhythm other options= beta blockers and calcium channel antagonists
catheter ablation or class IA, IC antiarrhythmics might be used for chronic problems with AVNRT |
|
|
SVTs
Atrioventricular Re entrant Tachycardias (AVRTs) |
similar to AVNRTs except one limb of the loop is made up of an accessory tract instead of 2 separate slow and fast pathways through the AV node |
|
|
accessory tract |
bypass tract an abnormal band of myocytes that spans the AV groove and connects atrial to ventricular tissues separately from the normal conduction system |
|
|
Ventricular pre-excitation syndrome Wolff Parkinson White syndrome |
atrial impulses can pass in an anterograde direction to the ventricles through both the av node and the accessory pathway
conduction through the accessory pathway is usually faster than that via the AV node
ventricles are stimulated earlier than by normal conduction over the AV node |
|
|
Ventricular pre excitation syndrome WPW syndrome
ekg |
during sinus rhythm: PR interval is short because ventricular stimulation starts earlier than normal
QRS is widened because it represents the fusion of 2 events (conduction through both pathways) |
|
|
ventricular pre excitation syndrome WPW syndrome treatment |
pharmacologic management
have to be more careful than with AVNRT patients
beta blockers, calcium channel antagonists, and digitalis all can block condcution through the av node but they do not slow conduction over the accessory pathways |
|
|
Common ventricular arrhythmias |
VPBs VT VFib |
|
|
Ventricular premature beats (VPBs) |
similar to APBs, VPBs are common and often asyptomatic and benign
a VPB arises when an ectopic ventricular focus fires an action potential |
|
|
VPBs
ekg |
appears as a widened QRS complex because the impulse travles from its ectopic site through the ventricles via slow cell to cell connections rather than the faster his-purkinje system |
|
|
VPBs
treatment |
in healthy patients, treatment is reassurance and symptomatic use of beta blockers
if patients have advanced structural heart disease with features that place them at risk for life-threatening arrhythmias, placement of an inflatable cardioverter defibrillator (ICD) is recommended |
|
|
Ventricular Tachycardia |
series of 3 or more VPBs |
|
|
sustained VT |
persists more than 30 sec
produces sever symptoms like syncope or requires termination by cardioversion or administration of a drug |
|
|
unsustained VT |
self terminating episodes |
|
|
VT EKG |
qrs complexes are wide (>0.12sec) 100-200 bpm
|
|
|
monomorphic VT |
QRS complexes all look the same and rate is regular |
|
|
polymorphic VT |
qrs complexes change in shape and rate varies |
|
|
symptoms of VT |
vary depending on the rate, duration, underlying condition
sustained VT can cause low cardiac output leading to syncope pulmonary edema cardiac arriest
but if it's slow (<130bpm) it might only cause palpitations |
|
|
distinguishing monomorphic vt from supraventricular tachycardia |
width of the qrs complex
monomorphic vt = wide
svt = narrow (normal) unless SVT with aberrant ventricular conduction
|
|
|
SVT with aberrant conduction occurs in: |
patients with underlying conduction abnormality like a bundle branch block
repetitive rapid ventricular stimulation durign SVT finds one of the bundle branches refractory
pt develops antidromic tachy through an accessory pathway |
|
|
managing patients with VT |
acute treatment = cardioversion iv administration of antiarrhtyhmics, procainamide/lidocaine
after sinus rhythm is restored: determine whetehr underlying heart disease exists
correct aggravating factors like: electrolyte disturbances drug toxicities
beta blockers, calcium channel blockers, catheter ablation are commonly effective to control symptomatic episodes of idiopathic VT |
|
|
torsades de pointes |
a polymorphic VT that presents as varying amplitude of QRS
can be produced by EADs (triggered activity) particularly in patients with prolonged QT intervals |
|
|
torsades symptomes |
light headed
syncope
main danger is from degeneration into VFibt |
|
|
torsades treatment |
when it's drug or electrolyte induced, correcting the underlying cause abolishes recurrences
in other cases, administration of IV magnesium represses episodes
also: shorten QT intervals via beta adrenergic stimulating agents or an artificial pacemaker
if torsades is because of a congenital prolongation of QT, beta blockers are preferred sympathetic stimulation aggravetes the arrhythmia in many such individuals |
|
|
ventricular fibrillation |
immediately life threatening
results in disordered, rapid stimulation of the ventricle with no coordinated contractions
result = no cardiac output and death if not quickly reversed
VF is often initiated by an episode of VT that degenerates into multiple smaller wavelets of re entry that wander the myuocardium |
|
|
Ventricular feibrillation
treatment |
only effective therapy is prompt electrical defibrillation
after the heart has been converted to a safe rhythm, correct underlying issues: electrolyte imbalances, hypoxemia, acidosis
IV antiarrhythmics can be administered to prevent immediate recurrences |
|
|
inherited arrhythmogenic disease
familial arrhythmia |
monogenic diseases with mendelian inheritance
conditions include: channelopathies cardiomyopathies ion channels proteins muscle proteins |
|
|
IAD channelopathies |
long qt syndrome
short qt syndrome
brugada syndrome
catecholaminergic vt
idiopathic vt/vf |
|
|
IAD cardiomyopathies |
dilated
hypertrophic
arrhythmogenic RV/LV
restrictive
non compaction |
|
|
background of IADs |
relative rare -> 1:500 to 1:10000
young people [childhood -> midlife]
high risk of sudden cardiac arrest/arrhythmia |
|
|
3 representative examples of genetic mutations leading to arrhythmias |
long qt syndrome
brugada syndrome
hypertrophic cardiomyopathy |
|
|
where to you measure the QT interval? |
lead II or V5 |
|
|
Long QT Syndrome 1 LQTS1 |
k current
decreases
mostly exercise triggered |
|
|
Long QT Syndrome 2 LQTS2 |
k current
decreases
mostly emotional stress triggered |
|
|
Long QT Syndrome 3 LQTS3 |
Na current
increases
mostly triggered during sleep/repose |
|
|
LQTS2
HERG channel |
hERG channel makes the alpha subunit of the k channel that does the I(kr) current
conducts K out of the cell to make repolarization happen
if it's blocked or doesn't correctly undergo conformational changes, it can be deficient in the amount of K it pumps out
pumping out K less effectively can prolong the repolarization phase of a cardiac myocyte's action potential |
|
|
LQTS risk by QTc |
there is stratification among the quaqrtiles
the shortest QTs (closest to normal) are associated with better survival than the longer QTs |
|
|
LQTS mechanisms |
abnormal impulse can lead to triggered event
DAD reaches threshold and fires off in a triggered way
EAD can trigger arrhythmia |
|
|
LQTS treatment |
beta blockers
work best for LQT1 then LQT2 then LQT3 |
|
|
Brugada syndrome |
right bundle branch block and ST segment elevation in leads V1, V2, V3
a marker for sudden death in patients without demonstrable structural heart disease |
|
|
brugada syndrome ekg |
ST segment elevation and what looks like RBBB but it's "coved" or elongated/wide
especially in v2
the ekg is really dynamic though. it can change through out the day, |
|
|
brugada symptoms |
cluster by age most abundant in 31-40 year olds and 41-50 year olds
|
|
|
SCN5A |
the Na channel messed up in brugada
has three states: resting, open, inactivated
resting state is closed compoletely
depolarization causes it to open up and Na can come into the cell
eventually it inactivates. It stays open but it's plugged on the cytosolic end. This plug is responsible for the refractory period
once inactivated the channel needs repolarization to reactivate |
|
|
phenotypic heterogeneity in brugada |
different presentations from the same channel
coving of the QRS can be highlly variable from pt to pt |
|
what is this notch |
the I(to) current activates at phase 1 and pumps K out, but the balancing action of Na in is defective, so membrane potential gets negative more quickly than usual, without the gradual plateau |
|
|
brugada causes a gradient between what? |
between endocardium and epicardium
the epicardium is the one that has the deeper notch. the endocardium looks relatively less affected. |
|
|
|
|
|
brugada re entry |
endocardium and epicardium fire cardiac action potentials but the epicardium ap collapses
an early afterdepolarization fires off and stimulates another part of the Epi. that part fires backwards to the first part of epi and then back up to the endocardium |
|
|
brugada treatment |
quinidine
catheter ablation
whatever you do, the most important thing is to prevent the v fib in the first place |
|
|
mutations in hypertrophic cardiomyopathy
|
just about anythign int he cardiac sarcomere
troposin I, troponin T, tropomyosin, actin |
|
|
pathologic elements to HOCM |
LVOT obstruction
impaired disatology
Mitral regurg/papillary muscle displacement
ischemia
dysautonomia |
|
|
treatable at all levels |
for sudden death: ICD
for progressive heart failure: drugs, myectomy
for end stage: transplant
for AFib and stroke: drugs like warfarin |
|
|
relation between LV wall thickness and sudden death |
incidence of sudden death rises with LV wall thickness
above 30 milimeters there's a super high risk |
|
|
myectomy |
scrape out the thick portion of the septum
increases survival |
|
|
prior cardiac arrest or sustained vt |
ICD recommended |
|
|
family history - SD in first degree relative or LV wall thickness >30 mm
or recent unexplained syncope |
ICD reasonable |
|
|
nonsustained VT
abnormal BP response |
ICD can be useful if there's
LVOT obstruction LGE+ LV apical aneurysm genetics |
|
|
alcohol and caffeine causing arrhythmias |
caffeine can release norepi
heavy drinking can make you lose elctrolytes(?) |
|
|
what does it tell you if an arrhythmia is or isn't exercise induce? |
if it's not exercise induced then it's probably not related to a coronoary problem |
|
|
what do diving into a swimming pool or defecation do to help alleviate arrhythmia? |
induce vagal tone
if this works, it implies that the arrhythmia is related to the AV node
you wouldn't expect a ventricular arrhythmia to respond to vagal toneh |
|
|
hyp[ertension and diabetes with arrhythmia? |
they're risk factors for heart diseasec |
|
|
chest trauma with arrhythmia? |
could be scarring |
|
|
where do atrial premature beats come from |
pulmonary veins |
|
|
if atrial premature beat hits the right atrium |
it can find its way into a pathway involving the whole thing:
IVC SVC tricuspid annulus coronary sinus
leads to atrial flutter |
|
p wave morphologies |
first one is normal
second one implies the LA is enlarged
third one implies the RA is enlarged
a fib would be most likely if LA was enlarged |
|
|
PR interval changes |
if av node was diseased the PR interval would get longer
a shorter PR interval could occur if the AV node is getting bypassed |
|
|
narrow complex tachycardia |
implies it's going through the normal pathwayw |
|
|
wide complex tachycardia |
would imply that a different pathway is being used and that they tachy is ventricular |
|
|
if you give a patient adenosine and it breaks the tachycardia |
it means the tachycardia involves the AV node |
|
|
what clinical and ecg features suggest a supraventricular etiology? |
vagal maneuvers stop it
narrow qrs, preceded by p wave, looks "normal" |
|
|
what is differential from a wide qrs tachy |
svt with rbbb hyperkalemia wpw syndrome - delta waves |
|
|
sudden on, sudden off in ekg suggests which mechanism for tachy |
reentry |
|
|
why are beta blockers successful in controlling this arrhythmia |
beta blockers impair AV nodal conduction and there are exta-atrial beats |
|
|
arrhythmia conference chart
sinus tachycardia |
not dependent on av node
has organized atrial activity
regular rhythm but could warm up and cool down
gradual onset/offset |
|
|
arrhythmia conference chart
atrial tachycardia ectopic atrial focus |
not dependent on av node
has organized atrial activity
regular
gradual onset/offset |
|
|
arrhythmia conference chart
atrial fibrillation |
not dependent on AV node (originates in pulmonary veins in LA)
no organized atrial activity
not regular
rapid onset/offset |
|
|
arrhythmia conference chart
atrial flutter |
not dependent on av node - caval tricuspid isthmus
has organized atrial activity (250-240ms) sawtooth waves
v1 has what look like p waves
could be regular or irregular
rapid onset/offset |
|
|
arrhythmia conference chart
AVNRT |
dependent on av node
organized atrial activity
regular
rapid onset/offset |
|
|
arrhythmia conference chart AVRT |
dependent on av node activity and accessory pathway
organized atrial activity
regular
rapid onset/offset with delta wave |
|
|
blood flow |
actual volume of blood flowing through a vessel, organ, or the entire circulation in a given period
measured in ml/min
equivalent to cardiac output
relatively constant at rest
varies through individual organs according to immediate needs |
|
|
which tissue has the most blood flow at rest? |
kidneys |
|
|
radial artery: inactive hand
high pulsatility waveforms are a feature of circulatory systems with high resistance to blood flow (High peripheral resistance) |
|
|
radial artery: active hand
lower resistance to blood flow? |
|
|
bernoulli's principle |
as the speed of a moving fluid increases, the pressure within the fluid decreases
to keep the total energy the same, if velocity goes up, pressure has to go down |
|
|
pressure and flow relationship |
as stenosis severity increases, blood velocity increases to maintain flow
at 75% stenosis, flow begins to decrease and the pressure generated downstream decreases creating a pressure gradient |
|
|
vascular physiology principles (3) |
diastolic flow is important to maintain adequate tissue perfusion
an increase in blood velocity occurs at a stenosis
at 75% stenosis flow and pressure decrease |
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aneurysm definition |
to widen or dilate
focal dilatation with at least 50% increase over normal arterial diameter
>3cm in abdominal aorta
1.8cm for iliac arteries
abdominal aortic aneurysm present in 6-9% of men over 65 years old in US |
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ascending aortic aneurysm |
characterized by cystic medial degeneration degeneration and fragmentation of elastic fibers, accumulation of collagenous and mucoid material within the medial layer
occurs most commonly with aging and hypertension
other causes: marfan syndrome loeys-dietz syndrome ehlers danlos syndrome bicuspid aortic valve syphilis vasculitis |
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abdominal aorta epidemiology
traditional risk factors |
increasing age
smoking
male sex
genetic
screening for AAA in old men improves morbidity and mortality |
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CT scan of abdominal aortic aneurysm |
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at what diameter does rupture risk start for AAA |
4-5 cm |
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aortic wall tension |
pascal's principle requires that pressure is the same everywhere inside the balloon at equilibrium
but examination revelas that there are great differences in wall tension on different parts of an aortic aneurysm
variation is described by laplace's law - wall tension is proportional to the product of pressure and radius
pressure stays the same, radius goes up, so tension goes up - leading to rupture |
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AAA therapy |
medical smoking cessation hypertension therapy like beta blockers, ace inhibitors, angiotensin receptor blockers
endovascular therapy lower early risk -problems over time
open therapy up front risk - better durability over time |
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Peripheral Artery disease - how many patients have symptoms |
1 in 5 people over 65 has PAD
only 1 in 10 of these patients has classical symptoms of intermittent claudication (walking leading to pain. stopping and it gets better) |
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clinical presentations of peripheral artery disease |
50% asymptomatic 33% atypical leg pain 15% classic claudication 1-2% critical limb ischemia (gangrene or pain at rest) |
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relationship between increased age and peripheral vascular disease |
for PAD, once you reach 70 incidence exponentially goes up |
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ultrasound velocity signal in PAD |
monophasic waveform
only see broad upstroke through all of systole, no diastolic backflow |
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normal vessel characteristics |
laminar flow
endothelial cell mediated vasodilation
distal pressure and flow maintained |
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PAD vessel characteristics |
high resistance
collateral vessel
turbulent flow
pressure drop across stenosis
impaired endothelial function
inability to increase flow with exercise |
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dx of PAD includes... |
atherosclerosis
vasculitis
fibromuscular dysplasia
trauma
thrombotic disorders
vascular tumor |
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claudication |
cramping, tightness, aching, fatigue
exercise induced
does not occur with standing
standing up relieves it
goes away in less than 5 minutes |
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pseudoclaudication |
cramping, tightness, aching, fatigue, tingling, burning, numbness
variably induced by exercise
does occur with standing
sitting relieves it
takes 30 minutes to go away |
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PAD comprehensive vascular exam includes |
pulse examination: carotid radial brachial femoral pooliteal dorsalis pedis posterior tibial
physical exam: cardiac exam palpation of abdomen for potential aneurysm auscultation for bruits examination of lower extremities |
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measureing ankle brachial index ABI |
pressure in ankle should be higher or the same, but not lower
take highest pressure in L and R ankles and divide by the highest arm pressure (whichever arm is highest)
anything above 0.91 is normal, below that is pathologic |
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exercise and leg pressure |
should NOT have a drop in pressure when you exercise |
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ABI vs mortality |
as ABI decreases, risk of mortality increases
but once you get to >1.4 you have incompressible arteries - different problem |
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PAD therapy exercise |
exercise does better than intervention |
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PAD medical therapy |
smoking cessation
lipid modification - statins
HTN control
antiplatelets
diabetes control
foot care
risk factors
symptomatic relief - cliostazol and pentoxifylline |
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stroke - vision complaints? |
opthalmic artery
one of the first early warning signs |
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hollenhorst plaque |
you can see a cholesterol embolus in the retina from the internal carotid artery |
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carotid artery disease
medical therapy |
antiplatelet therapy
anticoagulation
risk factor modification - smoking cessation, statins, HTN, diabetes control |
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arteriovenous malformations |
defects in the vascular system
direct connections between arteries and veins
it is believed that they often result from mistakes during embryonic or fetal development
can happen anywhere but are most common in brain or spinal cord
greatest potential danger is hemorrhage
treated via surgery or focused irradiation |
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leading cause of death in the US |
atherosclerosis |
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risk factors for coronary artery disease |
herditary: mutations and strong family history
homocyssteine Lp(a) Clotting and inflammatory factors
lipids: increased LDL, decreased HDL, increased Tg
smoking
diabetes
HTN
obesity
sedentary lifestyle |
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hsCRP |
baseline levels of the inflammation marker hsCRP in apparently healthy men can predict the riskk of first MI or ischemic stroke
aspirin reduced inflammation which is a component of athersclerosis |
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atheroma formation stage 1 |
retention of Apo B lipoprotein particles enter the tunica intima from the lumen and are retained |
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atheroma formation stage 2 |
retained lipoprotein particles are likely modified (oxidized and aggregated)
intima gets larger, more lipid shows up |
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atheroma formation stage 3 |
monocytes are attracted to the artery, which they enter and turn into macrophages
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atheroma formation stage 4 |
macrophages ingest retained lipoproteins "foam cells" die and make fatty streak |
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atheroma formation stage 5 |
other immune cells enter and area ctivated
inflammatory cytokines, chemokines, proteases, free radicals cause further tissue damage
cap between fatty and thrombogenic mess protects it from rupturing |
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hallmarks of defective inflammation resolution in atherosclerosis |
persisten influx
defective egress
retained lipoproteins
necrosis
thinning of fibrous cap |
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thinning of fibrous cap |
two processes: synthesis involves Platelet derived growth factor and TGF-beta inducing smooth muscle cells + collagen and elastin to make the cap
degradation: t lymphocytes release interferon gamma which inhibits the synthesis and make cd40L which causes foam cells to release MMPs that degrade the matrix and thin the cap |
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rupture |
when the cap gets too thin, the atheroma can rupture
when blood and fat mix a thrombus forms |
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endothelial dysfunction |
chemical irritants and hemodynamic stress can cause dysfunction of the endothelium
lipoprotein entry, inflammatory cytokines
chemokines and leukocyte adhesion molecules
leykocyte recruitment
you can improve endothelial function by lowering blood pressure and dialyzing lipid
unregulated uptake of modified LDL
foam cell formation |
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2 major adverse consequences of endothelial dysfunction |
increased recruitment of inflammatory cells
loss of NO mediated vasodilation |
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what does arginine do for vasorelaxation? |
NO synthase makes NO out of arginine
NO can diffuse to smooth muscle cells and induce relaxation by increasing cGMP |
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atherosclerotic endothelium allowing vasoconstriction |
there's a breakdown between the conversion of arginine to NO
instead of NO you make OONO (peroxy nintrates) preventing vasodilatory response |
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consequence of proximal obstruction |
a region becomes inadequately perfused |
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angina pectoris |
discomfort of thoracic cavity that comes on with exercise and goes away after |
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early atheroma can go two ways |
stable plaque small lipid pool thick fibrous cap preserved luman
vulnerable plaque large lipid pool thin fibrous cap many inflammatory cells |
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vulnerable plaque |
ruptures and forms thrombus
it can heal with a narrowed lumen and fibrous intima or you can get an acute MI |
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angina of two sorts |
demand angina comes on with exercise
resting angina - unstable a plaque rupturing |
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therapeutic opportunities for plaque rupture |
lower apoB lipoproteins
dampen inflammation and restore homeostasis
enhance efferocytosis and restore fibrous cap |
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atherosclerosis pathophysiology stage 1 |
endothelial dysfunction
HDL prevents cell adhasion, LDL promotes cell adhesion
too much LDL and platelets and monocytes adhere to the vessel wall |
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atherosclerosis pathophysiology stage 2 |
smooth muscle emigration from media to intima
macrophage activation
macrophages come from lumen sm muscle comes from tunica media |
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atherosclerosis pathophysiology stage 3 |
macrophages and smooth muscle cells engulf lipid
they get engorged and make a fatty streak |
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atherosclerosis pathophysiology stage 4 |
smooth muscle proliferation
collagen and other ecm deposition
extracellular lipid
vessel wall becomes very full because of all the ECM junk
fibrofatty atheroma is visible |
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atherosclerosis 4 stages condensed |
endothelial injury leads to dysfunction adhesion of monocytes and platelets and lipid influx
migration of macrophages and smooth muscle cells into the intima
phagocytosis by macrophages and smooth muscle cells of lipids = fatty streaks
proliferation of SMCs and deposition of ECM: fibrofatty atheroma |
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TGF-beta |
major role in fibrosis stage 4
an inhibitor of TGF-beta might inhibit atherosclerotic process |
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what's this? |
macrophages ldoaded with lipids |
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dangerous of fibroatheromas |
increased demand can't get met because of blockage
in the plaque you can have a hemorrhage
intra plaque hemorhage can make plaque bigger and cause more occlusion
ultimately you can get a thrombus formation in the lumen |
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atherosclerosis complications |
thrombosis
embolism
aneurysm and rupture
dissection |
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aneurysm definition |
dilatatio of segment of vessel |
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true aneurysm |
bulging because the whole lumen is bulging |
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false aneurysm |
something in the vessel wall is causing the bulge, like an extravasation of blood |
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difference between fusiform and saccular aneurysms |
you can't clip a fusiform aneurysm because the whole thing is bulging
you CAN and probably SHOULD clip a saccular aneurysm |
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aneurysm etiologies |
atherosclerotic
infectious (syphilis)
inflammatory
autoimmune
degenerative
traumatic |
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aortic dissection |
hole in the wall of the vessel
a small local dissection causes pain but a big one is fatal
entry point is an atheromatous lesion
a weak point that lets the blood flow get into the vessel |
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contributing factors to aortic dissection |
aging
atherosclerosis
hypertension in 60-70 percent
marfan or ehlers danlos syndromes |
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type a dissection |
proximal dissection with variable distal extension
ascending part is dissected could occlude coronary arteries or carotid arteries and mess with perfusion to heart or brain
these patients need to go to the OR |
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type b dissection |
distal dissection
tend to rupture into the left thorax
only the descending part is dissected
they usually need medical management |
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aortic dissection complications |
external rupture: in 90 percent may be fatal
compression of origins of arteries coronary carotid renal mesenteric arteries |
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vasculitides
classify based on the type of blood vessel they affect |
giant cell arteritis - lg vessels
polyarteritis nodosa - med vessels
wegener granulomatosis - small vessels
buerger's disease - mixed |
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giant cell arteritis |
over 50y headaches
palpable tender nodularity of artery
visual problems, blindness
ESR markedly elevated
polymyalgia rheumatica
steroid therapy |
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polyarteritis nodosa |
young adults
acute, subacute, or chronic
rever, weight loss, abdominal pain, melena, muscular aches, peripheral neuritis
untreated, fatal, either during an acute fulminant attack or following a protracted course
corticosteroids - remission or cures in 90% of cases |
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polyarteritis nodosa |
transmural inflammation (neutrophils, eosinophils, mononuclear cells)
fibrinoid necrosis
later, fibrousd thickening
all stages of activity may coexist in different vessels or even within the same vessel |
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wegener granulomatosis |
males > females, 40 yo
syndromes similar to PAN and respiratory involvement
fever, persistent pneumonitis, chronic sinusitis
mucosal ulcerations o fthe nasopharynx
renal disease
skin rashes
muscle pain, joints, neuritis
eye, skin, and heart
untreated, aggressive course; 80% death |
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buerger's disease |
more prevalent in young adult men smokers
immunologic and thrombogenic mechanisms
only smoking cessation stops disease activity |
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Deep veint thrombosis and pulmonary embolus |
thromboembolism is seen in over 275000 americans annually
deep veinsof the calf
therapeutic emergency: heparin |
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risk factors for dvt |
dehydration
prolonged bed rest
surgery
fractures of hip or femur
massive trauma
stroke
heart attack
cancer
oral contraceptives
childbirth |
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pulmonary embolus |
often in hospitalized patients
shortness of breath, chest pain, syncope, hemoptysis
chest x ray, CT, pulmonary ventilation/perfusion scan, pulmonary angiogram |
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pulmonary embolus treatment and prognosis |
thrombolytic and anticoagulant therapy
death rate - 30% if undiagnosed, 3% with early diagnosis and treatment
with large emboli mortality >50% |
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varicose veins |
distended veins because valves cant keep the blood up |
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relationship between cholesterol and coronary heart disease risk |
increase cholesterol, increase rate of death from heart disease |
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naturally occurring lipids and their functions |
triglycerides - energy storage
cholesterol - important precursor of steroid synthesis
phospholipids - important components of cell membranes |
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lipoproteins |
allow insoluble lipids to travel in blood
apolipoproteins are found on the surface and serve as ligands for cellular receptors |
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VLDL |
in the liver |
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IDL |
catabolism of VLDL |
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LDL |
catobolism of IDL
bad cholesterol |
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HDL |
liver, intestine, other
good cholesterol |
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bile salts |
solubilize cholesterol coming from the liver |
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VLDL and LDL cholesterol transport |
VLDL loses ApoC-II and becomes IDL
IDL loses ApoE and becomes LDL
LDL has ApoB-100 left and can enter muscle/heart/adipose tissue or participate in atherogenesis |
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prevention of atherosclerotic cardiovascular disease |
primordial prevention prevent the development of risk factors for CVD
primary prevention prevent the first CVD event
secondary prevention prevent subsequent CVD events |
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benefits of LDL reduction |
lowering LDL may slow progression, stabilize, or reverse atherosclerosis
lowering LDL improves endothelial cell function
lowering LDL prevents MI and improves survival |
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Non HDL calculation |
total cholesteral minus HDL cholesterol
this has shown to be a stronger predictor of cardiovascular risk than LDL cholesterol |
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treatment of dyslipidemia |
diet and exercise!!
statins
intestinal acting cholesterol lowering agents like bile acid sequestrants and cholesterol absorption inhibitors
nicotinic acid
fibric acid derivatives
statins-HMGCoA reductase inhibitors
fish oil
new drugs for extremely high ldl
emerging classes - pcsk9
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bile acids |
breakdown product of cholesterol
40-70% reabsorbed in the small bowel
act as detergent - help - make cholesterol soluble |
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inhibition of bile acid reabsorption |
bile acid sequestrants
cholestyramine colestipol colesevelam ^^aka WelChol - also lowers blood sugar (reduces Hba1c)i |
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nhibition of cholesterol absorption |
selective cholesterol absorption inhibitors
ezetimibe |
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if you sequester bile salts |
you cant solubilize cholester
cholesterol goes into stool
LDL goes down by 10 or 20 percent
BUT the liver makes more to "compensate" so it kind of buffers the effect in a bad way |
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remember about Welchol! |
it lowers LDL AND blood sugar |
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bile acid binding resin side effects |
bloating
may interfere with absorption of fat soluble vitamins
may interfere with absorption of digitalis, thiazides, warfarin, aspirin
can raise Tgs |
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Ezetimibe |
localizes on the brush border of intestinal epithelial cells
circulates enterohepatically
well tolerated, no effect on vitamin absorption
long biological half life
used mainly as an add on to statins
decrease heart attack and stroke |
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ezetimibe + statin |
wayyy lower LDL levels, even better than with just statin
also lowers event rate percentage |
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nicotinic acid |
decreases vldl production
decreases ldl formation and increases hepatic clearance of LDL precursors
raises HDL levels
lowers Lp(a) levels ^^^particle that has been linked to clots |
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nicotinic acid niacin |
check liver transaminases, glucose levels, lipid levels, and uric acid levels
used infrequently today
was negative for reducing cardiovascular events |
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niacin side fx |
intense flushing and pruritis
hepatic toxicity - increasing transaminases
glucose intolerance (raises blood sugar)
elevate uric acid levels
contraindicated in patients with gout
dont give niacin to patients with gout!!! |
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fibrates |
lower trigylcerides by 35-50 percent barely lower ldl ata ll
raises HDL a little
most useful in pts with elevated triglycerides or low HDL
should be avoided in pateitns with hepatic or renal dysfunction
caution with patients on statins - increases risk of rhabdomyolysis use fenofibrate if you have to add fibrate to statin |
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gemfibrozil |
fibrate
slight increase in HDL
decent degrease in TG
no change in LDL |
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fenofibrate |
fibrate
indicated for severe hypertriglyceridemia pts at risk for pancreatitis
safer than other fibrates when used with a statin
cna elevate creatinine (kidney function)
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fibrate evidence |
on background statin Rx, fibrate does not reduce CV events |
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fish oil treatment |
used to lower high TGs efficacy depends on baseline TGs
FDA approved versions for pts with baseline TG above 500
may increase ldl
can increase bleeding time and interact with warfarin!!!
often stopped prior to surgery |
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what does HMG-CoA reductase do |
converts acetate to cholesterol |
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so an HMG-CoA reductase inhibitor... (statins) |
lowers cholesterol synthesis |
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statins and diet |
statins reduce cholesterol production NOT ABSORPTION
doesn't do anything to the choelsterol you eat, just the cholesterol you make |
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statin side fx |
elevations in transaminases
hepatix toxicity related to ^^ if too much
myositis presenting as muscle pain or weakness with elevated muscle enzyme levels
recent link to increased risk of diabetes (HgA1C goes up)
can affect memory |
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statin therapy recommended in 4 groups(!!!) |
adults with clinical ASCVD (heart diseae)
adults with LDL >190 mg/dL
adults 40 to 75 years old with diabetes
adults >7.5% estimated 10 year risk of ASCVD |
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PCSK9 |
stimulates endocytosis of LDL receptors. more pcsk9 means fewer LDL receptors means more LDL floating around |
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targeting PCSK9 |
works in, like, everybody
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conclusions from lipid therapy lecture |
LDL-C strong risk factor for coronary artery disease
LDL-C can be lowered by statins, ezetimibe, pcsk9 antibodies, bile acid resins, niacin
TGs also appear to be a risk factor, though not as strong
can be lowered by fibrates, niacin, fish oil |
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PR interval normal, but HR < 60 bpm QRS normal QTc normal
Sinus bradycardia |
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brief irregular tachycardia followed by slower beats
bradycardia-tachycardia syndrome |
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no p waves evident normal width qrs HR < 50 junctional escape rhythm |
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no p waves evident widenedQRS with a bundle branch block pattern HR < 40
ventricular escape rhythm |
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PR interval: 260ms prolonged QRS normal QTc normal prolonged PR and everything else okay = 1st degree AV block |
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start with short PR interval PR interval lengthening until eventually there's a P not followed by a QRS
2nd degree Type I Mobitz type I wenkebach block |
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regular PR interval missing QRS back to normal
2nd degree AV block Mobitz Type II |
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Multiple QRS missing in a row
high grade 2nd degree type II AV block |
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P and QRS are unrelated QRS looks like L or R BBB
3rd degree AV block |
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P waves and QRS complexes are normal but HR > 100
Sinus tachycardia |
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P wave occurs earlier than expected and its shape is abnormal
Atrial Premature Beat |
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rapid sawtooth atrial activity
atrial flutter |
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chaotic atrial activity without organized p waves irregular qrs rate
atrial fibrillation |
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retrograde p waves occur with QRS
Paroxysmal Supreventricular Tachycardia (PSVT) caused by AV nodal re entry |
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shortened PR interval delta wave in the QRS
Wolf Parkinson White syndrome AKA Ventricular Pre Excitation Syndrome |
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delta wave is fusion of ventricular activation via the av node and an accessory pathway
sinus rhythm |
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APB triggers orthodromic atrioventricular re entrant tachycardia
no delta wave
signals goes backwards up the accessory path and back down through the av node in this loop |
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QRS widened because ventricles are stimulated by abnormal conduction through the accessory pathway (it's slower?)
the signal runs backwards and up through the av nodal pathway and comes back down through the accessory pathway |
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arrows are on ventricular premature beats VPBs |
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monomorphic VT |
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widening QRS complexes with a waxing and waning pattern
torsades de pointes |
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V fibrillation |
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Myocardial oxygen supply comes from |
O2 content
coronary blood flow: coronary perfusion pressure coronary vascular resistance
external compression intrinsic regulation local metabolites endothelial factors neural innervation
other answer: blood flow origin carrying capacity O2 saturation |
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myocardial oxygen demand comes from |
wall stress (PxR)/(2h)
heart rate
contractility |
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oxygen supply |
myocardial extraction of oxygen is near max at rest (about 75%)
increased supply must result from increased coronary flow - vasodilation and increased cardiac output
hemoglobin saturation with oxygen and hemoglobin level are vital to delivery of oxygen |
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oxygen supply: optimal flow external pressure |
greatest during systole
subendocardium is most vulnerable as it is adjacent to high intraventricular pressure
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oxygen supply: optimal flow internal factors |
metabolic during ischemia - cant produce atp ADP and AMP are converted to adenosine
adenosine is a potent vasodilator and is the prime mediator of vascular tone -> decreased calcium entry into cells -> relaxation/vasodilation
endothelial growth factors like nitric oxide lead to vasodilation via cGMP mechanism
increased shear stress, ACh, thrombin, platelets - NO is released to compensate and lead to vasodilation |
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the most potent endogenous vasodilator? |
NO |
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other endogenous vasodilators? |
adenosine NorEpi TXA2 |
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myocardial demand comes from |
wall stress Pr/2h
heart rate
contractility |
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why are beta blockers so useful in ischemia |
longer time in diastole (increased flow)
lower wall stress (lower demand)
lower heart rate (lower demand)
lower contractility (lower demand) |
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consequences of an epicardial coronary stenosis |
if stenoses < 70%, there is little change in blood flow at rest with exercise, the artery is able to dilate to increase flow
if stenoses70-90%, there is autodilation of the resistance vessels at rest and the flow is normal with exercise, cannot dilate further to meet the demand and there is ischemia
if the stenosis is >90%, there is maximal dilation of the resistance vessels at rest to the extent possible flow at rest may be suboptimal |
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coronary pressure falls subendocardial flow vs subepicardial flow |
the subendocardial flow decreases prior to subepicardial flow |
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consequences of ischemia the cascade |
aerobic (fatty acid metabolism) is replaced byu anaerobic (glucose metabolism)
impaired diastolic function (it takes energy to relax!)
impaired systolic function
increased LV end diastolic pressure
increased lactate, serotonin, and adenosine
local metabolites and abnormalities in ion transport lead to ECG changes and arrhythmias
activation of peripheral pain receptors from C7 to T4 |
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different effects of hypoxia pulmonary vs coronary |
lungs: hypoxic vasoconstriction (don't want to perfuse a region of lung that isn't carrying oxygen)
coronary: hypoxic vasodilation |
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when the wall motion appears abnormal, the muscle must be... |
infarcted, stunned, or hibernating |
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myocardial infarct |
no flow and no metabolically active cells |
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stunning |
acute ischemia
time of abnormalities in movement and metabolism are related to time of ischemia
perfusion is normal following ischemia
occurs following coronary bypass surgery
function returns to normal within 1 week |
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hibernating |
chronic ischemia
can result from frequent or prolonged ischemia
perfusion is usually reduced
down regulation of ATP uptake and oxygen consumption |
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viable myocardium |
ability to improve motion or metabolism if coronary flow is improved |
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ischemic conditioning
pre conditioning |
when the LAD artery of a dog is clamped repetitively for 5 minute intervals prior to prolonged occlusion, the area of infarction is less than if it is clamped without prior occlusion |
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ischemic conditioning
post conditioning |
opening balloon in infarct-related artery to transiently occluded flow after opening the occlusion
upregulation of inducible NO synthase among other proposed mecehanisms |
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ischemic cascade |
metabolic alteration
perfusion abnormalities
diastolic dysfunction
regional wall motion changes
ECG changes
angina |
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spectrum of coronary artery disease |
noninvasive tests normal: normal
fatty streak
plaque
increasing plaque
noninvasive tests abnormal: obstructive atherosclerotic plaque
plaque fissure results in thrombosis |
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anginal syndromes
normal |
patent lumen
normal endothelial function
platelet aggregation inhibited |
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anginal syndromes
stable angina |
lumen narrowed by plaque
inappropriate vasoconstriction |
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anginal syndromes
unstable angina |
biomarker negative plaque rupture platelet aggregation thrombus formation unopposed vasoconstriction |
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anginal syndromes
MI |
biomarker positive
plaque rupture platelet aggregation thrombus formation unopposed vasoconstriction |
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anginal syndromes
variant angina |
no overt plaques
intense vasospasm the spasms can slow flow |
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tests to assess presence of atherosclerosis
carotid IMT |
no radiation no contrast
thicker intimal lining = worse survival |
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tests to assess presence of atherosclerosis
coronary calcium scan |
minimal radiation no contrast
more calcium = less survival |
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tests to assess for atherosclersis
what about the stress test? |
stress tests are for obstructive plaques >70%
below 70% you wont see anything on a stress test
if you don't have symptoms, a stress test won't tell you anything
most heart attacks are NOT caused by obstructive plaques, they're caused by non-obstructive plaques that rupture |
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likelihood of acute coronary syndrome
history |
high likelihood: chest or left arm discomfort as typical symptoms worse with exertion or mental stress alleviated by nitro known CAD
intermediate: new chest or left arm discomfort >70 years old male diabetes mellitus
low: recent cocaine use probable angina (in absence of typical symptoms) |
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likelihood of acute coronary syndrome
exam |
high: mitral regurg hypotension diaphoresis pulmonary edema
intermediate: extracardiac vascular disease (bruits or PAD)
low: chest discomfort reproduced by palpation |
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likelihood of coronary syndrome
ECG |
high: new ST segment changes T wave inversions with symptoms
intermediate:fixed q waves abnormal ST/T waves or unclear duration
low: T wave flattening normal EKG |
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likelihood of acute coronary syndrome
cardiac biomarkers |
high: elevated troponin T |
|
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atypical angina symptoms |
dyspnea fatigue arm discomfort nausea diphoresis
in women, elderly, diabetics |
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syndrome X |
chest pain and abnormal stress test with normal epicardial coronary arteries
more common in women
more favorable prognosis than with coronary obstruction
may represent endothelial dysfunction or microvascular disease can perform brachial reactivity test to assess for endothelial dysfunction
may treat with nitrates, ca channel blockers, ace inhibitors, beta blockers, statins |
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unstable angina features |
symptoms at rest increasing frequency increasing duration lower threshold for symptoms biomarker negative (Troponin)
patients with unstable angina (troponin neg) or NSTEMI/STEMI (troponin pos) SHOULD NOT UNDERGO STRESS TESTING ON PRESENTATION |
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why do we perform cardiac stress tests> |
to provide an exercise prescription
to identify the etiology of a patient's symptoms (Chest discomfort or dyspnea)
to risk stratify patients with known coronary artery disease
to assess for arrhythmias with exercise |
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when NOT to perform a stress test? |
acute MI
high risk unstable angina
decompensated heart failure
uncontrolled cardia arrhythmias
AV block
acute myocarditis or pericarditis
severe aortic stenosis
severe HOCM
uncontrolled HTN
acute systemic illness - PE, Aortic dissection |
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major categories of stress testing: |
one from each group! group 1: treadmill or bike/arm ergometry adenosine or adenosine analogue dobutamine (beta 1 agonist)
group 2:ECG nuclear echo cardiac MRI PET |
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ischemic cascade AGAIN |
metabolic alteration perfusion abnormalities diastolic dysfunction regional wall motion changes ECG changes Angina |
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mechanism of imaging and the step in ischemic cascade it sees |
PET - earliest (glucose metabolism -remember the heart switches to this during ischemia)
cardiac MRI - early (perfusion)
echocardiogram - late (systolic dysfunction)
ECG - latest |
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MET |
metabolic equiv
unit of oxygen uptake in a resting state
1 MET is 3.5 ml O2/kg/min
more intense activities = more METs |
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maximal stress test |
85% of maximum predicted heart rate
maximal predicted heart rate = 220-age |
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ECG evidence of ischemia |
ST starts to drop (V4)
J point - compare 80ms after J-point to TP interval (to see baseline?) |
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non walker |
if a patient cannot exercise, one can perform pharmacologic stress test (adenosine, persantine, or dobutamine) |
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pharmacologic stress testing - adenosine |
at rest the distal arteries autodilate in the artery with the epicardial stenosis
during stress (with adenosine), the distal arterioles are already dilated so only the arterioles distal to the normal epicardial artery can dilate
at rest the flow to both septal and lateral myocardial is normal because the lateral coronary arterioles autodilate with adenosine stress, the relative flow is increased more to the septal wall because the lateral wall arterioles are already maximally vasodilated |
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sensitivity of a test |
likelihood to miss a positive (or correctly call someone as negative) |
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specificity of a test |
likelihood to wrongly label someone as positive |
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rank of tests, most sensitive/specific to least |
adenosine PET
exercise nuclear
exercise echo
exercise ECG |
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flowing blood to fibrin clot
how does it happen? |
a complex "cascade" of events converts flowing fluid blood to a solid fibrin clot |
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vessel injury... |
vasoconstriction (reduce blood flow)
coagulation cascade (thrombin -> fibrin -> stable hemostatic plug)
collagen exposure -> platelet activation -> platelet aggregation -> primary hemostatic plug -> stable hemostatic plug
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vasoconstriction |
slows the flow of blood and helps to limit blood loss
mediated by: local controls (thrombaxane vasoconstricts) systemic control (epi by adrenal glands stimulates) |
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the coagulation cascade bullet points |
blood has more than a dozen clotting factors
coagulation involves a biological amplification system
sequential activation of a series of proenzymes or inactive precurosr proteins to active enzymes, resulting in significant amplification
culminates in the generation of thrombin
thrombin converts soluble plasma fibrinogen into fibrin
fibrin converts the unstable primary platelet plug to a more stable, firm hemostatic plug |
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pathwayway from vessel injury coagulation cascade |
VIIa converts tissue factor to TF VIIa
TF VIIa, VIIIA IXa, and V convert X to Xa Va
Xa Va convert prothrombin to thrombin
thrombin turns fibrinogen to a fibrin monomer
fibrin monomers polymerize
fibrin polymers are modified by XIIIa to be stable fibrin |
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control of the clotting cascade extrinsic pathway |
damage to tissue outside the vessel
tissue thromboplastin inactive factor x to active factor x
active factor x turns prothrombin to thrombin
thrombin turns fibrinogen to fibrin
XIII turns fibrin to blood clot |
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control of the clotting cascade
intrinsic pathway |
damage to the blood vessel
cascade of clotting factors turns inactive factor X to activated factor X
activated factor X turns prothrombin to thrombin
thrombin turns fibrinogen to fibrin
factor XIII turns fibrin to blood clotq |
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target sites in the coagulation cascade |
TF
Xa Va
prothrombin
thrombin
fibrinogen
the stable fibrin |
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initiation of the clotting cascade |
coagulation is initiated by the interaction of membrane bound TF exposed by vascular injury with plasma factor VIIa
TF-VIIa activates factor IX and factor X
Factor Xa without its cofactor forms small amounts of thrombin and prothrombin
^insufficient to initiate significant fibrin polymerization activates several coenzymes: factor V, factor VIII, platelets, and factor VI
the initiation pathway is rapidly inactivated by TFPI (tissue factor pathway inhibitor) |
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after TFPI inactivates initiation pathway |
thrombin generation is now dependent on the traditional intrinsic pathway which has been primed by the small amount of thrombin generated during initiation |
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amplification of the clotting cascade |
thrombin generation is now dependent on the traditional intrinsic pathway -> primed by thrombin generated during initiation
in the amplification phase, intrinsice Xase activates sufficient Xa
Xa in combination with Va, PL, and Ca2+ leads to explosive generation of thrombin which acts on fibrinogen to form the fibrin clot |
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intrinsic Xase VIIIa-IXa complex |
greatly amplifies Xa production from X |
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prothrombinase complex |
Xa, Va, PL, and Ca2+ leads to explosive generation of thrombin from prothrombin |
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thrombin activates |
XI, V, XIII
thrombin also cleaves VIII from its carrier so that it cant help[ turn X into Xa-Va |
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thrombin activation of XIII |
turns XIII into XIIIa and XIIIa turns fibrin polymer into stable fibrin |
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formation and stabilization of fibrin |
thrombin hydrolyzes fibrinogen forming fibrin monomers
calcium acts like a glue to hold the fibrin monomers together to form a loose insoluble fibrin polymer
factor XIII is also activated by thrombin
activated factor XIII stabilizes the fibrin polymers
the stabilized meshwork of fibrin fibers traps erythrocytes, thus forming a clot that stops the flow of blood |
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coagulation and vitamin k |
activity of factors II, VII, IX, and X - as well as protein C and S - is dependent upon vitamin K
vitamin k carboxylates a number of terminal glutamic acid residues on each of these molecules
vitam k comes from green vegetables and bacterial synthesis in the gut
vitamin k deficiency is caused by por diet, sever liver disease, malabsorption, or inhibition by VKA (warfarin) |
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physiological limitations of blood coagulation |
unchecked blood coagulation would lead to dangerous occlusion of blood vessels if protective mechanisms were not in place
coagulation factor inhibitors blood flow fibrinolysis |
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coagulation factor inhibitors |
effect of thrombin has to be limited to the site of injury
TFPI is synthesized in endothelial cells and present in plasma and platelets. it inhibits Xa and VIIa and TF
antithrombin is a circulating plasma portease inhibitor neutralizing many enzymes in the clotting cascade (especially thrombin and factor Xa)
heparin potentiates antithrombins action markedly heparin is used int he treatment and prevention of clotting disorders |
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Protein C and Protein S |
inhibitors of coagulation cofactors V and VIII (inactivating prothrombinase and intrinsic Xase
Vitamn K dependent proteins
as clot formation progresses, thrombin binds to thrombomodulin causing a confomrational change in thrombin that activates protein C
then protein C destroys factors VA and VIIIa, preventing further thrombin generation
activation of protein C is enhanced by protein S
activated protein C also enhances fibrinolysis |
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fibrinolysis |
a normal hemostatic response to vascular injury
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fibrinolysis plasminogen |
is converted to plasmin by activators from th e vessel wall or from the tissues
the most important route follows the release of tissue plasminogen activator (tPA) from the endothelial cells
APC destroys plasma inhibitors of tPA, thus stimulating fibrinolysis |
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fibrinolysis plasmin |
pjlasmin is capable of digesting fibrinogen, fibrin, factors V and VIII and many other proteins
cleavage of peptide bonds in fibrin and fibrinogen produces a variety of split (degradation) products |
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fibrinolytics agents |
recombinant tPA was synthesized using recombinant DNA technology
the bacterial agent streptokinase is produced by hemolytic streptococci - forms a complex with plasminogen - and converts plasminogen to plasmin
Urokinase is a tPA initially isolated from human urine |
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endothelial cells |
ECs have an active role in the maintenance of vascular integrity
provoides the basement membrane that separates collagen, elastin, fibronectin from the circulating blood
loss or damage to the endothelium results in both hemorrhage and activation of the clotting casade
ECs also have a potent inhibitory influence on the hemostatic response through the synthesis of NO, prostacyclin (PGI2), and the endonucleotidase CD39
In contrast, endothelins can activate fibrinolysis via the release of tPA |
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things endothelial cells produce |
Tissue Factor initiates coagulation
prostacyclin and nitric oxide vasodilation/inhibition of platelet aggregation
vWF platelet collagen adhesion, complex with factor VIII
antithrombin/TFPI/Protein S, Binding protein C, Actation of protein C inhibition of blood coagulation
tPA fibrinolysis |
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general causes of thrombosis |
increased level of procoagulants
decreased levels of anticoagulants
abnormal fibrinolysis |
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inherited causes of thrombosis
inreased levels of procoagulants |
factor V Leiden Activaed protein C resistance
Prothrombin mutation
hyper homocysteinemia
factor VIII, IX, XI, VII, VWF
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inherited causes of thrombosis
decreased levels of anticoagulants |
antithrombin
protein c
protein s
thrombomodulin
tfpi |
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inherited causes of thrombosis
abnormal fibrinolysis |
plasminogen deficiency
decreased tPA
increased PAI1
elevated TAFI |
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platelets |
produced in bome marry by fragmentation of the cytoplasm in megakaryocytes
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thrombopoietin |
a major regulator of platelet production, produced in the l/iver and kidneys
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normal platelet life span |
7 to 10 days |
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platelets create interface etween |
hemostasis, innate immunity, and inflammation in atherosclerosis |
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GP IIb/IIIa |
fibrinogen receptor
makes the platelets stick together |
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platelets at work |
damage to the vascular endothelium results in recruitment of platelets which aggregate at the site, forming the primary hemostatic plug
through the processes of adhesion, aggregation, and secretion, platelets successfully coalesce to complete the formation of the primary hemostatic plug |
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platelets and inflammation |
enhanced expression of cell adhesion molecules (p-selectin and e-selectin) in a systemic inflammatory environment
platelets then secrete cytokines, chemokines, growth factors, adhesion molecules, and coagulation factors
platelets bind to circulating leukocytes, dendritic cells, and progenitor cells producing coaggregates that support further leukocyte activation, adhesion, and transmigration |
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is increased platelet activity important? |
platelet hyper-reactivity following ACS predicts 5 year outcomes
hyper reactivity = more patients dying or having cardiac events |
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anti platelet therapy good and bad news |
good news - it decreases cardiovascular events
bad news - it increases the risk of major bleeding |
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thrombosis versus bleeding in platelet therapy? |
platelet activation heart attacks strokes blood clots
platelet inhibition major bleeding transfusion reoperation |
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virchow's triad |
endothelial injury abnormal blood flow hypercoagulability
all three together can cause thrombosis |
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etiology of acute MI |
coronary atherosclerosis
coronary thrombosis
myocardial necrosis |
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plaque vulnerability factors |
size of atheromatous core
thickness of fibrous cap
inflammation and repair of fibrous cap (macrophage activation) |
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acute coronary syndromes |
unstable angina
non STEMI
STEMI |
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acute MI pathologic phases |
ischemic insult
necrosis
healing
scarring |
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infarct size depends on |
distribution of coronary artery
point of total occlusion |
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chest pain in acute MI |
retrosternal, left side of chest, ulnar side of left arm
pressure, squeezing, constricting >20 minutes, persistent shortness of breath, diaphoresis |
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MI triggers |
no trigger (51.1%)
emotional upset (18.4%)
moderate physical activity (14.1%)
heavy physical activity (8.7%)
lack of sleep, overeating, other (7.7%) |
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when do the most MIs happen? |
Early in the morning |
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acute anterior wall MI
wide QRS and elevated ST? |
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acute anterior wall MI |
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acute anterior wall MI
see ST elevations start in V1
see reciprocal ST depressions in I, II, III, aVF |
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acute inferior wall MI
ST elevations in II, III, aVF
ST reciprocal depressions in V1, V2, V3 |
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can't really see ST elevationsin II, III, aVF
but you DO see the reciprocal ST depressions in V2 and V3
acute inferior wall MI |
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diagnostic criteria of abnormal Q waves |
width of q wave > 0.04 sec (40 msec)
depth of Q wave >25% of R wave
width is more importantw |
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hat causes pathologic q waves? |
necrosis |
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evolutionary EKG changes of acute MI |
acute ST elevation
Hours ST elevation, decreased R wave, Q wave begins
Days 1-2 T wave inversion Q wave deepens
Days later ST normalizes T wave inverted
Weeks later ST and T normal Q wave persists |
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cardiac markers
yellow is CK-MB
pink is Troponin
green is LDH (not used anymore)
you can see that the troponin level starts earliest and spikes the highest. it also lasts longer.
CK-MB starts a bit after troponin but has a steeper slope and peaks sooner. |
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myocardial damage left ventricular dysfunction |
decreased ejection fraction
elevated LV volume and pressure |
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myocardial damage
decreased ejection fraction |
leads to decreased stroke volume and cardiac output
systemic hypoperfusion |
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myocardial damage
elevated LV volume and pressure |
elevated left atrial and pulmonary capillary pressures
pulmonary congestion |
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MI complications
LV dysfunction |
pump failure
heart failure - rales
pulmonary edema
cardiogenic shock |
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MI complications extent of LV dysfunction |
depends on degree of necrosis |
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MI complications myocardial healing |
Ventricular septal defect
ventricular free wall rupture
aneurysm formation |
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MI complications involvement of papillary muscle |
mitral regurgitation |
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MI complications involvement of conduction system |
heart block av node, bundle branch system
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MI complications ventricular arrhythmias |
secondary ischemia and scarring |
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more MI complications |
pericarditis
postinfarction ischemia |
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MI treatment |
open the occluded coronary artery
salvage/preserve threatened myocardium
limit the size of the infarction |
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pathophysiology of STEMI |
generally caused by a completely occlusive thrombus in a coronary artery
results from stabilization of platelet aggregates at sites of plaque rupture by fibrin mesh
treated pharmacologically via thrombolysis and platelet antagonists
cather treatments are balloons and stents |
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thrombolysis |
plasminogen is activated to plasmin
plasmin attacks fibrin which makes up the thrombus and fibrinogen in the circulation
creates fibrin degradation products |
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streptokinase |
plasminogen activator
streptokinase binds with plasminogen to make the plasminogen streptokinase activator complex wihich converts plasminogen to plasmin
plasmin converts fibrin or fibrinogen to fibrin degredation products
50% successful reperfusion |
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tissue plasminogen activator |
produced by normal endothelia
tPA is a serine protease
it works best whhen already in contact with fibrin
it converts plasminogen to plasmin
plasmin converts fibrin and fibrinogen to fibrin degradation products
less fibrinogen depletion and better targeted at fibrin
75% successful reperfusion |
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tissue plasminogen activator
fibrin specificity |
kringle domains allow tPA to recognize and bind to fibrin
higher affinity for fibrin-bound plasminogen than for free circulating plasminogen
dissolves clots better than streptokinase
has a half life of 5 minutes given as a bolus plus a 90 min infusion |
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tPA mutant forms |
TNKase half life is 5 to 7 x that of tPA can give in a single bolus has even better fibrin specificity
retaplase (rPA) half life is 2-3x tPA given as a double bolus |
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complicationsof thrombolysis |
intracranial hemorrhage increased risk over 65 years old, low body weight, severe hypertension
contraindications are prior intracranial hemorrhage, active bleeding, recent trauma
reocclusion is another complication give thrombin antagonists and platelet inhibitor with the drug |
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indications for thrombolysis or acute PTCA/Stent |
chest pain consistent with acute mI
EKG changes ST segment elevation > 1mm new bundle branch block
time from onset of symptoms < 12 hours |
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principles of reperfusion
determinants of survival |
rapidity of reperfusion
magnitude of restoration of flow
persistence of flow
major complications are bleeding and reinfarction |
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pharmacology for thrombolysis therapy of MI |
platelet antagonist aspirin clopidogrel/prasugrel IIb/IIIa inhibitor
thrombin inhibitor bivalirudin, heparin
beta blocker
ACE inhibitor |
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ADP P2y12 receptor antagonists thienopyridines |
require metabolic actiavtion via CYP2C19 pathway |
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ADP P2Y12 receptor antagonists
thienopyridines
clopidogrel (plavix) |
4-8 h for peak onset of action
maximum platelet inhibition of 40-50%
many nonresponders due to genetic polymorphisms |
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ADP P2Y12 receptor antagonists
thienopyridines
prasugrel (effient) |
faster onset of action than clopidogrel, works within 15m
more platelet inhibition than clopidogrel, 80% at one hour
greater efficacy and increasing vleeding vs clopidogrel
useful for STEMI |
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ADP P2Y12 receptor antagonists
cyclopentyl-trazalo pyrimidine |
do not require activation |
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ADP P2Y12 receptor antagonists
cycoplentyl-trazalo pyrmidine
ticagrelor (brilinta) |
onset of action similar to prasugrrel
degree of platelet inhibition slightly greater than prasugrel
greater efficacy and increased bleeding vs clopidogrel
useful in STEMI |
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Pharmacologic therapy post MI survival benefit as acute therapy and chronic therapy |
beta blockers ACE inhibitors aspirin |
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pharmacologic therapy post MI NO survival benefit as acute therapy or chronic therapy |
nitrates
magnesium
calcium blockers |
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normal medications for MI |
anti-ischemic: beta blocker nitrates calcium channel blocker
general measures: pain control (morphine) supplemental O2 if needed
antithrombotic-antiplatelet aspirin clopidogrel GP IIb/IIIa inhibitor
antithrombotic-anticoagulant (use one) LMWH unfractionated intravenous heparin fondaparinux bivalirudin
adjunctive: statin ACE inhibitor |
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single leading killer in the western world |
coronary artery disease |
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angina pectoris |
discomfort or pain in the chest
occurs when coronary blood flow is inadequate to supply the oxygen requirements of the heart |
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stable angina |
no change in frequency, severity, duration, or precipitating factors in the previous 60 days
generally occurs with exertion and relieved by rest
good prognosis |
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pathyphysiology of stable angina |
one or more severe narrowings in a large epicardial coronary artery
generally due to ahtersclerosis without superimposed thrombus |
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stable angina |
severely narrowed l umen
thick fibrous cap
distant lipid core |
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left is stable angina
right is unstable angina or vulnerable |
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stable angina treatment goals |
relieve discomfort with medications that improve oxygen supply and/or reduce oxygen demand of the heart
revascularization by angioplasty or bypass surgery indicated if medical therapy fails
risk stratificataion, prevent progression of disease |
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useful medications for stable angina |
beta adrenergic receptor antagonists
calcium channel blockers
nitrates
aspirin
statins
ranolazine for resistant angina on meds |
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vasospastic angina |
can occur at rest or on exertion
may be associated with atherosclerosis
treated with nitrates and calcium channel blockers
statins may treat underlying endothelial dysfunction + aspirin
DONT use beta blockers |
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unstable angina |
angina increasing in frequency, intensity, or duration
angina at rest
transient ecg changes
high risk of myocardial infarction and death in the ensuing months
usually a ruptured plaque -> thrombus in the vessel, not 100% occluded |
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pathphysiology of unstable angina |
ruptured atherosclerotic plaque
partially occluding thrombus in lumen of large epicardial coronary artery |
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coronary thrombosis |
plaque ruptures or fissures at high mechanical stress points
fibrous cap may thin due to monocyte production of proteases, which may chemically digest the plaque cap |
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coronary thrombosis fibrous cap rupture |
underlying tissue is exposed, clotting mechanisms are activated
thrombus forms
thrombus may be non occlusive and eventually be incorporated into the atherosclerotic plaque. |
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coronary thrombosis partially occlusive |
leads to the acute coronary syndromes, unstable angina or nonSTEMI
unstable angina = no enzymes
with enzymes its non STEMI |
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coronary thrombosis totally occlusive |
leads to the most common presentation of acute MI
sever chest pain
ST segment elevations |
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unstable angina treatment goals |
relieve discomfort with medications that improve oxygen supply and/or reduce oxygen demand of the heart
prevent myocardial infarction and death
aggressive revascularization |
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useful medications in unstable angina |
beta adrenergic receptor antagonists
calcium channel blockers
nitrates
aspirin
heparin - unfractionated and low molecular weight
newer anti platelet agents - GPIIb/IIIa receptor antagonists and thienopyridines
Statins |
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all antianginal agents work by either... |
increasing O2 supply or decreasing O2 demand |
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determinants of myocardial O2 supply |
oxygen carrying capacity (hemoglobin)
coronary arteriolar resistance
duration of diastole (heart feeds in diastole)
intra-coronary pressure gradients atherosclerosis vasospasm |
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myocardial O2 demand |
wall stress = (PxR)/(2h)
p = intraventricular pressure (vascular resistance) r = ventricular radius (volume) h = wall thickness
heart rate contractility
surrogate for O2 demand is systolic PxHR |
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antianginal medications |
first line: nitrates calcium channel blockers beta blockers
second line: ranolazine |
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nitrates: mechanism of action |
venodilation and arteriodilation, but more venous
reduction in preload, decrease in blood return to the heart, heart size decreases
reduction in blood pressure and therefore in afterload
attentuation of coronary vasospasm
improved collateral blood flow |
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nitrate effects in angina |
decreased myocardial oxygen requirement by decreasing wall stress both P and R
possible improved oxygen delivery
decrease P, decrease R, then you decrease O2 requirement |
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nitrates: cellular mechanisms |
enzymatic degradation to nitric oxide
activation of intracellular guanylyl cycloase in smooth muscle by NO
increase cGMP
dephosphorylation of myosin light chain phosphate, inactivating myosin-actin interaction leading to vasodilation
effects only on smooth muscle, no effects on cardiac or skeletal muscle |
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nitrate mechanism |
nitrates become ONO2
reduced to NO2
reduced to NO
NO turns on guanylyl cyclase
GTP+ guanalyl cyclase makes cGMP
cGMP causes vasodilation |
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nitrate mechanism contd |
nitric oxide activates guanylyl cyclase
gtp converted to cGMP by guanylyl cyclase
myosin light chain has a phosphate on it that allows it to bind to actin causing vasoconstriction
when the phosphate is removed by cGMP, the myosin light chain can't bind actin and the vessel relaxes |
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phosphodiesterase
viagra? |
phosphodiesterase breaks cGMP down to GMP
viagra (and any other phosphodiesterase inhibitor) will keep that from happening, meaning you have too much cGMP and too much relaxation |
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adverse effects of nitrates |
headache orthostatic hypotension reflex tachycardia due to vasodilation
tolerance to nitrates can develop and they'll stop working
rebound due to nitrate withdrawal |
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possible mechanisms for tolerance to nitrates |
sulfhydryl group depletion
salt and water retention
increased free radicals that degrade NO |
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nitrates have to get to circulation without |
going to the liver first. thats why theyre put sublingual usually |
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calcium channel blockers mechanism of action |
arterial vasodilation more than venodilation lowers blood pressure
potent coronary artery dilation drugs of choice for coronary vasospasm
negative inotropy
negative chronotropy |
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calcium channel blockers cellular mechanisms |
blockade of voltage dependent L type calcium channels
the L type calcium channel is the dominant calcium channel
it has several receptors and the different classes of drugs bind to different receptors
reduction in transmembrane calcium flux
skeletal muscle isn't depressed by the calcium channel blockers because it uses intracellular pools of calcium to support excitation-contraction coupling and does not require much transmembrane calcium influx |
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blocking the calcium channel in diferent places... |
on vascular smooth muscle it results in vasodilation
on the myocardium results in reduced inotropy
on the SA node and AV node it results in slowed conduction
on the GI tract it results in decreased peristalsis |
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calcium channel blocker effects in angina |
increases O2 supply relieves vasospasm some prolong diastole
decreases O2 demand decreased inotropy vasodilation decreases arterial pressure (lowers wall stress) some classes slow the heart rate |
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classes of calcium antagonists |
first gen dihydropyridines
second gen dihydropyridines
phenylalkamines
modified benzothiazepines |
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calcium channel blocker first gen dihydropyridine nifedipine |
potent vasodilator greater effect on vascular smooth muscle than cardiac muscle
may cause reflex tachycardia so it should be used with a beta blocker
negative inotrope (usually not a problem because of increased CO due to vasodilation)
short acting preparation removed from market due to risk of MI and stroke secondary to hypotension
long acting preparations |
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nifedipine adverse effects |
headaches
dizziness
lower extremity edema (diuretics dont work for this kind of edema)
flushing |
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verapamil |
ca channel blocker
potent negative chronotrope
negative inotrope
systemic and coronary vasodilator
useful as an antiarrhythmic agent for supraventricular tachycardias |
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verapamil adverse effects |
headache
flushing
lower extremity edeme
constipation (greater effect on peristalsis)
excessive sinus bradycardia and AV block
CHF exacerbation (because of decreased inotropy)
increases digoxin blood levels |
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diltiazem |
ca channel blocker
less potent vasodilator than nifedipine
less potent negative chronotrope than verapamil
negative inotrope
iv form useful for controlling ventricular rate in a fib (slows the av node) |
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diltiazem adverse effects |
headache
flushing
lower extremity edema
excessive sinus bradycardia and AV block
CHF exacerbation |
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Amlodipine |
safest ca channel blocker in patients with CHF
well tolerated
once a day |
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beta receptor subtypes
beta 1 |
predominate in the heart
stimulation results in increased heart rate, av conduction, and contractility |
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beta receptor subtypes
beta 2 |
predominate in the lungs and liver
stimulation results in bronchodilation, vasodilation, and glycogenolysis |
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beta blocker mechanism of action |
negative chronotrope, negative inotrope
lower blood pressure
increase duration of diastole
attenuate exercise mediated increases in contractility and heart rate
anti arrhythmic effect suppresses lethal ventricular arrhythmias
survival benefit in patients post MI and with compensated CHF |
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beta 1 selective beta blockers |
atenolol
metoprolol |
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adverse beta blocker effects |
bronchocnostriction
exacerbation of chf
impotence
depression
excessive sinus bradycardia and av block
masking of hypoglycemia in diabetics |
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ranolazine (ranexa) |
first new class of antianginals in more than 20 years
indicated for patients who continue to have angina on standard antianginals or for those who cannot tolerate standard antianginals
works by blocking the late I(Na) channel
may be used in pts with low heart rate or low bp, CHF, DM, or asthma |
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origin of late I(Na) |
during the plateau phase of the AP, a small proportion of Na channels either do not close, or close and then reopen
these late channel openings permit a sustained Na current to enter myocytes during systole |
|
|
myocardial ischemia and late I(Na) |
it causes enhnaced late I(Na)
enhanced late I(Na) appears to be a major contributor to increased intracellular Na during ischemia |
|
|
role of altered ion currents in adverse consequences of myocardial ischemia |
increase in late I(Na) causes too much sodium entry into the cell which causes too much Ca in the cell
too much calcium causes electrical instability and mechanical dysfunction
afterpotentials APD arrhythmias (VT)
abnormal contraction and relaxation increased diastolic tension |
|
|
sustained contractoin of ischemic tissue during diastole |
increases myocardial oxygen consumption
compresses intramural small vessels
reduces myocardial blood flow
overall it exacerbates ischemia |
|
|
ranolazine mechanism of actionin |
creased intracellular calcium does not allow normal LV relaxation
leads to increased O2 consumption and potential compression of hte vascular supply
ranolazine blocks the late I(Na) channels and therefore prevents intracellular calcium overload
pts experience less chest pain and improved exercise duration |
|
|
strategies in the medical treatment of stable angina
|
beta blockers are the first line
pts should be given a bottle of sublingual nitro and instructed on use
calcium channel blockers used if beta blockers are contraindicated or not tolerated may be added if angina persists or to treat HTN
rannolazine for persistent angina
risk stratificatoin (high risk -> cath)
plus aspirin and a statin |
|
|
strategies in the medical treatment of unstable angina |
hospitalization
treatment of angina, usually with nitrates sublingual or IV often give beta blockers oral or IV
treatment of underlying ruptured plaque with thrombus - aspirin plavix statin antithrombin like heparin other antiplatelet agents
risk stratification with cardiac cath |
|
|
definition of thrombosis |
formation of intra-vascular blood clot |
|
|
thrombosis clinical significance |
acute coronary syndrome
embolic stroke
pulmonary embolism |
|
|
underlying cause of thrombosis |
abnormality of normal hemostatic mechanism |
|
|
thrombosis vs hemostasis
thrombosis |
intravascular blood clot
compromises blood vessel lumen and impedes blood flow
|
|
|
thrombosis vs hemostasis
hemostasis |
extra vascular blood clot located on external surface of blood vessels
prevents bleeding after vascular injury |
|
|
thrombosis pathophysiology |
endothelial injury
platelet activation
coagulation cascade
stasis |
|
|
endothelial injury... |
exposes underlying collagen
releases tissue factor
impairs endothelial cell production and release of anti-thrombotic factors: NO, prostacyclin, tissue plasminogen activator, tissue factor pathway inhibitor |
|
|
platelet activation |
initiated by collagen
shape change and degranulation
platelet delivers drugs
recruit of circulating platelets by ADP
glycoprotein IIb/IIIa receptor stimulation is the final common pathway of platelet aggregation |
|
|
things platelets deliver on their own |
adenosine diphosphate
factor V
platelet factor 4
platelet derived growth factor
tgf beta
thromboxane A2
serotonin |
|
|
Glycoprotein IIb/IIIa receptor stimulation on platelet |
its normally inside the platelet
it sticks out when activated
they can attach to fibrinogen and attach to each other through the fibrinogen |
|
|
coagulation cascade simplified schema |
endothelial injury leads to TF release
TF activates factor VII
factor VIIa complex activates factor X
Factor Xa+Va (prothrombinase complex) makes thrombin IIa |
|
|
modulation of thrombin activity
increased |
Xa+Va leads to thrombin formation
thrombin converts V to Va to Thrombin generation (positive feedback loop) |
|
|
modulation of thrombin activity
decreased |
circulating proteins C and S inactivate Va, leads to reduced thrombin formation
circulating anti-thrombin III directly inactivates thrombin |
|
|
drug classes used to prevent thrombosis |
anti-platelet agents
anticoagulants |
|
|
antiplatelet agents |
salicylates
ADP receptor antagonists
cAMP agonists
Thrombin receptor antagonists
glycoprotein IIB/IIIa antagonists |
|
|
salicylates (aspirin) |
weak platelet antagonists
irreversible acetylation and inactivation of cyclo-oxygenase blocks TxA2 production
indicated for MI and secondary prevention of MI and stroke prevention in low risk a fib
main side effect is GI bleeding
doses of ASA as low as 75mg every other day impair platelet function |
|
|
ADP receptor antagonists |
ticlopidine clopidogrel prasugrel ticagrelor
|
|
|
what adp receptor antagonists do |
more potent than ASA
block the P2Y12 receptor to prevent recruitment of circu lating platelets
clinical effects are irreversible for days
thienopyridines are prodrugs metabolized by cytochrome p450 to the active compound
potential for drug drug interactions
CYP2C19 reduced function allele associated with reduced response to clopidogrel |
|
|
clinical use of ADP antagonists |
indicated for stroke prevention in patients with prior stroke or TIA
indicated for a year after acute coronary syndrome
2-4 week course post bare metal stent
prolonged course (possibly for life) after implantation of drug eluting stents |
|
|
cAMP antagonists
dipyridamole |
inhibits uptake of adenosine by platelts, endothelial cells, and erythrocytes increasing local adenosine levels leading to platelet adenylate cyclase activation
indicated for stroke prevention in patients with normal sinus rhythm
vasodilator may cause coronary steal |
|
|
cAMP antagonists
cilostazol |
inhibits phosphodiesterase type 3
indicated as a vasodilator in vascular disease
contraindicated in heart failure |
|
|
thrombin receptor antagonists
vorapaxar |
approved by fda in may 2014 for secondary prevention post MI
increased risk of intracranial hemorrhage in patients iwth prior stroke |
|
|
glycoprotein IIB/IIIa receptor antagonists |
most potent platelet antagonists available
only available in IV form
used for treatment of acute coronary syndromes
abciximab - chimeric human/mouse FAB fragment derived from a monoclonal antibody
tirofiban and eptifibatide - small molecule short acting specific blockers
main side effect = excessive bleeding |
|
|
antiplatelet medications
aspirin |
PO
indicated for ACS treatment and prevention, low risk stroke prevention in Afib |
|
|
antiplatelet medications
ADP receptor antagonist |
PO
acs, post stent |
|
|
anti platelet medications
cAMP antagonist |
PO
stroke prevention in NSR, vascular dis |
|
|
anti platelet medicataions
PAR-1 antagonist
|
PO
secondary prevention Post-MI |
|
|
anti platelet medications
GPIIBIII antagonist |
IV
treatment of ACS |
|
|
anticoagulants |
warfarin
unfractionated heparin
low molecular weight heparins
Xa inhibitors
direct thrombin inhibitors |
|
|
warfarin |
oral anticoagulant indicated for chronic use
inhibits synthesis of vitamin K dependent clotting factors II, VII, IX, and X
inhibits synthesis of proteins C and S |
|
|
indicationsfor warfarin therapy |
mechanical heart valve prosthesis afib (stroke) pulmonary embolus (secondary prevention) DVT (secondary prevention) recent anterior wall myocardial infarction |
|
|
disadvantages of warfarin |
slow onset (2 days of treatment to get effect)
requires monitoring of blood work
interacts with drugs and foods
bleeding
hemorrhagic skin necrosis
teratogenic (birth defects) |
|
|
warfarin reversal |
oral vitamin K (may lead to prolonged resistance to warfarin)
IV vitamin K low dose for temprary reversal high dose for anaphylaxis
iv clotting factors |
|
|
Noval Oral Anticoagulants NOACs |
approved by FDA for stroke prevention in setting of non valvular a fib and for prophylaxis and treatment of dvt
rapid onset of action no monitoring needed no interaction with food
safer than warfarin
NO REVERSAL AGENTS
more expensive |
|
|
list of NOACs |
dabigatran direct thrombin inhibitor
rivaroxaban xa inhibitor
apixaban Xa inhibitor
edoxaban Xa inhibitor |
|
|
unfractionated heparin |
mixture of sulfated mucopolysaccharides derived for porcine intestinal mucosa and bovine lung
binds to and activates antithrombin III
heparin-antithrombin III complex inhibits thrombin, inhibits Xa, and enhnaces activity of TFPI
can be reversed by protamine |
|
|
indications for heparin therapy |
anticoagulation during initiation of warfarin therapy
acute coronary syndromes
cardiac cath, cardiac surg, and vascular surge
SQ heparin indicated for prophylaxes of venous thrombo-embolic disease |
|
|
disadvantages of heparin therapy |
non specific binding of heparin to plasma proteinsresults in variable dose response
bleeding
osteoporosis
rebound hypercoagulable period
heparin induced thrombocytopenia |
|
|
effect of saccharide chain length on anti Xa: anti IIa ratio` |
12 sugars on ATIII lets thrombin bind
only the 5 sugars ATIII is bound to lets Xa bind to it |
|
|
low molecular weight heparin |
same mechanism as heparin
less protein binding, more reliable anticoagulant effect
subq administration
fewer side effects |
|
|
Xa inhibitors |
fondaparinux
rivaroxaban
edoxaban |
|
|
Xa inhibitors
fondaparinux |
synthetic penteasaccharide results in antithrombinIII mediated inhibition of XA
subq administration
indicated for prevention of dvt
may be used for therapy of acute coronary syndrome |
|
|
Xa inhibitors
rivaroxaban |
oral therapy approved nov 2011 for stroke prevention in patients with a fib |
|
|
Xa inhibitors
edoxaban |
oral therapy approved jan 2015 for stroke prevntion in patients with a fib |
|
|
Direct thrombin inhibitors |
hirudin
bivalirudin
lepirudin
agratroban
dabigatran |
|
|
direct thrombin inhibitors
hirudin |
active component of the leech salivary gland
no longer in clinical use |
|
|
direct thrombin inhibitors
bivalirudin |
specific and reversible thrombin inhibitor
used for anticoagulation during coronary intervention |
|
|
direct thrombin inhibitors
lepirudin |
IV therapy for heparin induced thrombocytopenia |
|
|
direct thrombin inhibitors
argatroban |
IV therapy for heparin induced thrombocytopenia |
|
|
direct thrombin inhibitors
dabigatran |
oral therapy for smoke prevention in pts with a fib |
|
|
hirudin vs bivalirudin
hirudin |
irreversible
recombinant DNA
65 Amino acids
half life is 1.3-3 hrs |
|
|
hirudin vs bivalirudin
bivalirudin |
reversible
peptide analog
20 amino acids
half life is 25 min |
|
|
anticoagulant medications
warfarin |
po
stroke prevention in Afib
dvt/pe treatment
mechanical heart valves
recent anterior wall MI |
|
|
anticoagulant medications
novel oral anticoagulants NOAC |
PO
stroke prevention in non-valvular Afib, DVT and PE treatment |
|
|
anticoagulant medications
unfractionated heparin |
IV
DVT and PE treatment
bridge to warfarin
ACS
coronary cath
inpatient Afib |
|
|
anticoagulant medications
unfractionated heparin SC |
Subq
dvt prevention |
|
|
anticoagulant medications
low molecular weight heparin |
subq
treatment of ACS
bridge to warfarin
treatment of dvt/pe |
|
|
anticoagulant medications
Xa inhibitors |
subq
treatment of dvt/pe
ACS |
|
|
anticoagulant medications
direct thrombin inhibitors |
IV
ACS and for heparin induced thrombocytopenia |
|
|
fibrinolytics |
clot busters
convert plasminogen to plasmin
plasmin cleaves fibrin to break clots |
|
|
indications for fibrinolytic therapy |
acute MI only
not effective in unstable angina
chest pain less than 6 hrs in duration
ST elevation in 2 contingous limb or precordal leads
new LBBB |
|
|
contraindications to thrombolytic therapy |
altered consciousness
active internal bleeding
known previous hemorrhageic CVA
trauma or major surgery within 2 weeks
persistent BP elevation
pregnancy
suspected aortic dissection
recent head trauma |
|
|
thrombolytics do what |
convert plasminogen to plasmin
then plasmin degrades fibrin to fibrin degradation products
|
|
|
list of thrombollytics |
tPA rPA TNK streptokinase urokinase |
|
|
thrombolytics unique features
streptokinase |
may cause allergic rxn
cannot be readministered |
|
|
thrombolytics unique features
alteplase |
unmoidified human tPA
more rapid thrombolysis than Streptokinase
|
|
|
thrombolytics unique features
reteplase |
human tPA with several AA sequences deleted |
|
|
thrombolytics unique features
TNK-tPA |
greater fibrin specificity
reduced plasma clearance
lower major bleeding |
|
|
adp to atp via creatine |
creatine kinase and magnesium turn creatine-phosphate to creatine and the phosphate group gets donated to ADP to make ATP |
|
|
muscle fiber types type1 |
slow twitch
oxidative aerobic metabolism, fatigue resistant, red, rich in mitochondria |
|
|
muscle fiber types type IIB |
fast twitch
glycolytic anaerobic metabolism, fatigable, white |
|
|
muscle fiber types
typeIIA |
intermediate between I and IIB, oxidative and glycolytic metabolism |
|
|
response to demand for oxygenated blood during exercise |
increase in oxygen extrtaction from blood in working muscles
shunting from non working muscles and heptosplanchnic beds
increase in cardiac output (major response) 4x cardiac output (5 L/min to 20 L/min) 300% increase in HR |
|
|
Systolic and diastolic blood pressure response to exericse |
systolic pressure goes up a little
diastolic pressure mostly stays the same |
|
|
cardiac output formula |
CO = HR x SV |
|
|
difference in stroke volume between trained and untraines athletes |
higher resting and peak stroke volume among trained athletes |
|
|
can the heart extract more oxygen with exercise? |
no
peripheral muscle can, but myocytes are always extracting oxygen at near maximal levels
increases in cardiac cell oxygen demand must be met entirely by incrasing coronary artery blood flow |
|
|
myocardial oxygen consumption during exercise increases in direct relation to |
the increase in the product of systolic blood pressure and heart rate
delta MVO2 ~ delta (SBPxHR) |
|
|
Coronary blood flow vs rate pressure product |
linear relationship, as one goes up the other does too |
|
|
exercise physiology "basics" slide |
VO2 = oxygen consumption
VO2 = CO x (aortic O2 - venous O2)
VO2 max = maximum CO (HRxSV)x(AO2-VO2)
repressents fully cardiac, vascular and celular response to endurance (aerobic) exercise stress
highly reproducible, increases with training and other interventions, higher in exercise trained subjects
VO2 measured in ml/kg/min
resting VO2 is 1 Met = 2.5 ml/kg/min |
|
|
norepi and epi released from |
norepinephrine released from post ganglionic junctions
epinephrine from adrenal medulla |
|
|
beta 1 receptor |
heart
increass sinus rate increase force of contraction increase conduction via av node and hp system |
|
|
beta 2 receptor |
broncia muscle relaxation bronchial dilation arterial dilatation |
|
|
alpha 1 receptor |
arterial constriction constriction of veins |
|
|
parasymp system muscarinc receptor |
release acetylcholine at post ganglionic junction
decrease sinus rate, decrease force of contraction, decrease conduction velocity, dilate sealective arteries, constrict bronchi and increase bronchial gland secrertions |
|
|
autonomic controls of the cardiovascular response to exercise
heart rate |
suppressed at rest by parasympathetic nervous system which is gradually withdrawn at onset of exercise and HR increases to 100-110
sympathetic nervous system (beta 1) input to SA node increases HR
sympathetic system essentially modulates hr from mid to maximum exercise levels |
|
|
autonomic controls of the cardiovascular response to exercise
baroreceptor |
mechanoreceptor in aorta and carotid arteries
if it's pushed on, it inhibits SNS and activates PNS
reduction in deformation or stretch will result in activation of SNS and inhibition of PNS with increase in HR, force of contraction and arterial constriction |
|
|
how might exercise physiology compare and contrast with changes seen in prolonged standing |
with standing, initially CO falls
but then compensatory increased CO
similar to exercise, fall in parasymp and rise in symp activity
unlike exercise, which is associated with peripheral vasodilation, in prolonged standing there is peripheral vasoconstriction |
|
|
pregnancy and the heart |
peripheral resistance down
uterine blood flow up
blood volume up 40-50%
heart rate up ^^^^^^^^^^^^^^all raises cardiac output about 30%
blood pressure down or the same
pulmonary vascular resistance down
venous pressure in lower extremities up |
|
|
definition of shock |
a rude unhinging of hte machinery of life |
|
|
shock is a state resulting frfom |
inadequate perfusion of the body's cells with oxygenated blood leading to organ dysfunction |
|
|
three types of shock classification |
hypovolemic
distributive
cardiogenic |
|
|
shock probloem related to preload |
hypovolemic shock
hemorrhage anemia |
|
|
shock problem related to inotropy |
cardiogenic
CHF ACS Dysrhythmia Valve disease Cardiac tamponade |
|
|
shock problem related to afterload |
distributive
sepsis thyrotoxicosis shunt syndromes |
|
|
CVP |
central venous pressure
r side pre load |
|
|
wedge pressure |
left sided pre load |
|
|
hypovolemic shock |
low cvp low co high svr |
|
|
cardiogenic shock |
high cvp low co high svr |
|
|
distributive shock |
low cvp high co low svr |
|
|
stroke volume determinants |
preload due to venous return blood volume and venous tone
afterload due to systemic vascular resistance
contractility (inotropy) |
|
|
afterload
systemic vascular resistance |
V=IR (MAP-CVP) = CO x SVR
SVR = (MAP-CVP)/CO |
|
|
interpretation of data - shock
cardiogenic |
cvp high wedge pressure high
co/ci low
svr high |
|
|
interpretation of data - shock
distributive |
cvp down
wedgepressure down
co/ci up or down
svr down |
|
|
interpretation of data - shock
hypovolemic |
cvp down
wedge down
co/ci down
svr up |
|
|
cardiogenic shock
practical definition |
tissue hypoperfusion
low cardiac index, not due to hypovolemia, on inotropes, or off inotropes
classic shock - systolic bp <80-90 bvefore intropes/pressors or intropes/pressors requried to maintain BP
non hypotensive or pre shock low CI, high wedge pressure, high svr, preserved SBP |
|
|
cardiogenic shock complicating MI |
about 8 percent of cases of STEMI, 2.5% cases of NSTEMI
LV dysfunction is the cause in 75% usually a large anterior MI or less extensive acute injury in the context of prior MI
NSTE ACS and even unstable angina can cause shock
high mortality rate but good functional capcaity in survivors
usually develops after hospital adminssion |
|
|
myocardial infarct myocardial dysfunction
diastolic |
increase LVEDP pulmonary congestion
hypoxemia
ischemia
progressive myocardial dysfunction
death |
|
|
myocardial infarct myocardial dysfunction
systolic |
decrease cardiac output and stroke volume hypotension decrease coronary perfusion pressure ischemia
or
decrease cardiac output and stroke volume decrease systemic perfusion compensatory vasoconstriction progressive myocardial dysfunction death |
|
|
nitric oxide storm |
other paradigm for cardiogenic shock
such a high release of vasodilators that the patients SVR isn't high
High SVR, Low CO output paradigm wrong?q |
|
|
thingsto remember from shock trial |
early revasculation significant mortality benefit in individuals < 75 years old
hemodynamic parameters allow you to identify a cohort with markedly elevated risk
95% of patients had pulmonary artery catheters placed within on average 3.3 hours from admission
86% of patients had IABP placed |
|
|
shock trial
percentages due to different MI complications |
75% LV
8% MR
8% Other
5% VSR
3% RV Shock
2% rupture |
|
|
mechanical MI complications |
ventricular septal rupture
free wall rupture
papillary muscle rupture |
|
|
suspect a mechanical MI complication... |
when first non anterior MI is associated with shock
when the ECG is less impressive than the degree of hemodynamic comporomise
at any time after onset of STEMI (13 hours?) |
|
|
ventricular septal rupture as a complication of acute MI |
80% mortality
emergency surgery
percutaneous repair, maybe |
|
|
free wall rupture as a complication of acute mI |
temporary seal in some patients, but usually this is quickly fatal
as with VSR, women and older pts are at higher risk 80% mortality
emergency surgery |
|
|
typical presentation of free wall rupture or ventricular septal rupture |
electromechanical dissociation EKG looks okay but pt is doing bad
often preceded by nausea, vomiting restlessness pericardial pain abrupt bradycardia and/or hypotension, which may be transient if temporarily sealed
vsr also causes pulmonary edema, murmur |
|
|
complicationsof acute mi
papillary muscle rupture |
acute, severe mitral regurg
refractory pulmonary edema and shock
murmur may be soft (little resistance to flow)
mortality 30-60% |
|
|
shock complicating myocarditis |
most commonly viral
most common presentation includes chest pain, fever, dyspnea, palpitations, and syncope
often difficult to predict which patients will go on to develop fulminant mnyocarditis requiring hemodynamic support
higher crp (immune marker) and wider QRS in patients who eveloped fulminant myocarditis
ejection fraction slightly lower but not significantly |
|
|
fulminant myocarditis |
in largest prospective cohort of myocarditis, fulminant myocarditis was identified in 15 of 147 patients
fulminant cases were usually characterized by a distinct viral prodrome, fever, and abrupt onset of advanced heart failure symptoms |
|
|
among survivors of myocarditis with initial presentation of heart failure |
50% will develop chronic ventricular dysfunction
25% of patients will progress to transplantation or death
25% of patients will have spontaneousd improvement in their ventricular function
fulminant myocarditis has been described in 1 published series as having the best long-term prognosis with a 90% event-free survival rate |
|
|
what makes a chronic heart failure patient fall apart |
myocardial ischemia and infarction
arrhythmia
new onset atrial fibrillation
worsening valve lesions
medications (class I antiarrhythmics, calcium channel blockers) co morbid conditions like sepsis, PE, anemia, thyroid disease) |
|
|
current cardiogenic shock treatment paradigm |
hemodynamic monitoring
inotropic support
vasopressor support
IABP
hemodynamic goals: CI > 2.5, MAP > 70
if STEMI, rapid revascularization |
|
|
cardiogenic shock treatment
intropes |
choice depends on balance of adverse effects in the individual patient
dobutamine is standard but more arrhythmia than milrinone
milrinone is more vasodilation than dobutamine (not for those with hypotension refractory to norepi)
dopamine is basically an inotrope except in very high doses
levophed traditionally reserved for most severe cases of hypotension and shock |
|
|
IABP |
more flow in diastole less afterload in systole
decrease afterload by emptying the aorta |
|
|
stable atherosclerotic plaque |
|
|
ruptured atherosclerotic plaque without superimposed thrombosis |
|
|
acute coronary thrombosis complicated ruptured atherosclerotic plaque |
|
|
MI 1 day old
wave fibers with interstitial edema and early infiltrate on left
normal on right |
|
|
MI 3-4 days old
coagulative necrosis of myocytes with loss of nuclei and cross striations, dense interstitial neutrophilic infiltrate |
|
|
7 10 days old MI
nearly complete phagocytosis of necrotic myocytes by macrophages, residual viable myocardium at lower right |
|
|
acute MI 10-14 days old
granulation tissue with new vessels and collagen
collagen = blue
new vessels = red |
|
|
MI > 2 months old
necrotic myocardium is replaced by dense collagenous scar
scar = blue residual myocardium = red |
|
|
reperfusion of MI |
restoration of coronary flow via thrombolysis, PTCA, CABG
salvages the viability of reversibly injured ischemic cardiac myocytes
alters the gross and microscopic morphology of irreversibly injured cells
causes new myocardial cellular damage (reperfusion injury) |
|
|
reperfusion of myocardial infarct
contraction bands (arrow) in necrotic myocytes |
|
|
other causes of myocardial infarct (non atherosclerotic) |
coronary artery spasm coronary artery dissection coronary anomalies
common theme: present with chest pain (angina) |
|
|
coronary artery spasm |
with or without atherosclerosis smokers, alcohol withdrawal stimulants: cocaine, meth
presents with angina, key is removal of stimulating factors |
|
|
coronary artery dissection |
SCAD - spontaneous coronary artery dissection
present with angina
pre menopausal women
hypertension |
|
|
coronary artery dissection |
|
|
coronary artery dissectiont reatment |
surgery - bypass graft surgery
drug-eluting stents, thrombolytics |
|
|
coronary anomalies |
many variations in coronary anatomy
majority are clinical insignificant
found at autopsy, often clinically significant anomalies present with sudden death |
|
|
clinically significant coronary anomalies |
they're the ones that force one of the coronaries to pass between the pulmonary artery and aorta |
