Unit 1 Flashcards
Describe the functions of the CV system
- distribute dissolved gases (like O2) and nutrients
- remove metabolic waste
- maintains homeostasis (controls temp., pH, electrolytes)
Describe the series and parallel arrangement of the circulatory system, and its purposes
- right and left sides of heart arranged in series (one after another)
- systemic circulation can be parallel so that multiple organs are supplied at the same time (branching)
Describe the anatomy of the heart, including its chambers, valves, and major vessels
- epicardium: outer layer of CT and fat
- myocardium: middle layer of muscle
- endocardium: inner layer of endo cells
- pericardium surrounds entire heart; fluid filled
- four chambers: left and right atria and ventricles
- mitral valve between left atrium and ventricle
- tricuspid valve between right atrium and ventricle
- aortic valve between left ventricle and aorta
- pulmonary valve between right ventricle and pulmonary artery
- vena cava drains into right atrium
Describe the blood flow pathway through the heart
blood is oxygenated in lungs –> pulmonary vein –> left atrium –> mitral valve –> left ventricle –> aortic valve –> aorta –> body –> vena cava –> right atrium –> tricuspid valve –> right ventricle –> pulmonary valve –> pulmonary artery –> lungs to get reoxygenated
Describe the major types of blood vessels
- pulmonary vein: carry oxy blood from lungs to heart
- pulmonary artery: carry deoxy blood from right ventricle to lungs
- aorta: carry oxy blood from left ventricle to body
- vena cava: carry deoxy blood from body to right atrium
Describe the arrangement of the microcirculation
- vasculature from the first order arterioles to the venules
- site of gas, nutrient, and waste exchange
- precapillary sphincters: smooth muscle bands at junctions of arterioles and capillaries
- no smooth muscle, just endo cells and basement membrane
Describe the function of the lymphatic system
- lymph is excess interstitial fluid
- flows through lymph vessels to lymph nodes and rejoins circulatory system
- edema occurs when interstitial fluid exceeds capacity of lymphatic system
Describe the cardiac conduction system
SA node –> atria through gap junctions –> AV node (delay) –> His-Purkinje fibers
Why are arterioles so special?
- thicker than aorta and arteries
- highly innervated by autonomic nerves, circulating hormones, and local metabolites
- main site of regulation of vascular resistance by changing size of diameter
Describe the anatomy of vessels
Tunica adventitia:
- outer layer
- mostly CT with collagen and elastin
Tunia media:
- middle layer
- innervated smooth muscle
- controls diameter
Tunica intima:
- single layer of endothelial cells
What are intercalated disks?
- connect cardiac myocytes to transfer force and coordinate electrical activity
What is the relationship between pressure, flow, and resistance in the circulatory system?
- Flow is volume per unit time (Q); constant throughout system and equal to CO in CV system
Flow = Velocity*Cross-sectional Area AND Flow = pressure difference/resistance OR CO = (MAP-VP)/TPR
- analogous to I = V/R
How do changes in vascular resistance determine distribution of CO among tissues?
- if you change the diameter of a vessel through vasoconstriction or vasodilation, then according to Poiseuille’s Flow, you can drastically affect flow through that vessel
How do vascular resistance, blood viscosity, vessel length, and vessel radius affect blood flow?
Flow = pressure diffpiradius^4/(8viscositylength)
OR
Q = deltaPpir^4/(8nl)
- key point is that radius is ^4
How is the pulsatile flow of blood converted to steady flow in capillaries?
- elastic walls of aorta and arteries dampen pulsatile pressure, so by the time they reach capillaries, more like a continuous flow
- helps because pulsatile needs more work (accelerating mass vs constant vel)
What is vascular compliance?
C = deltaV/deltaP
- represents the elastic properties of vessels (if very compliant, then easily expanded, like veins but not arteries)
- compliance is opposite to elasticity
- determined by elastin fibers vs smooth muscle and collagen in vessel walls
- more compliance = lower pulse pressure (can expand more so doesn’t maintain pressure as well)
What is the relationship between vascular wall tension, transmural pressure, radius, and wall thickness?
Wall tension = transmural pressureradius/wall thickness
OR
T = deltaPtmr/u
- Wall tension is the circular tension that exists around/on the wall of a vessel
What is Fick’s Principle and how can it be used to determine transcapillary efflux?
- Fick’s principle: the amount used is the equal to the amount that enters minus amount that leaves
x_used = xi-xo = Q*([x]i-[x]o)
for myocardial O2 consumption:
mVO2 = CO*([O2]arterial-[O2]venous)
How does the balance between hydrostatic and oncotic pressures in a capillary bed determine direction of transcapillary transport?
- hydrostatic pressure is difference between capillary blood pressure and interstitial pressure and typically results in stuff going out of vessel into interstitium (because pressure there is basically 0) –> filtration
- oncotic pressure is due to osmotic force by proteins; more proteins in blood, so fluid comes into vessel –> reabsorption
Flux = k[(Pc-Pi)-(pic-pii)]
- Arterial side of capillaries, Pc is higher and pic is lower; opposite for venous side
What is transmural pressure?
- Difference in pressure between inside and outside of a vessel (across the wall)
Where does pressure fall the most?
- Arterioles
What is the total blood volume? Where is most of the blood volume found?
- about 5L
- Mostly in venous system
Describe resistance, flow, and pressure in parallel and in series
Parallel:
- 1/Rtot = 1/R1+1/R2+….
- deltaP1 = deltaP2 = …
- total res is lower than individual paths
- changing one res pathway doesn’t affect total res that much
- pressure diff is same across all branches
- flow is proportional to 1/Ri
Series:
- Rtot = R1+R2+….
- Q1=Q2=….
- total res is sum of res (most res in arterioles)
- flow is constant, but pressure diff is different between segments
Difference between laminar and turbulent flow
- Laminar: smooth, efficient, slowest at edge, fastest in center
- Turbulent: irregular; needs more pressure for same avg velocity; occurs with large diameter, high velocity, low viscosity, changes in diameter; creates shearing force that damages endo cells
What is mean arterial pressure?
diastolic pressure + 1/3(systolic press-diastolic press)
OR
1/3systolic press + 2/3diastolic press
- basically like this because more often in diastole than in systole –> changes with heart rate
What is bulk transport?
- cargo from point A to point B in the CV system; can use to measure O2 consumption
rate = flowconc
OR
x=Q[x]
What are the unique properties of cardiac muscle?
- striated
- autonomic (doesn’t need neural input)
- interconnected mono-nuc cells in weaved collagen
- longer repol than skeletal muscle
- ATPase activity slower than skeletal
- **thin-filament regulated (as opposed to thick for smooth muscle)
- mechanical and electrical coupling between cells (desmosomes provide mech coupling, gap junctions for electrical)
- lots of mitochondria
Describe the cross bridge cycle
- resting muscle: low Ca in cell, TN-TM complex inhibits actin-myosin binding; action potential leads to release of Ca from SR to increase Ca in cell; TN binds Ca and moves TM out of the way so actin and myosin can bind
1) ATP binds and hydrolyzes to ADP and Pi to activate myosin; Pi leaves and myosin strongly binds to actin
2) ADP released and myosin head pivots
3) ATP binds to myosin head and detaches
4) reactivate myosin head with hydrolysis of ATP
Describe the length tension (Frank-Starling) relationship in cardiac muscle
- increase in preload –> increase in SV
- length-tension relationship (some optimal length where if you lengthen the sarcomere, get a better overlap, better Ca sensitivity, and inc Ca release and a better contraction –> increased preload stretched the sarcomeres)
Relate myocyte mechanics to ventricular function
- inc in volume –> inc in ventricular circumference –> inc in length of individual myocytes
- T=P*r/u
Identify sarcomeric changes associated with heart failure
- hypertrophy: concentric cell growth; changes mainly in Ca sensitivity
- Dilation: eccentric cell growth; changes in force output
What is cardiac output?
CO = stroke volume*heart rate
What factors control stroke volume?
- Preload: length-tension; higher preload = higher force
- Afterload: pressure that ventricle needs to overcome; usually aortic pressure
- Contractility: force that heart contracts with; norepinephrine regulates
What are the proteins involved in contraction?
- Myosin: 2 heavy and 4 light chains
- Actin: binds tropomyosin and troponin
- Thin filament regulatory proteins:
- TN-C: contains one Ca binding site
- -TN-I: regulated by phosphorylation/PKA sites; actin cannot bind myosin when in the way
- -TN-T: binds tropomyosin
- -Tropomyosin: lays over actin in the myosin binding sites
Describe titin
- giant protein
- functions as an elastic spring
- resting tension of myocyte
- N2B is stiffer and shorter than N2BA
Define cardiac output
- CO is the volume of blood pumped per min by the left ventricle
CO=SV*HR
- usually about 5L/min at rest
What are the four phases of the cardiac cycle and describe changes in pressure and volume in each chamber accordingly
1) Diastole:
- LA filled with oxy blood and mitral valve is open so LV fills with blood passively
- LA contracts and builds atrial pressure
- mitral valve is open and blood starts to fill in LV and also increase pressure in LV
2) Isovolumetric contraction:
- LV contracts as pressure increases really quickly
- volume stays same because mitral valve closed when filled enough and aortic valve not open yet
3) Ejection phase:
- LV contracts and aortic valve opens
- LV starts to relax and ejects blood so pressure starts to decrease and volume decreases
- aortic valve stays open for a little bit due to inertia of blood moving while LV relaxes
4) Isovolumetric relaxation phase:
- aortic and mitral valves closed and LV continues to relax so volume is same, but pressure decreases until so low that mitral valve opens again
Define systolic and diastolic pressure-volume relations and ventricular function curves
End diastolic pressure-volume relationship (EDPVR):
- represents the preload on the heart
- curve representing pressure-volume relation while passive, before contracting (at the end of diastole)
Systolic pressure-volume relationship (SPVR):
- curve representing pressure-volume relation at peak of contraction
- depends on afterload (aortic pressure)
Describe the Frank-Starling Law of the Heart
1) if increase in EDV, then increase in force of contraction
2) healthy heart functions on ascending limb of Starling curve
3) CO must equal venous return; CO from LV and RV must match
- titin is stiff
- as sarcomeres are stretched, more Ca binding sites, so more contraction
- closer lattice spreading
Describe relative changes in pressure and volume through the cardiac cycle (PV Loops)
1) Filling phase:
- ESV is bottom left; lowest pressure and lowest volume right after systole
- LV relaxes and fills with blood passively from LA with little change in pressure
- end volume is end diastolic volume
2) Isovolumetric contraction phase:
- LV contracts, mitral valve closed, but aortic valve alos closed since LV pressure not high enough to over come yet, so volume stays same
3) Ejection phase:
- LV pressure exceeds aortic pressure so aortic valve opens
- blood leaves so volume decreases
- pressure increases because blood cannot leave aorta as fast as it enters
- pressure starts to fall as LV starts to relax
4) Isovolumetric relaxation phase:
- LV pressure below aortic pressure, aortic valve closes, still relaxing so mitral valve still closed
Define stroke volume, ejection fraction, stroke work, and pulse pressure, and to identify them graphically on a PV Loop diagram
Stroke Volume:
- amount of blood pumped per beat
- EDV-ESV = SV
Ejection Fraction:
- fraction of EDV ejected during systole
- SV/EDV = EF
Stroke Work:
- energy per beat
- area of PV loop
Pulse Pressure:
- systolic pressure - diastolic pressure
Define preload, afterload, and contractility, and describe how altering these variables changes ventricular function
Preload:
- EDV; the amount that initially stretches the LV
- *ventricular compliance: dec compliance = more stiff (hypertrophy) = lower EDV at given pressures (shifts EDPVR left)
- if you inc preload, you immediately increase SV (Starling’s law) bc EDV increases but ESV stays same and stroke work inc
- next beats are same SV because ESV is same
Afterload:
- ~aortic pressure
- wall thickness and radius affect
- inc afterload, decrease in SV because less time for ejection (since need to reach higher pressure before aortic valve opens), also less pressure due to dec shortening velocity and lower ejection velocity
- EDV is same, EF dec, ESV inc, SV dec
Contractility:
- strength of contraction indep of preload or afterload
- new Startling curves
- regulated by drugs and NS
- if inc inotropy, shift Starling curve to left (greater systolic pressure at any vol); see inc SV, dec ESV, inc EF
How do HR and SV affect CO?
CO=HR*SV
- HR is highly regulated by autonomic NS
- HR can change more than SV so can influence CO more
- high HR means less time for filling –> lower stroke volume
- SV affected by preload, afterload, and contractility
What is active tension?
- the difference in force between peak sys press and dia press curves
- basically the tension developed purely by contraction, indep of preload
- presented by Starling Curve
Describe the differences between fast and slow cardiac APs graphically
Slow APs:
- Phase 0: rising phase due to Ca channels
- no Phase 1 or 2
- Phase 3: repol due to IKr and IKs (delayed rectifier K channels)
- Phase 4: steady depol from If
Fast:
- Phase 0: rising phase due to Na channels
- Phase 1: IKto gives a partial repol and makes Ca entering more favorable
- Phase 2: plateau phase where L type Ca channels open
- Phase 3: delayed rectifier IKr and IKs channels open to repol
- Phase 4: flat, some inward rectifier
Which cells are fast and slow cardiac APs found in respectively?
Fast:
- atrial muscles
- ventricular muscles
- Purkinje fibers
Slow:
- SA nodal cells
- AV nodal cells
Describe the properties of ion channels that underlie fast and slow cardiac APs
Fast APs:
- Phase 0: rapid depol of entry of Na ions
- Phase 1: partial repol due to inact of Na gates and act of IKto
- Phase 2: plateau where L-type Ca channels are open influx are balance by IKr and IKs
- Phase 3: Ca gates start to inact and act of IKr and IKs
- Phase 4: IKr and IKs deact and IK1 holds Vm near Ek
Slow:
- Phase 0: upstroke due to Ca channels and not as fast as Na
- no phase 1 or phase 2
- Phase 3: IKr and IKs cause repol
- Phase 4: slow depol that brings cell back to threshold automatically due to funny current –> activated by hyperpolarization after IKr and IKs –> brings in Na and out K, but mainly in Na so depols slowly
Describe the ionic mechanisms that account for the ability of pacemaker cells to generate firing without neural input
- repetitive slow APs due to If causing a slow depolarization naturally
Describe the significance of IK1 channels in myocardial cells with fast APs
- maintain resting membrane potential around EK after AP
Describe the significance of If or Ih currents in cells with slow APs
- causes the slow depol that allows cells in SA and AV node to fire automatically
Discuss the mechanism and significance of overdrive suppression
- Overdrive suppression is when AV node cells reach APs with a higher frequency than naturally because of signals from the SA node, which generates APs faster than the AV does naturally
Define the absolute refractory period
- 2nd AP cannot be initiated until most of Na inactivation is removed (during repol phase)
Define the relative refractory period
- threshold is elevated for an AP until after repol phase due to compete removal of Na inactivation and complete deactivation of IKr and IKs)
Describe Na channels
- ## depol causes rapid activation then voltage-dep inactivation
Describe Ca channels
- similar to Na channels
- L type: long; high depol causes rapid activation then voltage-dep and cytoplasmic Ca-dep inactivation; mainly in cardiac muscle
- T type: transient; low depol activated then inactivate
Describe time-dep K channels
IKto:
- transient outward
- depol leads to act and inact slower than Na channel
- Phase 1 of fast APs
IKr and IKs:
- rapid and slow delayed rectifier
- depol leads to activation
- Phase 3 of fast and slow APs
Describe the inward rectified K channels
IK1:
- conduct inward K current when VmEk
- hold cells near Ek between APs
Describe the funny current
- turned off at depol and turned on at hyperpol
- permeable to both Na and K (Erev = -30)
What is HERG?
- anti-target for new drugs
- IKr is a tetramer of HERG and important for repol in both fast and slow APs
- altered HERG can lead to arrhythmias
How do electrical impulse spread from cell to cell
- through gap junctions between cells, there are connexins that let ions pass
Describe the cardiac conduction pathway
starts in SA node in high RA –> RA –> LA (P wave) –> AV node b/w tricuspid and mitral valves b/w atria and ventricles (junction) –> delay before entering ventricles –> bundle of His –> left and right bundle branches –> Purkinje fibers
Compare ventricular AP to an ECG
- Phase 0 = QRS
- Phase 2 = ST segment
- Phase 3 = T wave
- Phase 4 = isoelectric segment
What is T wave and QRS in the same direction but repol and depol not?
- Endocardium depol earlier than epicardium, but repol later than epicardium
- so repol going away from the electrode looks like a positive deflection
Describe the components of the ECD
- P wave = atrial depol
- QRS = ventricular depol
- T wave = ventricular repol
- PR interval = index of conduction time across AV node
- QT interval = total duration of depol and repol
What happens with SA node abnormality?
- slow sinus rate
- taken over by other pacemakers that can be too fast or too slow
Describe the types of AV block
1st degree: conduction delayed but all P waves conduct to ventricles
2nd degree: some P waves conduct
3rd degree: no P waves conduct; ventricular pacemaker takes over
Describe the different bundle branch blocks
Right bundle blocked: wide QRS w/ delayed conduction to right ventricle
Left bundle blocked: wide QRS w/ delayed conduction to left ventricle
Left fascicles blocked: shifts in depol, but no wide QRS
What are the 3 common mechanisms leading to arrhytmia?
1) abnormal reentry pathways:
- unidirectional block and slowed conduction
2) ectopic foci:
- focus of myocardium acquires automaticity and rate is faster than SA node
3) triggered activity:
- afterpolarizations due to preceding AP
Describe the gene defects and molecular basis of long QT syndrome
- mutations in cardiac ion channels
- AD form (Romano-Ward syndrome): 200+ mutations mainly in IKs, IKr, and Na channels
- AR form (Jervell-Lange-Nielson syndrome): mutations in IKs also have deafness
- mutations in K channel subunits (LQT1) –> reduce number of K channels expressed –> reduced size of IKr and IKs current –> weaker repol –> longer plateau
- mutations in Na channels (LQT3) prevent them from inactivating completely –> prolong phase 2 due to more depol
List the cardiac ion channels and the phases of the slow and fast responses that are targeted by the various antiarrhythmic drugs
Ion channel targets:
- Na channels
- Ca channels
- K channels (IKr and IKs)
- beta-adrenergic receptors
- Na channel blockers for LQT3 due to elongated phase 2
- K channel openers for LQT1 or LQT2 but none currently exist
Describe the cellular mechanism of triggered (early and delayed) afterdepolarizations
EAD:
- during late phase 2 and phase 3
- re-activation of Ca channels due to elevated Cai from prolonged phase 2
DAD:
- during early phase 4
- inc Cai –> inc Na/Ca exchange (3 Na in/1 Ca out) –> depol due to Incx
Describe how a re-entrant, or circus, arrhythmia originates
- two requirements:
1) uni-directional conduction block
2) conduction time around the circuit is longer than refractory period
-
Describe the basis of use-dependent block of Na channels by class I antiarrhythmic drugs
- drugs target cells that are over-active with high firing rates or that are abnormally depolarized
- this targets defective cells and prevents affecting normal cells
- hydrophilic drug enters pore when channel is open
Describe how class I antiarrhythmics increase Na channel refractory period, whether or not they prolong phase 2 of the fast response
- drug initially blocks and enter channel during open state, but have a higher affinity during closed state and stabilize that closed/inact state and prolong the time the channel spends in the inact state
- class Ia and Ic drugs block K channels to delay repol and prolong phase 2 –> more Na channels are inact –> longer refractory period
Describe how beta-adrenergic receptor blockers help suppress arrhythmias
- reduce If, ICa, and IKs current –> reduce rate of diastolic depol in pacemaker cells, reduce upstroke rate, and slow repol –> pace rate is reduced and refractory period is prolonged
- AV nodal re-entry terminated
- control ventricular rate during afib
- dec phase 4 slope –> dec rate of firing –> dec automaticity
- prolonged repol of AV node –> inc effective refractory period –> dec re-entry
Describe how class III drugs increase refractory period
- block IKr channels
- leads to prolonged phase 2 and prolonged refractory period
- inc effective refractory period –> dec re-entry
Describe how class IV antiarrhythmic drugs (Ca channel blockers) reduce re-entry via effects on conduction velocity through the AV node and refractory period of the AV node
- block Ca channels –> slows Ca upstroke in slow AP cells –> slows conduction velocity in AV node –> dec re-entry
- prolong refractory period –> dec re-entry
- also, since reduced peak Ca upstroke, you have reduced K repol
Describe how increasing refractory period may help suppress re-entrant arrhythmias
- tissue in refractory period cannot generate an AP so the re-entrant arrhythmia would be extinguished
Describe how some antiarrhythmic drugs can suppress arrhythmias by decreasing cardiac automaticity
- class II beta blockers block If so that rate of depol during diastole is reduced and rate of firing (decreasing cardiac automaticity) is decreased –> slows conduction velocity –> dec re-entry
Describe how adenosine can help suppress cardiac arrhythmias
- through GPCR (similar mechanism to beta blockers), can inc K current, and dec Ca and If currents
- dec If and ICa –> dec diastolic depol and weaker upstroke –> slowed conduction velocity
- adenoside binds to receptor –> activated G protein –> inhibits cAMP –> reduces cAMP –> reduces PKA –> reduces phosphorylation of Ca channels –> closes Ca channels –> smaller Ca current –> smaller upstroke
- G protein binds to IKado –> inc in K current –> faster hyperpol
What happens in long QT syndrome?
- prolongation of the plateau phase 2 of fast AP cells in ventricular myocytes –> ventricular tachycardia (torsades de pointes) –> ventricular fibrillation –> syncope –> sudden cardiac death
What is Brugada syndrome?
- form of congenital arrhythmia
- ventricular fibrillation occurs
- 30+ different mutations in Na channels –> reduce peak inward Na current
What happens in Finnish familial arrhythmia?
- beta-adrenergic receptors upregulate Ca channels, but not K channels
- yotiao normally targets PKA of Ca and K channels by binding to them
- however binding to K channels is impaired –> diminished beta receptor upreg of K channels
- with sympathetic activity, Ca depol, but not enough K repol
What are the two sources of arrhythmias?
1) inappropriate impulse initiation in SA nodes:
- ectopic foci (SA node too slow or ectopic foci too fast)
- EADs (depol during phase 2/3 from Ca)
- DADs (depol during phase 4 from Ca and NCX)
2) disturbed impulse conduction in nodes, conduction (Purkinje) cells, or myocytes:
- conduction block (1, 2, 3 degree)
- re-entry (requires uni-directional conduction block and conduction time around circuit is longer than refractory period)
What is the primary mechanism of class I drugs?
- blocking voltage-gated Na channels (slower upstroke)
- affect fast response cells mainly
- decrease conduction rate and increase refractory period
- block Na channels –> dec phase 0 upstroke velocity –> dec conduction velocity –> dec re-entry
- inc effective refractory period –> dec re-entry
Describe class Ia Na channel blockers
- slowed upstroke (block of Na channels due to class I)
- delayed repol (block of K channels due to class III)
- prolonged refractory period
Describe class Ib Na channel blockers
- slowed upstroke (block of Na channels due to class I)
- prolonged refractory period
- phase 2 NOT prolonged, actually shortened
- purest form of class I (because only Na channel block and not K channel)
Describe class Ic Na channel blockers
- most pronounced slowed upstroked
- prolonged phase 2
- powerful prolongation of refractory period
What are two mechanisms to terminate re-entry?
1) slow AP conduction velocity –> reduce upstroke rate –> more likely to fail to propagate through depressed region –> convert to bi-directional block
2) prolong refractory period –> refractory tissue will not generate an AP
What is the paradox in combating re-entry?
- try to slow conduction velocity, but this means that the signal being propagated is less likely to be shorter than the refractory period, meaning that it will be able to excite tissue since they will no longer be in the refractory period
What is so special about Amiodarone?
- class III antiarrhythmic but has class I activity
- reduces conduction velocity because blocks Na channels
- also dec rate of diastolic depol (phase 4) in pacemaker cells
- dec conduction velocity –> dec re-entry
- dec rate of firing –> dec automaticity
How do you treat paroxysmal supraventricular tachycardia?
acute: adenosine (short half-life)
chronic: AV node blockers (class II, class IV, class II, digoxin), cather ablation of ectopic foci
How do you treat atrial fibrillation?
acute: AV node blockers, electrical cardioversion
chronic: AV node blockers with anticoag (warfarin), cardioversion with maintaining sinus rhythm with drugs (class III, class Ic)
How do you treat ventricular tachycardias/fibrillation?
prevent sudden cardiac death
acute: amiodarone, lidocaine, pocainamide
chronic: beta-blockers, mabye amiodarone
What is the half-life of class II esmolol?
10 min
What is the half-life of class II amiodarone?
13-100 days
What is the half-life of adenosine?
What are class I antiarrhythmic drugs?
block Na channels
What are class II antiarrhythmic drugs?
beta blockers
What are class III antiarrhythmic drugs?
block K channels
What are class IV antiarrhythmic drugs?
block L-type Ca channels
Describe the mechanisms by which PKA-mediated phosphorylation of Phospholamban, L-type Ca channels, RyRs, and troponin I affect inotropy and lusitropy
Phospholamban:
- PB inhibits SERCA
- when phos, PB dissociates from SERCA, so SERCA reuptakes more Ca into SR
- inc lusitropy (better relaxing)
- inc inotropy by inc SR Ca load
L-type Ca channels:
- phos of these channels slows inactivation so more CICR and inc inotropy
RyRs:
- when phos, more sensitive to Ca (less Ca for same Ca release)
- inc inotropy
Troponin:
- normally, TnI inhibits interaction between actin and myosin
- when phos, decrease sensitivity of Ca –> faster dissoc of Ca –> inc lusitropy –> heart fills more quickly
Describe how HCN, L-type Ca, RyRs, and GIRK channels contribute to autonomic control of heart rate
HCNs (hyperpolarization-activated cyclic nucleotide-gated channels):
- symp stim: inc cAMP –> cAMP bind directly to HCN channels to make them more likely to open –> more If to inc rate of diastolic depol –> inc heart rate
- para inh: dec cAMP –> HCN less likely to open –> less If to dec diastolic depol –> dec heart rate
L-type Ca:
- symp stim: cAMP activates PKA –> phos L-type Ca channel –> slows inactivation –> inc Ca current –> inc heart rate
- para inh: dec cAMP –> PKA less activated –> less phos of LTCCs –> no slowing of inact –> dec/normal Ca current –> dec heart rate
RyRs/NCX:
- symp stim: inc SR Ca load when PKA phos PB, RyRs, and LTCCs –> more Ca release –> diastolic depol with more inward current from NCX –> inc heart rate
- para inh: less Ca release –> less diastolic depol with less inward current from NCX –> dec heart rate
GIRK (G-protein couple inwardly-rectifying K):
- para inh: beta/gamma Gsubunit binds to GIRK –> activated IKACh –> keep Vm near EK –> slow firing freq –> dec heart rate
Describe the differences between vascular smooth muscle cells and cardiac myocytes
VSMCs:
- small
- mononucleate
- have gap junctions
- smooth because myofilaments not in sarcomeres
- not troponin or tropomyosin
- don’t need Ca release from SR for VSMCs
- slower rate of contraction but more sustained
- thick filament regulation
- both have SERCA and PLB
Describe the molecular steps involved in Ca regulation of vascular smooth muscle contraction
- doesn’t need AP; can be done by stretching via myogenic response
- Ca enters from SR or Ca channels –> Ca binds to calmodulin –> Ca-CaM binds to myosin light chain kinase and activates it –> MLCK phos/activates myosin head –> cross bridge
- cAMP activates PKA which phos myosin to INHIBIT its activity –> relaxation
Describe the mechanism by which sympathetic stimulation (via alpha1 adrenergic receptors) alters vascular tone
- symp stim –> vasoconstriction
- alpha1 receptors are GPCRs (Gq) that activate PLC –> activate IP3 –> release Ca from SR –> contraction
- also activate PKC that phos LTCCs –> activates more Ca release (CICR)
Describe the arterial baroreceptor reflex arc
- baroreceptors are pressure-sensitive neurons in aortic arch and carotid sinus
- respond to stretch (high BP) by increasing firing rate conferred by Na channels that are mechanosensitive (stretch causes Na channels to open and send APs)
- neurons project to brainstem which then output symp and para fibers to the heart and symp fibers to vasculature
- if inc fire rate –> dec symp and inc para output
Name four tissue metabolites and the mechanisms by which they control local flow to a capillary bed
1) decreased PO2
- chemoreceptors in aortic/carotid bodies
- low PO2 –> inc symp output
2) increased PCO2/decreased pH
- same as above
- high PCO2 –> inc symp output
3) increased K
- K leaves cell in active skeletal muscle
- Na/K pump can’t keep up so K accumulates in interstitial space
4) increased adenosine
- produced by hydrolysis of ATP
- adenosine binds to A2 purinergic receptors –> GPCRs (Gs) –> inc cAMP –> vasodilation by PKA inhibiting MLCK
Describe the myogenic response
- feedback mechanism to maintain constant flow when you have changes in pressure (when too low, inc; when too high, dec)
- stretch –> VSMC contraction by opening stretch-activated Trp channels –> Ca comes in and causes vasoconstriction
Describe how NO and endothelin regulate vascular smooth muscle tone
NO:
- NO is a potent vasodilator
- ACh activates GPCRs on endothelial membrane –> ER releases Ca and binds to CaM –> activates NOS –> makes NO –> diffuses to smooth muscle cell and activates guanylate cyclase –> produces cGMP –> activates PKG –> PKG activates SERCA and inhibits LTCCs–> dec Ca –> dec contraction –> vasodilation via dec MLCK activity
Endothelin:
- potent vasoconstrictor
- endothelin from endothelium binds to ET receptors (GPCRs on VSMCs) –> Gq so inc Ca –> vasoconstriction
Describe the renin-angiotensin-aldosterone system and how it regulates BP
- long term BP control
- renin released into circulation by kidney when symp stim, dec BP in renal artery, or dec Na reabsorption in kidney
- renin cleaves angiotensinogen to angiotensin I –> cleaved by ACE to angiotensin II –> potent vasoconstrictor via bindings to GPCRs on VSMCs
- angiotensin II also stim symp, stim aldosterone release from adrenal cortex (promotes reabsorption of Na and H2O), stim release of endothelin, and stim release of ADH from pituitary (inc H2O reabsorption and vasoconstricts)
Describe the origin and effects of atrial natriuretic peptide on BP
- ANP is a peptide release by atria that vasodilates
- excretes sodium
- secretion stimulatied by mechanical stretch of atria
- ANP acts on natriuretic peptide receptors (guanylate cyclases) that produce cGMP –> actvate SERCA –> dec Ca –> dec vasoconstriction
- ANP inc glomerular filtration rate and inc secretion of Na and H2O
- ANP vasodilates (longer lasting than NO)
- ANP inhibits release of aldosterone and renin
Describe how G protein coupled receptors work
- ligand binding –> intracellular signaling
- agonist binds receptor, GTP replaces GDP on alpha subunit, dissociate alpha and beta/gamma subunits, each can be signals
- deactivated when GTP dephos to GDP, alpha combines with beta and gamma
Describe Gs, Gi, and Gq GPCRs
- Gs: stimulatory for cAMP production by adenylate cyclase
- Gi: inhibitory for cAMP production by adenylate cyclase
- Gq: activation inc intracellular Ca via phospholipase C and PKC
Describe parasympathetic regulation of inotropy
There is very little parasympathetic control/innervation of ventricles
Map the sequence of major events between the initiation of an action potential in a cardiac muscle fiber, through contraction
- AP spreads into T-system
- Ca channel in T-membrane opens an allows entry of extracellular Ca
- this triggers the opening of RyR2 in the SR membrane
- Ca ions leave SR lumen and enter myoplasm and bind troponin
- actin-myosin cross-bridge cycling and contraction occurs
Describe the processes that control relaxation of contraction by removing Ca from the myoplasm
1) SERCA2 pumps:
- in longitudinal SR
- 2 Ca per cycle
- SR surrounds myofibrils, so SERCA is dominant
- Vm = 0 so requires less energy to transport Ca across
2) NCX:
- in junctional domains of plasma membrane and T-tubules
- 3 Na in/1 Ca out
3) PMCA
- extrudes Ca and uses ATP
Compare and contrast EC coupling in skeletal and cardiac muscle
- both are elicited by an increase in myoplasmic Ca conc –> binding Ca to troponin allows actin-myosin interaction
- both have SR as chief source of Ca that causes contraction
- both have release of Ca originating between terminal cisternae of SR and plasma membrane/T-tubule
- cardiac REQUIRES external Ca
- skeletal DOES NOT REQUIRE external Ca
- cardiac is Cav1.2 and RyR2
- skeletal is Cav1.1 and RyR1
Describe how the exchange of 1 Ca for 3 Na ions, together with membrane potential and the Na and Ca gradients, governs the direction of Na and Ca movements via NCX
- the Vr where transport reverse directions is figured out by:
Vr=3ENa-2ECa
- the Nernst potential gets bigger if the outside conc is bigger
- at rest, Vr = -74mV –> Ca leaves until Cai = 100nm
- but if Nai were to increase (maybe from Na/K pump blocker) (decreased ENa and making Vr even more negative) then Cai increases to maintain Vr
- during depol, Ca enters cell and Na exits
- during repol, Cai increases due to SR release and you switch direction and Ca exits while Na enters
Explain why the extrusion of Ca from the cytoplasm via NCX can cause membrane depolarization
- if Cai were to suddenly increase (like it does in SA nodal cells in an oscillatory manner being released from the SR) then the NCX would pump out Ca and bring Na in, so there would be an inward current; this inward current causes the cell to depol
Identify basic elements of calcium homeostasis in the myocardium
- NCX
- LTCC inactivation through Ca-dep inactivation (CDI)
- CDI depends on Ca through LTCCs and through RyR2
- if Ca via RyR2 in SR inc, then CDI inc and less Ca through LTCC
- if Ca via RyR2 in SR dec, then CDI dec and more Ca through LTCC
Explain how stimulation of beta-adrenergic receptors increase both contraction strength, and rate of relaxation, of cardiac muscle
- beta adrenergic GPCR stimulated –> produce cAMP –> activates PKA –>
1) phosphorylates LTCC to increase Ca current –> increases trigger of RyR2 –> inc Ca released and –> inc inotropy/more contraction
2) phosphorylates RyR2 so that it is more sensitive to trigger Ca –> more CICR for less trigger –> inc inotropy and more contraction
3) phosphorylates PLB to prevent inhibition of SERCA so more Ca reuptake into SR –> inc lusitropy and more Ca load in SR so inc inotropy
4) phosphorylates troponin to make less sensitive to Ca which speeds rate of Ca dissociation –> inc lusitropy
Describe why Timothy syndrome mutations of the LTCC could result in a lengthened cardiac AP and why Brugada syndrome mutations of the LTCC could result in shortened APs
Timothy Syndrome:
- de novo mutations in Cav1.2 (LTCCs)
- supresses voltage-dep inactivation
- AV block and long QT intervals due to prolonged ventricular AP (Ca channel stays open longer since inactivation is suppressed)
Brugada:
- mutations of Na channel, IKto channel, Ca channel, LTCC, etc.
- large reduction in magnitude of LTCC current
- short QT interval –> weaker LTCC –> shorter AP
Identify the mechanism whereby CPVT mutations, in combination with activation of beta adrenergic receptors, causes ectopic depolarizations
CPVT (catecholaminergic polymorphic ventricular tachycardia):
- ECG abnormalities with exercise or catecholamines
- mutations in RyR2 –> leak of Ca out of SR/make RyR2 more sensitive to activation by Ca
- beta adrenergic receptors increase SR Ca content + CPVT mutation –> release of Ca that is not triggered by LTCC during phase 2 of AP but instead after repol –> this Ca is extruded by NCX –> Na comes in and depolarizes cell –> ectopic APs –> arrhythmias
What is the hallmark of systolic heart failure?
- HFrEF
- LVSD
- ventricular enlargement –> dilated cardiomyopathy
What are causes of systolic heart failure?
- destruction of heart muscle cells (MI)
- overstressed heart muscle (tachycardia)
- volume overloaded heart muscle (mitral regurg, high CO)
What change in the PV loop do you see in systolic heart failure?
- starling curve shifts down (lose inotropy)
- dec SV due to inc ESV
- lower systolic BP
What is the hallmark of diastolic heart failure?
- HFpEF
- ventricular wall thickening: LVH or HCM
What are the causes of diastolic heart failure?
- high afterload (HT, aortic stenosis)
- myocardial thickening/fibrosis (HCM)
- external compression (pericardial effusion)
What does the PV loop look like in diastolic heart failure?
- EDV curve shifts up (for a given preload/EDV, more pressure needed because heart is stiffer)
- decreased SV because EDV is decreased
What are the effects of right heart failure?
- dec circulating blood flow (forward RV HF)
- inc venous pressure (backward RB HF)
What are the causes of right heart failure?
- left heart failure (backward HF form LV leads to back up into lungs and RH has to work harder to push against that)
- lung disease (cor pulmonale)
- RV volume overload (tricuspid regurg)
- damage to RV myocardium
Describe how the sympathetic and parasympathetic divisions of the autonomic nervous system function to maintain a stable internal environment within a narrow physiological range
- two-neuron system: pregang neuron from CNS to autonomic ganglia containing postgang neuron to target
Sympathetic:
- pregang neurons from thoracic and lumbar spine to innervate postgang axons using ACh
- postgang neurons release NE and are in ganglia of sympathetic trunk and travel to sweat glands, blood vessels, hair follicles, etc.
- symp controls vasodilation and vasoconstriction and also increases HR and force of contraction
Parasympathetic:
- pregang from brainstem and sacral spine
- cranial nerves (3, 7, 9, 10)
- ACh as neurotransmitters
- innervate colon, rectum, bladder, genital organs
- decrease HR and force of contraction
Describe how the ANS maintains homeostasis to the control of blood pressure
- symp stim: increase BP through inc in HR and contractile force and vasoconstriction
- para stim: decrease BP through dec in HR and contractile force
Describe the role of the hypothalamus in regulating the CV system via the ANS and posterior pituitary
- hypothalamus considered head ganglion of ANS because it integrates info from several regions to the pregang neurons in CNS
- hypothalamus controls release of hormones via pituitary
- low BP detected –> release of vasopressin in post pituitary –> vasoconstriction –> kidneys increase H2O retention
Describe the actions of sympathomimetic and parasympathomimetic drugs on heart function
- mimic sympathetic and parasympathetic activity
How does the adrenal medulla play a role in sympathetic nervous system?
- neuroendocrine gland
- postgang neurons in adrenal medulla secrete epinephrine and NE which bind to adrenergic receptors in blood stream
Describe the different receptor subtypes for ACh
- nicotinic: present in cell body of postgang neurons
- ligand-gated, non-selective cation channel
- ACh binds and channel opens allowing Na and K to cross membrane –> depol and excitation
- muscarinic: present on effector cells of cardiac and smooth muscle and glands
- linked to G protein
- ACh binds –> G protein activated –> G protein activates or inhibits other stuff
- in atrium, ACh from vagus nerve binds and activates G protein then opens K channels –> hyperpol and slowing down of heart
Describe the different receptor subtypes for NE
- alpha and beta receptors
- NE only activates alpha1, alpha2, and beta1
- epinephrine activates those 3 and beta2
Describe the mechanism of NE sympathetic on an SA node cell
NE binds to beta1 receptor –> G protein activated –> activates adenylate cyclase –> produces cAMP –> opens Ca channel and HCN –> influx of Ca and If
- higher amplitude
- faster upstroke
- inc rate
- inc force
- inc rate of depol during diastole
Describe the effect of ACh on an SA node cell
ACh binds to M2 receptor –> activates G protein –> dec activity of adenylate cyclase –> decrease production of cAMP –> close Ca channels and open K channels to allow for repol
- dec rate
- dec force
- dec amplitude
- slower upstroke
- dec rate of depol during diastole
Describe the baroreceptor reflex parasympathetic and sympathetic activity
Parasympathetic:
- inc BP –> inc stretch –> vagus nerve transmits signal to NTS in medulla –> activates glutamatergic neurons –> inc glutamate –> release ACh on ganglia through pregang neuron –> postgang neuron release ACh onto SA node cells –> dec HR
Sympathetic:
- vagus nerve –> activates glutamatergic neurons –> release GABA –> GABA inhibits release of glutamate in thoracic spine –> decreased release of aCh from pregang to postgang –> postgang decreased release of NE onto SA nodal cells
Recognize the major symptoms associated with heart failure, particularly those related to decreased CO, increased pulmonary venous pressure, and increased central venous pressure
dec CO:
- dec muscle perfusion (fatigue)
- decreased gut perfusion (anorexia)
- decreased kidney perfusion (dec urine; renal dysfunction)
- exercise intolerance (can’t inc CO to meet stress)
inc pulm venous pressure:
- dyspnea (on exertion)
- orthopnea (SOB when flat since more blood back in circulation)
- pulm edema
inc central venous pressure:
- edema
Be acquainted with the functional classification schemes for heart failure
Asymptomatic –> Symptomatic w/ moderate exertion –> Symptomatic w/ minimal exertion –> Symptomatic at rest
Identify the common precipitants of worsening heart failure symptoms, and the variable clinical course of heart failure
inc circulating volume (preload):
- Na in diet
- renal failure
inc pressure (afterload)
- HT
- aortic stenosis
- PE
dec inotropy
- myocardial ischemia
- beta blocker or Ca channel blocker
arrhythmia
- bradycardia
- afib
inc metabolic demands
- fever, infection, etc.
not taking HF meds
Identify the key physical signs of heart failure, and how they relate to the underlying pathophysiology
Low flow
- cool extremities due to peripheral vasoconstriction
- tachycardia to compensate for low SV
- low pulse pressure (can’t create a large systolic output so not a big difference between diastolic and systolic)
Left-sided filling (pulmonary venous pressure)
- rales
- tachypnea
Right-sided filling (systemic venous pressure)
- edema
- hepatosplenomegaly
- JVD a and v waves
Gallops
- S1: mitral/tricuspid close
- S2: aotic/pulmonary close
- S3: rapid expansion of ventricle walls in early diastole –> indicates HFrEF
- S4: atria contracting forcefully to overcome stiff LV
Describe the primary laboratory tests and imaging studies that are most helpful in making a diagnosis of heart failure, including natriuretic peptides, cardiac imaging studies (how to assess LVEF), and hemodynamics obtained from a pulmonary artery catheter
- chest x-ray (large heart in HFrEF, pulm edema)
- natriuretic peptides (BNP secreted in response to ventricular stretch)
- ecg (not directly HF but other findings)
- cardiac imaging (measure EF)
- echo
- right heart catheter (can measure post capillary wedge pressure = left atrial pressure)
Discuss the major significance of heart failure in the US
- common, chronic health care problem that affects survival, quality of life, and health care costs
- median age of patients with HF is 75
Recognize the physiology explains the pathophysiology
uh ok
- function determines dysfunction
-
Define the syndrome of heart failure, and recognize that both a decrease in cardiac output and increase in filling pressures are fundamental to the pathophysiology
- heart failure is defined as the inability of the heart to pump blood forward at a sufficient rate to meet metabolic demands of the body (FORWARD FAILURE)
- dec CO
OR
the ability to do so only if the cardiac filling pressures are abnormally high (BACKWARD FAILURE)
- inc filling pressure/congestion (usually a response to dec CO)
Describe the difference between systolic and diastolic dysfunction
Systolic HF:
- problem with contraction (dec inotropy)
- HFrEF
- LVSD
- DCM
- caused by destruction of heart cells (MI), overstressed heart muscle (tachycardia), or volume overload (mitral regurg, high CO)
Diastolic HF:
- problem with filling (dec lusitropy)
- HFpEF
- LVH
- HCM
- caused by high afterload (HT), myocardial thickening (HCM), external compression (pericardial effusion)
Describe compensatory responses to decreased cardiac output seen in heart failure, including neurohormonal activation of adrenergic and RAAS systems, Frank-Starling increases in preload, and ventricular remodeling via hypertrophy and dilation
Activation of adrenergic system:
- vasoconstriction
- tachycardia
- inc inotropy
- dec CO –> baroreceptor reflex –> adrenergic activation –> inc HR + vasoconstrict
Activation of RAAS:
- vasoconstriction
- salt/H2O retention –> inc volume –> inc LV filling/preload
Frank-Starling inc in preload:
- F-S curve shifts down so to compensate, increase EDV to inc SV
Ventricular remodeling
- ??
Recognize the major goals of therapy, including correction of any reversible causes, reduction of congestion, and optimization of cardiac function
Correct underlying cause of HF
- revascularize if ischemia
- many irreversible though
Eliminate precipitating factors
- infection, anemia
Reduce congestion
- fluid optimization
Improve flow
- med devices
Modulate neurohormonal activation
- positive remodeling
Name the major classes of medications for heart failure, including diuretics, vasodilators, neurohormonal antagonists, and inotropes
Diuretics
- reverse Na and fluid retention (pee off excess fluid)
- really common in HF
- IV inpatient because of poor bioavailability
- right side of F-S curve so that big dec in EDV lead to small changes in SV so you can reduce congestion without affecting CO
Vasodilators
- arterial vasodilation/antihypertensives (dec afterload)
- venous vasodilation (dec preload)
- pulmonary artery vasodilation (dec RV afterload)
Neurohormonal antagonists
1) ACE inhibitors (-pril)
- block AT1–>AT2
- vasodilation
- dec aldosterone activation (dec Na/H2O retention)
- side effects: hypotension, dec renal function, hyperkalemia, cough
2) AT2 receptor blockers (-sartan)
- similar effect to ACE inhibitors
- side effects: no cough like with ACE inhibitors, but similar
3) Aldosterone receptor blockers
- block effect of aldosterone on kidney –> dec Na/H2O retention
- side effect: hyperkalemia
4) Beta-blockers (-olols)
- block beta1 –> dec chronotropy and inotropy
- block alpha 1 –> vasodilate
- side effects: short term loss for long term gain (fluid retention, hypotension, dec CO)
Inotropes
- digoxin (K/Na exchanger), dobutamine (beta agonist)
- short term to reverse shock
- long term HF is worsened though
Describe non-pharmacologic therapies for heart failure, including electrical therapies and advanced therapies
ICD
- LVEF inc SV and dec regurgitation
- usually with ICD
Cardiac transplant
Mechanical circulatory support
Hospice
Describe the non-linear clinical course of heart failure, and how different therapeutic approaches are used at different stages of the disease process
Acute:
- IV diuretics
- IV vasodilators
- IV inotropes for shock
- CPAP for hypoxia (can reduce preload)
- cut back on beta-blockers in severe cases
??
Recognize that most specific heart failure therapies are indicated for patients with HFrEF; for the approximately 50% of patients with heart failure and relatively normal ejection fraction HFnEF, treatment consists of diuretics and management of underlying causes
Improve symptoms:
- diuretics
- inotropes
Prolong survival
- ACE inhibitors
- AT2 receptor blockers
- beta blockers
- aldosterone antagonists
- vasodilators
- CRT
- ICD
Recognize the importance of prevention and list specific prevention goals
- BP
What is the mechanism of action, metabolism, side effects, drug-drug interactions, and monitoring parameters of ACE inhibitors/ARBs?
Mechanism of action:
- ACE inhibitors block ACE and Kinase II which convert AT1 to AT2 and Bradykinin to Inactive Fragments respectively
- bradykinin potent vasodilator and block of AT2/aldosterone production means dec vasoconstriction
- ARBs block AT2 receptor so don’t affect kinase II
Drug-drug interactions (for ACE inhibitors):
- Lithium
- NSAIDs
- diuretics
Side effect:
- bad cough, hyperkalemia, angioedema,
- ARBs don’t have cough but similar side effects
Monitoring:
- Chemistry-7, CBC, BP every month
- for ARB, watch for overproducers of uric acid
What is the mechanism of action, metabolism, side effects, drug-drug interactions, and monitoring parameters of neprilysin inhibitors?
- valsartan+neprilysin blocks AT2 receptor and blocks neprilysin breakdown of BNP
- BNP made during HF
- BNP causes vasodilation, dec fibrosis, dec BP, diureses
- used in placed of an ACE inhibitor
What is the mechanism of action, metabolism, side effects, drug-drug interactions, and monitoring parameters of ivabradine?
- affects chronotropy but not inotropy
- closes HCN channel and delays If –> dec HR
- bad for pregnant women
- monitor for afib
- can affect QT interval
What is the mechanism of action, metabolism, side effects, drug-drug interactions, and monitoring parameters of beta blockers?
Mechanism:
- NE produced by nerve
- NE activates beta1 a lot (and beta2) –> GPCR –> inc cAMP –> inc PKA –> phos of a lot of stuff –> inc inotropy
- beta-blockers are antagonists for these receptors
- need to start low and up-titrate (gets worse before getting better)
- initially dec CO and dec HR –> inc over time
- shields from NE and have upreg of beta1
- 1st gen: propanolol - non-selective and block beta1 and beta2 (dec HR and inotropy)
- 2nd gen: metroprolol - selective for beta1 and beta2 receptors (dec HR and inotropy)
- 3rd gen: carvedilol - antagonist foe beta1, beta2, and alpha1 (vasodilatory)
Describe the mechanism of action, metabolism, side effects/toxicity, drug-drug interactions, monitoring parameters for digoxin
- inc Ca intracellularly
- binds Na/K pump –> Na accumulates in cell –> Na exchanged for Ca with NCX –> inc inotropy and chronotropy
- renally excreted; so contraindicated in patients with renal dysfunction
- toxicities: heart block, vomiting, headache, fatigue, arrhythmia, hypokalemia,
- drug-drug: antiarrhythmics, azole antifungals, verapamil/diltiezam, macrolides, quinine
Describe the mechanism of action, metabolism, side effects/toxicity, drug-drug interactions, monitoring parameters for dobutamine
- beta1 agonist –> inc inotropy
- ADHF short term management
- side effects: angina, tachyarrhythmia
- recommended if hypotensive
Describe the mechanism of action, metabolism, side effects/toxicity, drug-drug interactions, monitoring parameters for milrinone
- inhibits breakdown of cAMP via phosphodiesterases
- ADHF short term management
- recommended if receiving a beta blocker
- side effects: hypotension, tachycardia, arrhythmia, fever
Describe the mechanism of action, metabolism, side effects/toxicity, drug-drug interactions, monitoring parameters for dopamine
- endogenous precursor of NE –> directly stimulate adrenergric receptors
Describe the presenting symptoms and signs of, diagnostic approaches to and treatment for acute pericarditis
Presentation:
- caused by virus, CT or AI disease, uremia, metastatic tumors
- presents with sudden onset of severe chest pain that varies with position
Diagnosis:
- chest pain that varies with position
- pericardial rub on cardiac exam
- diffuse ST elev
- pericardial fluid
- diagnosis of exclusion (presume MI, treat with angiplasty, if not better then consider pericarditis)
- responds to NSAIDs
Treatment:
- ibuprofen 300-800mg po ever6-8hrs
Describe the clinical manifestations, diagnosis and treatment of constrictive pericarditis
Presentation:
- scarring and loss of elasticity of pericardium
- constrains how much can expand during diastole but normal systole–> inc diastolic pressure –> right sided HF
- idiopathic, after cardiac surgery, radiation, infection
- inc JVP, tachycardia, hepatomegaly, edema, ascites
- resembles restrictive cardiomyopathy
- takes long time to develop
- lungs not congested because impaired filling of RV
- often mistaken for liver disease because prolonged high venous pressure causes hepatomegaly and ascites
- dip and plateau during diastole and equalization of diastolic pressures between RV and LV
Diagnosis:
- echo or xray for thickened or calcified pericardium
Treatment:
- surgical stripping of pericardium
Outline the clinical manifestations, diagnosis and treatment of pericardial effusion
Presentation:
- causes: viral or acute idiopathic, metastatic malignancy, uremia, AI disease, hypothyroidism
Diagnosis:
- xray or echo
- look for an enlarged heart and non-congested lung fields (bc RV filling is impaired so lungs are not congested)
- inspiration –> inc filling of RV but dec LV –> dec SV
- ECG shows electrical alternans
Treatment:
- can drain if large effusions with high intrapericardial pressures
- small effusions may be asymptomatic and may not need drainage
Outline the clinical manifestations, diagnosis and treatment of cardiac tamponade
Presentation:
- caused by large pericardial effusion
- presents with same signs as pericardial effusion
- dec RV diastolic filling during inspiration
- distended neck veins
- inspiratory dec in arterial pressure
Diagnosis:
- ECG shows low voltage with sinus tachycardia and electrical alternans with sinus tachycardia
- echo shows collapse of RA and RV in end-diastole and dilation of IVC
Treatment:
- pericardiocentesis
Describe the EKG changes produced by ventricular hypertrophy
- more muscle mass = greater amplitude
- LV hypertrophy –> big R waves in leads I, aVL, V5, and V6
- RV hypertrophy –> big R waves in V1 and V2
Describe the EKG changes produced by myocardial ischemia
- with sudden high O2 demand –> ST depression
- acute clot in coronary artery –> T wave inversion
- transmural injury –> ST elevation
Describe the EKG changes produced by myocardiac injury or infarction
- four stages of evolving transmural MI
1) Peaked T wave (usually only a few minutes and rarely actually see)
2) T-wave inversion
3) ST elevation
4) Q-waves, ST elev, T inversion
Describe the EKG changes produced by electrolyte disorders
Hypercalcemia
- shortened QT
Hypocalcemia
- prolonged QT
Hypokalemia
- due to vomiting, diarrhea, or diuretics
- prolonged QT
- U waves
- inverted T waves
Hyperkalemia
- mild: T wave elevated
- high: P flat, wide QRS and T, wider S
- higher: no P or R, sinusoid
Describe the important parts of a normal EKG
- P wave = atrial depol
- QRS = ventricular depol (normal: .06-.1sec)
- T wave = ventricular repol
- PR interval = time for depol to travel from atria to ventricle (normal: .12-.2sec)
- QT interval: total duration of depol and repol
- depol moving towards positive electrode –> positive deflection (QRS up in left and lateral leads, down in right side leads)
- 12 leads: limb leads I, II, III, augmented limb leads aVL, aVR, aVF, precordial leads V1-V6
- thin lines are .04sec apart
- thick lines are .2sec apart
How do you find the HR on an ECG?
HR = 300/#of heavy lines between two waveform = 1500/#of small lines between 2 waveforms
What difference in ECGs do transmural infarcts show vs. subendocardial infarcts?
- transmural: ST elevation with Q waves
- subendocardial St depression with no Q waves
What are the causes, EKG findings, and treatments for sinus tachycardia?
Causes:
- exercise
- emotion
- hypotension
EKG findings:
- normal waves with increased frequency
Treatment:
- none
- beta blockers
What are the causes, EKG findings, and treatments for sinus bradycardia?
Causes:
- athletes
- may produce fatigue or syncope
- sick sinus syndrome
EKG findings:
- normal waves with decreased frequency
Treatment:
- none
- atropine or pacemaker
What are the causes, EKG findings, and treatments for AV block?
Causes:
- 1st deg: drugs (beta blockers, Ca blockers, digitalis), conduction system disease
- 2nd deg: conduction disease, high vagal/para tone, excess effect of drugs
- 3rd deg: AV node/junctional failure, disruption during surgery
EKG findings:
- 1st deg: PR >.2 sec
- 2nd deg: Mobitz 1 - PR lengthens until P doesn’t conduct, Mobitz 2 - no change in PR, just some P waves don’t conduct
- 3rd deg: P waves and QRS waves are at different rhythms (P faster than QRS)
Treatment:
- 3rd deg: acute - temporary pacemaker, chronic - permanent
What are the causes, EKG findings, and treatments for atrial flutter?
Causes:
- clot may form in left atrium –> embolic stroke
EKG findings:
- P waves 240-320bpm
- multiple P waves per QRS
Treatment:
- treat with anticoag (warfarin), rate control (beta blockers), cardioversion, ablation
What are the causes, EKG findings, and treatments for atrial tachycardia?
Causes:
- usually due to reentry
EKG findings:
- rapid HR (~180bpm)
- narrow QRS
- P waves present but abnormal
Treatment:
- adenosine
- ablate reentry pathway
What are the causes, EKG findings, and treatments for junctional rhythm?
Causes:
- rhythms originate from area surrounding the AV node (the junction)
EKG findings:
- narrow QRS
- no P wave because buried within QRS
- if P wave, then inverted
Treatment:
- none
What are the causes, EKG findings, and treatments for premature contractions?
Causes:
- common as single beat palpitations
EKG findings:
- APC: abnormal P wave preceding, narrow QRS
- VPC: no P wave, wide QRS
Treatment:
- if a lot, then beta blockers
What are the causes, EKG findings, and treatments for ventricular tachycardia?
Causes:
- can lead to death
EKG findings:
- wide abnormal QRS
Treatment:
- amiodarone
- lidocaine
- cardioversion
What are the causes, EKG findings, and treatments for ventricular fibrillation?
Causes:
- requires emergency defib
EKG findings:
- varying, wide QRS
- squiggly lines
- loss of PQRST waveform
Treatment:
- emergency defib
- ICD and meds
What is the algorithm for identifying common cardiac rhythms?
1) is there a P followed by a QRS?
2) is AV block present?
3) are occasional early QRS present?
4) are fast abnormal P waves present?
5) are no P waves present but QRS present?
6) are no P waves and no QRS present?
What are the causes, EKG findings, and treatments for atrial fibrillation?
Causes:
- aging, post-op, heart disease, hyperthyroidism, *dilation or fibrosis of atria
- rapid HR
- loss of atrial kick (lose 20% of filling)
- atrial thrombi
EKG findings:
- irregularly irregular
- no P waves
- irregular QRS waves
- chaotic atrial
Treatment:
- anticoag
- beta blockers, Ca channel blockers
- cardioversion
- ablation
Treatment for bradyarrhythmias
- find/treat reversible causes (ischemia/infarction, hypothyroidism, etc.)
- stop offending meds (beta blockers, Ca channel blockers, antiarrhythmic drugs)
- acute stabilization: beta agonist, pacing,
- long term pacemaker
What is MAT?
Multifocal atrial tachycardia
- 3+ P wave morphologies
What are the irregular supraventricular tachyarrhythmias and how do you generally treat them?
- Afib
- MAT
- Aflutter
- if unstable –> shock
- treat with rate control, antiarrhythmics, or cardioversion
How do you treat Afib?
5 Cs:
- reverse Cause (hyperthyroidism, alcohol, mitral valve disease, infection, PE)
- Control rate
- antiCoagulate
- Control rhythm (cardioversion)
- Cure with ablation but less likely than aflutter
What are the regular supraventricular tachyarrhythmias and how do you generally treat them?
- Sinus tach
- AVNRT
- AVRT
- AFL
- AT
- JT
- treat with adenosine
- then vagal maneuvers, meds only w/ symptoms, betablockers, Ca blockers
- catheter ablation –> 90% cure
How do you treat ventricular tachycardia?
Stable:
- amiodarone
- lidocaine
- procainamide
- treat underlying causes
Unstable:
- SHOCK
- treat underlying causes
- meds
With structural heart disease:
- treat underlying causes
Without structural heart disease
- rarely defib
How can adenosine be used to diagnose regular SVTs?
add adenosine
- if ST –> complete heart block, sinus Ps, ST
- if AVNRT –> terminate
- if AVRT –> terminate
- if AFL –> CHB, flutter waves, AFL
- if AT –> CHB, ectopic Ps, AT or terminate
- if JT –> nothing or terminate
Describe the site and mechanism of action at the nephron, role in the treatment of heart failure, adverse effects - especially as it relates to effects on plasma electrolytes, and loop (high ceiling) of furosemide
Mechanism at nephron:
- normally, ascending limb reabsorbs Na/K/2Cl into ascending limb but no H2O
- furosemide blocks this transporter, so Na leaves in urine
- inc in Mg and Ca excretion
- inc renal flow through RAAS
Role in treating HF:
- used with treating volume overload
- treats acute pulm edema and hypercalcemia
- HF patients have reduced diuretic response because decreased RBF
Adverse effects:
- hypokalemic metabolic acidosis (asecrete K)
- ototoxicity
- hyperuricemia/hyperglycemia
- hypomagnesemia
- overdose –> rapid BP drop –> dizziness, orthostatic hypotension
High ceiling:
Describe the site and mechanism of action at the nephron, role in the treatment of heart failure, adverse effects - especially as it relates to effects on plasma electrolytes, and loop (high ceiling) of thiazides
Mechanism at nephron:
- normally, NaCl reabs occurs via Na/Cl transporter
- thiazides inhibit the Na/Cl cotransporter –> inc excretion of NaCl
- also a Na/Ca transporter on basolateral side that pumps out Na and brings in Ca –> inc reabs of Ca with dec intracellularNa
Role in treating HF:
- supplements effect of furosemide
- helps mild hypertension
- helps hypercalcuria –> decreasing excretion of Ca decreases incidence of kidney stones
Adverse effects:
- competition with uric acid secretion –> gout
- hypokalemia
- 2ndary hyperaldosteronism
- hyperglycemia/glucosuria
- hyperlipidemia
- allergies
High ceiling:
Describe the site and mechanism of action at the nephron, role in the treatment of heart failure, adverse effects - especially as it relates to effects on plasma electrolytes, and loop (high ceiling) of aldosterone antagonists
Mechanism at nephron:
- aldosterone inc number and activity of Na and K channels and Na/K ATPase –> inc reabs of Na
- blocking aldosterone receptor dec Na reabs and dec K excretion
Role in treating HF:
- anti-remodeling –> dec hypertropy and fibrosis
- K-sparing (helps with loop diuretics and etc.)
- treat hypertension
Adverse effects:
- hyperkalemia
- endocrine abnormalities (gynecomastia) with spironolactone via block of androgen receptor
High ceiling:
Describe the site and mechanism of action at the nephron, role in the treatment of heart failure, adverse effects - especially as it relates to effects on plasma electrolytes, and loop (high ceiling) of Na channel blockers
Mechanism at nephron:
- at collecting tubules, Na reabs and K excreted
- Na channel blocker dec Na reabs
Adverse effects:
High ceiling:
Describe renin-angiotensin-aldosterone system (RAAS) and the contribution of chronic RAAS activation to the underlying pathology of heart failure
- when low blood flow to kidneys –> kidneys produce renin –> renin converts angiotensinogen to angiotensin1 –> ACE converts AT1 to AT2 –> AT2 leads to vasoconstriction and the production/secretion of aldosterone –> inc TPR and Na/H2O retention –> inc BP –> inc venous return –> inc preload –> inc SV –> inc CO
Describe the target and mode of action, role in the treatment of heart failure, adverse effects - especially in relation to serum potassium and renal function, and interactions with other drugs used in heart failure of ACE inhibitors
Mechanism:
- inhibits conversion of AT1 to AT2 –> dec vasoconstriction and excess prod of aldosterone
- dec preload and afterload
- dec remodeling due to aldosterone
Role in treating HF:
- moderates remodeling
- dec preload and afterload
Adverse effects:
- cough
- angioedema
- hyperkalemia
- contraind in pregnancy
Drug drug interactions:
Describe their target and mode of action, role in the treatment of heart failure, adverse effects - especially in relation to serum potassium and renal function, and interactions with other drugs used in heart failure of ARBs
Mechanism:
- inhibit AT2 receptor AT_1
- prevents remodeling and reduces sympathetic activity
- no cough or angioedema like ACEis and there are other pathways to form AT2 besides ACE
- loss of bradykinin vasodilation like in ACEi
- doesn’t take into account AT_2 receptor
Role in treating HF:
- similar to ACEi –> dec vasoconstriction and dec Na/H2O retention
Adverse effects:
- contraindicated in pregnancy
- similar to ACEi
- no cough or angioedema
Drug drug interactions:
Describe the lead systems of the 12 lead ECG and the planes and the regions monitored by the individual leads
- 3 limb leads: I, II, III
- 3 augmented lim leads: aVR, aVF, aVL
- 6 precordial leads: V1-V6
- lateral leads: aVL and I
- inferior leads: II, III, and aVF
- frontal plane: limb and augmented limb leads
- horizontal plane: precordial leads
Explain how to determine the frontal plane QRS axis
- normal: QRS is positive in I and II
- left axis: positive in I and negative in II
- right axis: negative in I and positive in II
- indeterminate: negative in I and II
Where are P wave abnormalities best seen?
Lead II (and V1)
- in II, RA and LA are positive and combine to make a symmetric hump normally
- in V1, RA is positive and LA is negative so have a small sinusoid
- if RA is enlarged, see a more pronounced left side
- if LA is enlarged, see a more pronounce right side
Describe the ECG findings in right and left bundle branch block
RBBB:
- wide QRS are most often RBBB
- positive QRS and negative T-wave in right sided leads because delayed conduction to right side, so RV depol is not overshadowed by LV depol
- negative QRS in left leads due to delay
LBBB:
- delayed left conduction
- wide QRS away from V1 towards V6
- negative QRS in right sided leads and positive QRS in left sided leads
What are the signs of left anterior hemiblock and left posterior hemiblock
- normal (not wide) QRS
- if I and II are positive –> normal
- if I positive and II negative (and III negative) then LAD and have LAH
- if I negative and II positive (and III positive ) then RAD and have LPH
Distinguish right and left ventricular hypertrophy on the ECG
RVH:
- large R waves in V1 and V2
LVH:
- add neg peak in V1 (S wave) to peak of V5/V6; if >40 then LVH
- or just have really high QRS in V5 and V6
Identify the ECG findings in acute coronary syndromes and pericarditis
- pericarditis has diffuse ST elevation
- MI has ST elevation in specific regions
- ischemia has ST depression on high O2 demand
- subendocardial ST depression with no Q wave
- transmural infarct ST elevation and Q wave
- T inversion –> ischemia or hypertrophy or RBBB
- Q waves in at least 2 adjacent leads –> transmural necrosis
- long QT –> electrolyte imbalance
Describe aortic and pulmonic valve anatomy and function
Aortic valve:
- between LV and rest of body
- prevents backflow from body back into LV
Pulmonic valve
- between RV and pulmonary artery
- prevents backflow from lungs/pulmonary artery into RV
Describe the cause, presentation/PE findings, and treatment for aortic stenosis
Cause:
- aortic valve was many annuli
- rheumatic (calcified
- calcific aortic stenosis
- bicuspid (congenital)
Presentation:
- dec AV opening during systole –> LV outflow obstruction
- inc in LV pressure to overcome narrowing of AV
- dyspnea on exertion
- exertional syncope or lightheadedness
- exertional angina
- harsh, cresc-decres systolic murmur over right upper sternal border
- worse if mid to late peaking murmur or if S2 is soft or if slow rate in rise of carotid pulse
Treatment:
- treat as soon as you see symptoms
- monitor/check with PE, echo, and cardiac catheterization
- drugs are complicated (diuretics dec preload, but with AS, kind of want preload)
Describe the cause, presentation/PE findings, and treatment for bicuspid aortic stenosis
Cause:
- cusp fusion in development with loss of elastic fibers
- altered matrix structure (smooth muscle detachment, MMPs, loss of structure and elasticity)
- AD inheritance
Presentation:
- aortic stenosis
- aortic insuff
- endocarditis
- aortic dilation
- aortic aneurysm
- aortic dissection
- similar to calcific stenosis (angina, syncope, SOB)
- LVH
- systolic ejection murmur
- doming during systole
Treatment:
- monitor via echo
- aortic valve replacement
- screen 1st deg family members
Describe the cause, presentation/PE findings, and treatment for calcific aortic stenosis
Cause:
- similar risk factors as atherosclerosis
- displacement of elastic lamina
Presentation:
- angina, syncope, SOB
- systolic ejection murmur
- narrow split in S2
Treatment:
- check with echo
- AV replacement
Describe the cause, presentation/PE findings, and treatment for aortic regurgitation
Cause:
- aortic valve disease (rheumatic, endocarditis, degenerative, congenital)
- aorta disease (dissection, atherosclerosis, marfan’s, syphilis)
- insufficient valve closure so that blood flows backwards into LV from aorta during diastole
- aortic root dilation and bicuspid aortic valve and rheumatic disease
Presentation:
- austin-flint (high pitched) murmur
- rapid/forceful carotid pulse
- diastolic blanching of nail bed
- bobbing head
- LV dilation and dysfunction
- dyspnea, pulm edema, orthopnea
- longer diastolic murmur –> more severe
Treatment:
- AV replacement
Describe the cause, presentation/PE findings, and treatment for pulmonic stenosis
Cause:
- congenital
Presentation:
- PS –> RVH –> RV enlargement and failure
- exertional dyspnea, angina, syncope
- peripheral edema
- systolic ejection murmur at left upper sternal border
Treatment:
- balloon valvuloplasty
Describe the cause, presentation/PE findings, and treatment for pulmonic insufficiency
Cause:
- infection, rheumatic, carcinoid, congenital
- pulm artery dilation, pulm hypertension
Presentation:
- RV volume overload
- RV dysfunction
- atrial and ventricular arrhythmias
- early diastolic murmur over 2nd and 3rd left intercostal spaces
- may inc in intensity with inspiration
- systolic ejection murmur at left upper sternal border due to inc RV SV
Treatment:
- if asymptomatic, then fine
Describe the cause, presentation/PE findings, and treatment for mitral stenosis
Cause:
- rheumatic fever
- strep infection cross reaction
- calcified commissures
- often with mitral regurg
Presentation:
- loud S1 and S2 with opening snap after S2 and diastolic rumble
- systolic murmur with mitral regurg
- inc pressure in LA, lungs, right heart
- dyspnea
- hemoptysis
- pulm hypertension
- right sided HF (edema, ascites)
- afib
- stroke
- EKG shows LAE, RVH if pulm hypertension, maybe afib
- echo shows restricted opening of MV during diastole
Treatment:
- balloon valvuloplasty
- beta blockers to slow HR
- MV replacement
Describe the cause, presentation/PE findings, and treatment for mitral regurgitation
Cause:
- MV doesn’t close so blood flows backwards from LV to LA during systole
- myxomatous –> mitral valve prolapse
- endocarditis
- cardiomyopathy, myocarditis
Presentation:
- holosystolic murmur at apex radiating to axilla
- CHF symptoms
- mitral prolapse (mid systolic click and late systolic murmur)
Treatment:
- diuretics for CHF
- afterload dec (ACEi, ARBs)
- mitral valve repair/replacement
Describe the cause, presentation/PE findings, and treatment for tricuspid insufficiency
Cause:
- functional (2ndary to annular dilation and leaflet tethering in RV dilation from volume overload)
- rheumatic disease, endocarditis,
Presentation:
- JV distension with v wave
- hepatomegaly
- holosystolic murmur of tricuspid regurg along sternal border inc with inspiration
- fatigue
- edema
- dyspnea
Treatment:
- treat underlying causes of RV pressure/overload
- diuretics
- tricuspid repair/replacement
Describe the cause, presentation/PE findings, and treatment for tricuspid stenosis
Cause:
- rare
- rheumatic heart disease
- congenital
- RA tumors
Presentation:
- dyspnea
- edema
- often with mitral stenosis
Treatment:
- diuretics
- surgery
Describe common cardiac symptoms and conditions
- SOB at rest or with exertion
- irregular heart beat
- faintness of dizziness
- swelling in feet or hands
- awaking from sleep with SOB
- difficulty sleeping when flat
- leg pain with activity
- stroke
- chest pain/pressure
- passing out
- blue lips/digits
Describe chest pain due to cardiac ischemia also known as angina pectoris
causes:
- cardiac - CAD, AV disease, pulm hypertension, MV prolapse, pericarditis
- vascular - aortic dissection
- pulm - pulm embolism, pneumonia, pleuritis, pneumothorax,
- msk - arthritis, spasm, bone tumor
- neural - herpes zoster
- GI - ulcer, bowel disease, pancreatitis
- anxiety/depression
mechanism:
- supply-demand mismatch in coronary arteries –> hypoxia in myocardium –>
presentation:
- diffuse retrosternally
- left arm, jaw, back
- aching, dull, pressing, squeezing
- mild to severe
- lasts for minutes
- worse with effort (not better with posture)
- better with rest
Describe the causes and presentation of dyspnea
Causes:
- cardiac - LVHF, mitral stenosis
- pulm - pulm embolism, pulm hypertension, asthma
Presentation:
- orthopnea - SOB when flat
- PND - SOB that wakes when sleeping
- dyspnea on exertion - SOB while walking
Describe friction rub due to pericardial disease and the heart sounds heard
- pericarditis –> ventricles rub against pericardium
- rough raspy sound
Describe the heart sounds heard during aortic regurgitation
- diastolic murmur heard along left sternal border
- systolic murmur heard in aortic area
- diastolic pressure falls due to lowered resistance and inc dilation of arterioles
- carotid pulsing is visible
- quincke’s pulse (blanching and pulse in fingernails)
- does not vary with inspiration
Describe the heart sounds heard during aortic stenosis
- aortic valve opening is smaller
- inc in LV pressure
- murmur occurs with pulse upstroke and is systolic
- distinct sound in S2
Describe the heart sounds heard during hypertrophic cardiomyopathy
- similar to stenosis –> hear a rough murmur followed by a distinct second heart sound
- S1 and S2 merge into one plateaued sound
Describe the heart sounds heard in mitral regurgitation
- plateau murmur (less harsh) at apex
- see movement of stethoscope on systole
- S3 - mid-diastolic murmur
- in mitral valve prolapse –> left late systolic murmur and mitral click late in systole
Describe the heart sounds heard in mitral stenosis
- rheumatic heart disease
- poor filling of LV due to MV narrowing
- opening snap that immediately follows S2
Describe the heart sound S3
- occurs after S2 mid diastole (ken-tu-cky)
- heard with bell in LLD
- sign of LV volume overload
Describe the heart sound S4
- occurse right before S1 at end of diastole
- sign of a stiff LV
- LV is stiff and aorta pushing against stiff LV makes that sound during atrial contraction
What would a systolic ejection murmur indicate?
- aortic or pulmonic stenosis
- crescendo-decrescendo
What would a pansystolic or holosystolic murmur indicate?
- mitral or tricuspid regurgitation
- uniform throughout S1 to S2
What would a late systolic murmur indicate?
- mitral valve prolapse
What would an early diastolic murmur indicate?
- aortic regurgitation
- decrescendo
- high pitched
What would a mid to late diastolic murmur indicate?
- mitral stenosis
- opening snap followed by decrescendo murmur that intensifies at end of diastole with atrial kick
Name the most common primary cardiac neoplasms in (a) infants/children and (b) adults
a) rhabdomyoma: benign skeletal muscle cell tumor
b) angiosarcoma: malignant tumor of blood vessels
Name the most common location and possible complications of a cardiac myxoma
- usually in LA
- mitral valve involvement
- can embolize
- can cause syncope of sudden death
Identify the types of organisms that may infect the myocardium
- viral: coxsackie virus
- bacterial: chlamydiae, rickettsiae
- fungal: candida
- parasitic: protozoa, helminths
Identify at least one autoimmune disease that can affect the heart and the areas of the heart that may be affected
- collagen vascular disease/connective tissue disease
- heart involved as pat of systemic disease
- can involve pericardium, myocardium, endocardium
- can have vessel inflammation –> vasculitis –> infarcts
Give examples of substances that may be responsible for toxic cardiomyopathy
- meds: adriamycin (used for chemo)
- exogenous substances: - ethanol, cobalt
Identify the disease where proteins deposit around blood vessels and in organ parenchyma. Name a malignancy commonly associated with this disease process
- amyloidosis: protei deposition in blood vessels and organ parenchyma
- usually with plasma cell neoplasm
- wax like consistency of organs
Define the following terms: myocarditis, primary cardiomyopathy and secondary cardiomyopathy
primary cardiomyopathy:
- anatomic or metabolic myofiber abnormality
- dilated, hypertrophic, or restrictive CM
secondary cardiomyopathy:
- ischemia
- hypertension
- valve disease
- pericardial constriction
Give examples of causes of restrictive cardiomyopathy
- impairment of compliance –> diastolic dysfunction
- idiopathic, amyloidosis, radiation induced fibrosis
- pericardial constriction
- problem with heart relaxing, but not necessarily due to hypertrophy
For hypertrophic cardiomyopathy, dilated cardiomyopathy, and restrictive cardiomyopathy, describe the macroscopic appearance of the heart, the functional problem and the prevalence of genetic mutations associated with that condition
HCM:
- macroscopic: thick heart and cannot relax well; hypertrophic disarray
- functional problem: thickened LV wall; septum can be more thicker and obstruct outflow
- genetic mutations: 50-100% due to genetic mutations (myosin binding protein C, beta myosin heavy chain, cardiac troponin T)
DCM:
- macroscopic: LV gets really dilated –> inc wall stress so cannot pump as well
- functional problem: impaired contractility
- genetic mutations: 30-40% have associated mutations (desmin, dystrophin, sarcoglycans, lamin A/C)
RCM:
- macroscopic: amyloid deposition, radiation induced fibrosis
- functional problem: cannot relax during diastole
- genetic mutations: acquired, not usually genetically linked
What is cardiac myxoma?
- benign neoplasm
- common in teens and adults
- LA more often than RA
- mitral valve involvement
- can embolize
Discuss the effects of systemic hypertension
- affects left heart
- sustained afterload –> concentric hypertrophy of LV
- atherosclerosis
- aneurysm
- renal disease
Discuss the effects of pulmonary hypertension.
- affects right heart
- usually caused by LHF
- see concentric hypertrophy if afterload increased in pulmonary circuit
- see congestion of liver and peripheral edema
Define cor pulmonale and be able to give examples of underlying causes
- when pulmonary dysfunction/fluid build up leads to right sided heart failure
Discuss the incidence and complications of a bicuspid aortic valve.
- fusion of 2/3 leaflets in aortic valve
- happens in .5-2% of pop with M>F
- can cause reduced outflow –> LVH
- increased turbulence –> valve thickening and stenosis
Identify the most common causes of aortic stenosis in patients 70 years of age
- bicuspid 70
Describe the key features of rheumatic heart disease, including: changes to valve leaflets and chordae tendinea, and effects on valve function
- post-infection AI response
- pancarditis
- endocarditis: valve damage –> fibrosis –> vegetation formation on valves
- myocardium: myocarditis
- pericardium: fibrinous pericarditis
Identify the most commonly affected valves in rheumatic heart disease
- mitral and aortic valve disease
Distinguish the two major classes of cardiac valve vegetations.
1) sterile/non-bacterial:
- thrombus formation on valve
- damaged valve
- may lead to embolism, valve function deficits, potential for infection
Describe the possible complications of endocarditis.
- inflammation of endocardium (valves) –> fibrosis
- MV > AV
- fibrosis, fusion, calcification of leaflets and cusps
- fibrosis, fusion, shortening of chordae tendinae
- valves can’t open (stenosis) or close (regurg) –>HF
- susceptible to infective endocarditis
Describe the clinical presentation and possible outcomes of acute myocarditis
Presentation:
- viral cause usually
- young age
- resp or GI problems
- fever, angina, arrhythmia, HF
- lymph infiltrations of myocytes –> damage to myocytes
List the anatomic classes and features of cardiomyopathies
HCM:
DCM:
- myocardial dilation with compensatory hypertrophy
- low systolic function
- usually idiopathic
- RAAS act leads to remodeling
- volume overload
- dyspnea, orthopnea, PND
- S3 gallop due to very compliant LV
- treat with beta blockers, ACEis, and ARBs, and AAs
RCM:
Describe the causes, pathophysiology and management of hypertrophic cardiomyopathy
Causes:
- 50-100% genetic
Pathophys:
- hypertrophy
- myocyte disarray
- sarcomeres added in parallel –> concentric hypertrophy- septum more enlarged
- high EF
- outlflow obstruction
- DOE, angina,
- systolic murmur that gets louder with standing/valsalva
Management:
- avoid overexertion
- beta blockers, verapamil
- surgical myomectomy of septum
- alcohol ablation of hypertrophic cells
- ICD
- transplant
Describe the etiologies and clinical presentation of restrictive cardiomyopathy
- normal to reduced ventricular volume
- normal ventricular wall thickness
- amyloidosis and sarcoidosis
