Cvs Flashcards
Automaticity
initiate contraction independent of external stimuli
Rhythmicity
regular beats
Automaticity and Rhythmicity cause
Due to presence of Pacemaker cells → generate spontaneous & regular action potentials.
pacemakers their charge speed
SAN cells (90-105/min Normal pacemaker (fastest)→ o Vagal tone →↓ SAN rate
• AV node cells (60/min) in failure of SAN
• Purkinje cells (40/min) in failure of AVN. (idioventricular rhythm)
pacemakers their charge speed and define
SAN cells (90-105/min Normal pacemaker (fastest)→ o Vagal tone →↓ SAN rate
• AV node cells (60/min) in failure of SAN
• Purkinje cells (40/min) in failure of AVN. (idioventricular rhythm)
slow response action potential phase 4 name and define
Pre polarization
At – 60 mv:
A- Opening of funny Na+ channels→Causes inward Na+ (HCN?)
B- Activation of Na+-Ca++ exchanger due to spontaneous release of Ca++ from SR
• → move 1 Ca++ out for 3 Na+ in → Causes inward Na+
At -50 mv: Opening of T-type Ca++ channels →Cause inward Ca++
slow response action potential phase 4
Prepotential
At – 60 mv:
A- Opening of funny Na+ channels→Causes inward Na+ (HCN?)
B- Activation of Na+-Ca++ exchanger due to spontaneous release of Ca++ from SR
• → move 1 Ca++ out for 3 Na+ in → Causes inward Na+
At -50 mv: Opening of T-type Ca++ channels →Cause inward Ca++
slow response action potential phase 0 name and define
Depolarization
At -40 mV = firing level
1. Closure of funny channels & T-type Ca++ channels
2. Opening of L-type Ca++ channels Causes inward Ca++ current→ cause slow depolarization 3. Gradual opening of DRK+ channels
slow response action potential phase 3
Repolarization
1. Opening of DRK+ channels →cause outward K+
2. Closure of L-type Ca++ channels
3. Repolarization to -60 mV→ cause inactivation of K channel & Activation of funny channel
Factors affecting rate of SA nodal discharge= chronotropy= heart rate (rhythmicity) sympathetic
Mechanism:
✓ Sympathetic (norepinephrine)
✓ Bind β1 receptors →↑ c-AMP →
✓ ↑ funny current
1. Earlier depolarization starts earlier
2. ↑slope of phase 4.
Reach threshold in shorter time
Factors affecting rate of SA nodal discharge= chronotropy= heart rate (rhythmicity) para sympathetic
Mechanism:
✓ Vagus (acetylcholine)
✓ Bind muscarinic receptors →↓ c-AMP→ ✓ ↓ funny current.
1. Delayed depolarization
2. ↓slope of phase 4.
Reach threshold in longer time
Acetylcholine activates K+ channels (KAch)
Effect of catecholamines on SA nodal discharge
HR inc
Effect of body temp on SA nodal discharge
10 (fever) →↑ HR 10 beats/min.
Effect of Ca++ channel blocking drugs
↓ HR
Effect of hyperkalemia on SA nodal discharge
↑ conductance → ↓ slope of phase 4 → ↓ HR
Velocity of conduction depends on what
1- Number of gap junction (↓ conductance ability in hypoxia or ↑free Ca++ )
2- Amplitude & speed of upstroke of A.P.
Factors affecting rate of conduction(Autonomic)
Sympathetic→↑ conductance → ↑ velocity
Parasympathetic→dec conductance → dec velocity
, Digitalis→↓ velocity
Cardiac Myocyte Action potential phase 4
RMP)
K+ moves out via IRK
Cardiac myocyte phase 0
Depolarization from -90 to + 20mv
1. Inactivation of IRK
2. Opening of voltage gated Na+-channels: inward Na+ (Fast response )
Cardiac Myocyte phase 1
rapid small
repolarization
1. Closure of voltage gated Na+ channels
2. Opening of special K+ channels 3. Opening of Cl- channels
Cardiac myocyte phase 2
Plateau (around zero mV)
200 msec
Balance between
1. Outward positive via DRK+ channels 2. Inward positive via
A- Long lasting Ca++ channels
B- ↑Activity of Na+-Ca++ exchanger: Move 1 Ca++ out for 3 Na+ in
Cardiac myocyte phase3
Rapid late repolarization
1. Closure of long-lasting Ca++ & ↓ activity of Na+-Ca++ exchanger 2. Delayed rectifier K+ channels → causes outward K+
As membrane potential approaches RMP:
• Closure of DRK
• ↑Activity of inwardly rectifying K+ channels: →to reach -90 mV
Absolute refractory period (ARP)
Response and phase
No response to nay stimulus Cause: inactivation of Na+ ch
Phases 0, 1, 2, and part of phase 3 to -50 mv)
Relative refractory period (RRP) Response and phase
Respond to supra- threshold stimulus.
Follows ARP to -75 mv
supernormal period response and phase
Respond to weaker stimulus → arrhythmias
Follows RRP
to fully repolarization
Importance of refractory period
Prevents tetanic contractions (not suitable for pumping) As it occupies
whole systole and early diastole
Effect of ischemia on electrical activity of the heart
Ischemia cause accumulation of K+ in ECF, due to:
A- Opening of KATP channels & Inhibition of Na+-K+ ATPase pump
2. Accumulation of K+ in ECF cause Membrane depolarization
3. Membrane depolarization →↓decreased number of active Na+ channels →↓Slope of phase 0.
4. ↓Slope of phase 0 & ↑intracellular Ca++→↓conduction velocity
Relationship between Action potential &mechanical response
• Contraction
• Contraction after start of depolarization maximum at end of plateau
Relationship between Action potential &mechanical response. Relaxation
Relaxation First half with Repolarization (phase 3)
Explain Excitation contraction coupling
Membrane depolarization → open L-type Ca++ channels
2- Ca++ entry → open ryanodine sensitive- calcium channel on SR “Calcium- induced Calcium release”
3- Ca++ binds Troponin-C →contraction
4- Relaxation via removal of calcium from cytoplasm:
a. SERCA→ actively reuptake Ca++
b. Na+-Ca++ exchanger: move Ca++ out c. Calcium pump
5- Force of cardiac contraction (notropic state) depends mainly on Ca++
Explain Excitation contraction coupling
Membrane depolarization → open L-type Ca++ channels
2- Ca++ entry → open ryanodine sensitive- calcium channel on SR “Calcium- induced Calcium release”
3- Ca++ binds Troponin-C →contraction
4- Relaxation via removal of calcium from cytoplasm:
a. SERCA→ actively reuptake Ca++
b. Na+-Ca++ exchanger: move Ca++ out c. Calcium pump
5- Force of cardiac contraction (notropic state) depends mainly on Ca++
Positive inotropic mechanisms
Sympathetic
norepinephrine) or catecholamines → ✓ bind β1 receptors →↑c-AMP→
✓ Activates Protein Kinase → phosphorylates
a. L-type Ca++ channel
b. calcium release channel on SR
Negative Inotropic Mechanisms:
Parasympathetic
(acetylcholine) →
✓ Bind muscarinic receptors (M2) → ↓c-AMP
Positive inotropic mechanisms Drugs
Digitalis→ inhibits Na+-K+ ATPase →↑ Na+. Na+-Ca++ exchanger move 3Na+ out for 1Ca++ in. →↑Ca++ inside myocytes.
• Xanthine (caffeine)→ inhibit breakdown of c-AMP→↑c-AMP conc.
Negative Inotropic Mechanisms: Drugs
• Calcium channel blockers (dihydropyridine) inhibit L-type Ca++ channels →↓ Ca++ entry
• Anesthetic drugs
Regulation of Myocyte Relaxation (lusitropy)
1- Sympathetic / catecholamine
bind β1 receptors →↑ c-AMP →activate protein kinase
↑Activation of SERCA → rapid removal of Ca++ ↓binding of Troponin to Ca++.
Sympathetic causes strong contraction ad rapid relaxation
Regulation of Myocyte Relaxation (lusitropy) Ischemia
↓activity of Ca pump →↑ intracellular Ca++→ inhibits relaxation
Myocardial ischemia causes weak contraction and poor relaxation.
Effect of changes in afterload:
On degree of shortening: (inverse relation). ↓by ↑afterload
B- On velocity: inverse relation
Zero velocity. Maximum velocity (Vmax)
When load ≥ maximum tension When load is zero
(Contraction remains isometric).
Effect of changes in inotropic state: positive inotropic
On degree of shortening shifts active length-tension relationship upwards and left.
B- On velocity → Shifts load-velocity curve upwards and right→↑ velocity
Effect of changes in preload:
A-On degree of shortening direct relation
B- On velocity
↑preload → shifts load-velocity curve upwards and right →↑ velocity
Effect of ↑frequency: staircase phenomenon” or “treppe”
o ↑frequency → ↑ force of contractions till reach plateau o Cause: Ca++accumulation
Stroke volume (SV): depend on
preload, afterload, inotropic state
Changes in HR are more important than changes in SV.
Cause: In untrained person, HR ↑100% to 200% during exercise
Doubling HR alone from 70 to 140 beat/min
(by artificial pacemaker or arrhythmias) →
↓ SV (due to shortening of diastolic time & filling)
→ no change in CO
↑HR alone > 150/min→
Marked↓ in SV →↓ CO.
(↑HR cannot compensate for ↓in SV)
↓HR alone < 60/min→
↓ CO
(↑SV cannot compensate for ↓ HR) (Limited capacity)
During exercise (in physiology) Doubling HR
doubling CO due to ↑ SV
Effect of changes in preload on SV and define preload
degree of stretching (sarcomere length) before contraction.
• Measured by EDV
• EDV depends on VR.
B- ↑VR→↑ EDV→↑ SV = direct relation = Starling’s law=
“heterometric autoregulation” → matches SV with VR.
C- In pressure-volume loop
• Ventricle start contraction at higher EDV (2a) and reach the same ESV = ↑ width → ↑SV. D-in performance of isolated cardiac muscle
↑preload →↑ amount and velocity of shortening
Factors affecting preload:
- ↑VR (most important factor )
- Strong Atrial contraction →↑preload.
- ↑Heart rate → ↓diastolic time →↓preload
- ↓Ventricular compliance (myocardial infarction) →↑slope of EDVPR→ ↓ preload
Effect of changes in preload on SV
Effect of Afterload on Stroke Volume and define Afterload
Afterload= aortic pressure for left ventricle/ pulmonary pressure for right ventricle
➢ ↑afterload → shifts relationship between EDV and SV downward →↓ SV
➢ In Pressure-volume loop:
• Ventricle start contraction at the same EDV and
reach higher ESV = ↓SV
➢ in performance of isolated cardiac muscle:
↑afterload → ↓ amount and velocity of shortening →↓SV
Effect of Inotropic State on Stroke Volume
➢ + ve inotropic → shifts relationship between EDV and SV upward → ↑SV
➢ In pressure-volume loop:
• + ve inotropic shifts ESPVR upwards & left
• Ventricle start contraction at the same EDV and reach lower ESV
➢ in performance of isolated cardiac muscle: + ve inotropic →↑ amount and velocity
End Diastolic Volume =
volume of blood at end of diastole.
ESV:
volume of blood at end of Systole.
• Stroke volume:
volume of blood pumped by each ventricle/ beat
• Cardiac Output :
volume of blood pumped by each ventricle /min.
•
Cardiac index:
CO/ m2
Cardiac Output increased in
Exercise (700%)
Excitement & anxiety (100%) Pregnancy
Cardiac Output decreased in
Rapid arrhythmia
Heart failure
standing from supine position
