Physiology 12.5.12 Regulation of Cardiac Contraction Flashcards
Characteristics of Cardiac Muscle (general- 7)
Functions as a synctium
Intercalated disks (gap junctions, connexons)
Very rich in mitochondria- continuous supply of ATP for contraction
Rich capillary supply- about one capillary per fiber-short diffusio distance for oxygen ,CO2, substrates, waste products
T-tubular system- importatnt in excitation-contraction coupling, ready acceess to interstitial flulid
network of SR- regulates intracelular Ca
Presence of SR-T tubule junction
When does Ca enter the cell>
during the PLATEAU PHASE of the cardiac AP
What deos Ca release trigger?
triggers release of additional Ca from the SR
What happens to Ca that is released from SR
Ca binds to Troponin C, leading to contraction of myofibrils
What happens to Ca during resting phase to lead to relaxaction
SR begins to pump Ca into SR via Ca-ATPase (causing relaxation)
What is Phospholambam
It nroamlly inhibits Ca-ATPase activity.
What do catecholamines lead to (what pathway)
increase and AC –> Increase in cAMP –> increases in cAMP-PK
What deos caMP phosphorylate
Phosphorylates Ca cahnnels (more Ca entry) adn phospholamban (relieving the inhibition of ATPase and producing more and faster Ca uptake by SR)
What does increase in cAMP lead to?
leads to
- increased speed of contraction
- Increased speed of relaxation
What do cardiac glycosides do?
They inhibit Na-ATPase (Na pump) and elevate intracellular Na
This reduces Na influx and Ca extrusion via Va/Ca exchange, resulting in elevated intracellular Ca
Inhibition of Na pump leads to increased CONTRACTILITY
What is an example of Cardiac Glycoside? What is is used to treat?
DIGOXIN
used to treat heart failure
What is Cardiac Output
Heart Rate x SV
What are intrinsic factors/regulation that affect heart (3)
Contraction of denervated heart
Starling’s Law
Rate-induced Regulation
What are extrinsic factors/regulations that affect herat (4)
Nerve control of heart beat
Sympathetic
parasympathetic
other hormones (O2, CO2, pH)
What happens when Phospholamban in phosphorylated (by increase in cAMP by catecholamines)
increase Ca ATpase activity –> Ca enters SR faster –> increase velocity of muscle relaxation
What can incerase cardiac contractility
Beta adrenergic agonist–> increase Ca in cell –> cardiac glycosides increase force of contraction)
What is the Frank-Starling’s law of the heart
Tension developed by heart is dependent on preload (or the end-diastolic volume or length of the tissue)
The greater the length (i.e. caused by stretch) ,the greater the tension
no neural input needed
Rate-induced increase in the force of contraction (intrinsic)
demonstrate changes in the F of contraction produced by changes in heart rate
In each case, underlying mechanism invovles chagnes in intracellular Ca concentration
What is the staircase or Treppe phenomenon?
i.e. exercise, HR and Contractility increase togethr.
It is important to note that increasing the HR increases the F of contraction independently of any simultaneous beta adrenergic-induced increase in contractiltiy.
How does increasing the HR increase the force of contraction (2 mechanisms- Ascending or positive Staircase)
- More rapid heart rate means more plateaus (phase 2 of cardiac cycle AP) per unit time, and Ca2+ enters cell every plateau
- If HR is suddenly increased, magnitude and duration of inward Ca current increase with each AP until new steady state is acheved. These mechanimss elevate intracellular Ca2+ that is available to the contractile proteins –hence a greater F of contraction (baseline Tension increase)
Why is it th 1st beat smaller?
when Incerase frequency, 1st beat smaller due to pre-mature contraction (not as much Ca to pump heart)
What is Premature Contraction and Post-extrasystolic potentiation
When a premature extra-systole occurs, F developed by the ventricle is smaller than normal and F developed during the subsequenct contraction is greater than normal (post-exxtra-systolic potentiation)
What causes the diminished force of premature contravtion
involves Frank-starling mechanism
Premature contraction occurs when resting fiber length was smalle (incomplete filling had occured)
Post
What causes the augmented contraction of post-extra-systolic contraction
Post-extra-systolic contraction occurs whent eh resting fiber was especially long (extra filling had occurred during the COMPENSATORY PAUSE)
What can explain the weak premature contraction
When premature contraction cocurred- smaller than normal amt of Ca was released from SR since it takes about 500 msec for all of the Ca released during, and taken up after, the previous contraction to again become available for release
Why is postextrasystolic contraction larger than normal
pool of releasable Ca is greater than normal, b/c Ca in SR had accumulated ruign last two heartbeats
What is PVC
premature ventricular contraction
most common ventricular arrythmias
sensation of skipped beat, pauses, or palpitation
What happens to HR after a carotid massage
carotid massage stimulates barorecepotr and produces increased Vagal Activity, leading to temp cessation of heart beat
What does the heart beat look like after temporary cessation after carotid massage
the following heart beat after cessation shows greater force of contraction
this is due to changes in the availability of Ca2+ to teh contractile proteins
Where does Sympathetic Nervous control come from (part of spine)- EXTRINSIC CONTROL
Stellate ganglia
Middle cervical ganglia
postganglionic neuron -NE
What does PS
dorsal motor nucleus
nucleus amiguus (in the medulla)
postganglionic neurons- ACh
What does the sympathetic NS innervate
all segments of the heart, pacemaker, conduction, and contractile cells
What is the effect of sympathetic stimulation on heart
Increase frequency of contract ion (in HR)
increase velocity and speed of depol through heart (I funny)
Increase contractility of heart (Ca channels phosphorylated, inc Ca)
How does sympathetic innervation affect AP graph
increase rate of rise of Phase 0
increase rate of repolarization of Phase 3 of pacemaker AP
Duration of systole is shorter
Shortening of Phase 4 (ventricular AP), shortens duartion of diastole
What is the result of a simulataneous blockade of both PS and Sympathetic input to heart
resutls in rapid heart rate (~100 beats/min)
What is Atopine? Function?
a muscarinic cholinergic antagonist (ACh blocker)
causes heart rate to increase consdierably
What s Propanolol
Beta-1 adrenergic antagonist
decreases HR only slightly
Does PS or Symp influence normal Heart Rate more?
In normal humans the intrinsic heart rate (~100 beats/min) is noramlly being restrained by PS (vagal) suppression
What does increases arterial lead to (in terms of HR)
leads to decreased HR
What is the Baroreceptor Reflex
Decrease in HR due to High ARTERIAL PRESSSURE
Where are BaroR located
located at the bifurcation of internal and external carotid arteries where nerve endings can sense the pressure of teh artery
BaroR also locaetd in Aortic Arch. Here sigal is carried by vagus nerve to brainstem area
What do ChemoR detect
sense arterial O2 pressure , and also located in same region as BaroR
What does increase in arterial P do to sinus nerve?
causes sinus nerve to fire more requently
Singal is then carreid to glossopharyngeal nerve (CN #9) to meduall where CV control center is located
What are consequences of Incrase in sinus pressure ()
- Increase vagal activity (decrease HR)
2. Decrease Sympathetic activity
What is the Brainbridge reflex?
- Acceleration of HR by increase Right ATRIAL Pressure
2. Due to stimulation of atrial R
What is a respiratory (sinus) arrythmia
in healthy indidivuals, lthe HR is Faster during inspiration than experiation
R-R is closer during inspiration
Why is heart rate faster during inspriation (2 reasons)
- Increases venous return - increases HR (Brainbridge refelx)
- Decreases return of blood to left herat, decreases SV and reduces Arterial blood pressure0 increases HR (BaroR relex)
symp activity increases and vagal activity decreases
What happens during expiration
vagal activity inc
sympathetic act decreases
What is the clinical sign of absence of sinus arrythmia
Clinical sign of deterioration of ANS
i.e. sinus arrhythmia disappears in neuropathy that develops in some long-term diabetes
What is the Valsalva maneuver?
Maneuver in which a person tires to exhale forcibly with a closed glottis (windpipe) so taht no air exits through mouth or nose
This impedes return of venous blood to heart
What are examples of Valsalva maneuver
Stenuous coughing
Straining during a bowel movement
lifting a heavy weight
How many phaes does normal response to Valsalva maneuver
4
What is phase 1 of Valsalva maneuver
Squeezing lung forces blood out of lung into left atrium causing a mild rise in SV–reflex mechanism would decrease HR intially
What is phase 2 of Valsalva maneuver
Venous return to right heart is reduced due to squeezing of the lung (pressure inside chest is increased)
This causes a fall in SV and CO–reflex mechanism would then incereas Symp NS activity increasing HR
Phase 3 Valsalva
Upon termination of maneuver, P on chest is released. This allows lung to hold more blood and temporarily reduces left ventricular return and SV–reflex mechanism would increase HR slightly
Phase 4
Venous return to right heart inc adn CO begins to inc.–HR returns to normal
What does deviation from Valsalva maneuver signify
indicate abnormal heart funciton or abnromal ANS input to heart
What are efects of Hypoxia, Inc CO2, and low pH?
Directly Decrease HR
through chemoreceptors and ventialtion increase HR
