Lecture 6 Flashcards
Heart consists of 2 Pumps?
Right and Left composed of Muscular Chambers (Atria and Ventricles) separated by Valves
Muscular Chambers of the Heart?
Atria and Ventricles separated by valves
Muscle around Left Ventricle are?
Stronger because it has greater forces to work against
Muscle around Left Ventricle are?
Stronger because it has greater forces to work against
Movement of Heart Valves is based on?
Pressure differences between Atria and Ventricle
Open Heart Valve?
Ejecting blood
Closed Heart Valve?
Filling Atria/Ventricle
Heart valves open and close in a?
Coordinated way
(Excitation-Contraction Coupling)
Muscle contraction closely follows?
Wave of depolarization (excitation) throughout Heart
When Ventricles depolarize they?
Contract
Stroke Volume?
Amount of blood ejected from Heart, based on Systolic/Diastolic volume
Cardiac Output is?
Stroke Volume x Heart Rate
End Diastolic Volume?(EDV)
Amount of blood sitting there before Ventricle contracts
End Systolic Volume (ESV)?
Small amount of blood, after blood has been pushed out
Stroke Volume is ______ - ______?
SV = EDV - ESV
Stroke is volumetric representation of?
Pulse Pressure
Increase Pulse Pressure, Increase?
Stroke Volume
Venous Return?
Amount of blood returning to right atrium per minute
If blood not returned to right atria, Cardiac Output does?
Not venous return, blood accumulating in lungs or venous compartment
With valves closed (filling atria/ventricle), pressure develops during?
Myocardial Contraction (Isovolumetric Contraction)
When ventricular chamber pressure exceeds?
Aortic BP, valves open
Pv > Pa?
Open valve, ejection of blood
Cardiac Muscle is striated because of?
Thick (myosin) and Thin (actin) filaments
Intercalated discs between cardiac cells contain both?
Mechanical (Fascia Adherent and Desmosomes) and Electrical Connections (Gap Junctions) between cells (permits function as a syncytium)
T-tubules lie along the?
Z-Line and not the I-Bands (help propagate charge)
Sarcoplasmic Reticulum?
-Not as dense as in skeletal muscle
-Ca2+ mainly extracellular
-Terminal cistern about the T-tubules
-SERCA2a, calcium reuptake pump, is inhibited by phospholamban, and integral SR protein
SERCA2a?
Calcium reuptake pump, is inhibited by phospholamban, an integral SR protein
Mitochondria?
Abundant and occupy ~30% of Heart volume (because very metabolically active)
Cardiac Muscle has an abundance of?
Connective Tissue to prevent rupture and overstretching of Heart
Z-Line?
Point of attachment of thin filaments
Thin Filaments?
Actin, troponin (TNNC1, TNNI3, TNNT2), tropomyosin (TPM1), nebulin (scaffold for thin filament), alpha-actinic (anchors actin to Z-Line), tropomodulin (regulates length of thin filament)
Thick Filament?
Myosin, meromyosin and C-protein (scaffolds for thick filament), Titian. MHC has 2 isoforms: alphaMHC (faster velocity) and betaMHC
Titin?
Tethers myosin to Z-Line; stretch-sensor, signal transducer, and may be involved in increasing force in response to stretch (Important for Sterling’s Law)
Depolarization causes?
Calcium entry via voltage-gated Calcium Channels
Calcium entry triggers?
Calcium release from SR via Ryanodine receptors
(Calcium Homeostasis in Myocardial Cells)
Increased intracellular calcium is via?
1) Release from SR (90%) via Ca-induced Ca release channels
(majority)
2) Influx through voltage-gated “L-type” calcium channels (10%)
(Calcium Homeostasis in Myocardial Cells)
Relaxation?
Intracellular Ca pumped back into SR and also out of myocyte via CaATPase pumps and Na/Ca exchanger (SERCA at 905)
Force generated dependent on?
Cross-Bridging cycling
(Excitation-Contraction Coupling)
Cross-riding Cycle (ratchet mechanism)?
(Ca2+ proportional to cross-bridge cycling)
1) Bound ATP causes conformation change in hinge region of myosin and promotes binding to actin
2) Hydrolysis of ATP causes a conformational change in hinge region of myosin, causing movement of thin filament and shortening of sarcomere
3) After movement, ADP dissociates from myosin
4) Myosin-actin remain bound with no ATP (rigor mortis state, death)
5) ATP binding to myosin
6) ATP binding causes dissociation of myosin (ATP) from actin
Resting Tension (RT)?
Produced by “resting” biomechanics properties of cardiac tissue
Active Tension (AT)?
Produced by cross-bridge cycling
Total Tension (TT)?
RT plus AT
Lmax?
Length at which active force is maximal (increased force at particular moment)
Increased L?
Increased Tension
Force (Tension) produced with increased?
Muscle Length (Stretch)
Stretching the Heart increases?
Force of Contraction, but not by increasing [Ca++] or increased filament overlap
Frank-Starling Law of the Heart?
“Force of contraction of Heart is proportional to initial fiber length”
Length-dependent increase in force following stretch may be due to?
1) Decreased interfilament spacing (decreased space between actin + myosin) between actin and myosin, brought about by Titin, which binds both of filaments
2) Increase in sensitivity to calcium of actin-myosin complex
Increased Stretch?
Increased Tension because need more space between myosin and Z-Disk
Role of Titin?
-Spring in controlling distance between actin + myosin filaments
-Titin binds both actin and myosin
-Stretching brings the 2 filaments closer together
One mechanism to explain how preload influences contractile force is that increasing?
Sarcomere length increases troponin C calcium sensitivity, which increases rate of cross-bridge attachment and detachment, and amount of tension developed by muscle fiber
(Stretching increases sensitivity of cardiac muscle to calcium)
Stretch sarcomere with same amount of calcium will get?
Greater larger force
(Stretching increases sensitivity of cardiac muscle to calcium)
Will get greater force by being more sensitive to?
Calcium
(Heart responds to an increase in stretch)
When there’s an increase in venous return?
There’s a greater force of contraction, resulting in a greater cardiac ejection
End effect?
Input = Output
Venous Return?
Cardiac Output
(“The Heart pumps what it gets”)
Increased Venous Return = ?
Increased Venous Return = Increased EDV = Increased Stretch = Increased Force
Increased Venous Return = ?
Increased Venous Return = Increased EDV = Increased Stretch = Increased Force
If Increase amount of blood returning to RA?
Increasing EDV
Sympathetic Nervous System?
(“fight or flight”)
-Superior cervical ganglion
-Middle cervical ganglion
Parasympathetic Nervous System?
(“rest and digestion”)
Vagus (X) nerve
Sympathetic?
Increased Ca2+ release and reuptake and increased contractions
(Sympathetic or Parasympathetic)
Epinephrine/Norepinephrine?
Sympathetic
Adenylyl Cyclase will produce?
cAMP
Beta-Adrenergic stimulation enhances?
Contraction and accelerates relaxation
(Gs –> Increased cAMP –> PKA which phosphorylates)
a. ?
VGCC (CHPR) and increased calcium entry
(Gs –> Increased cAMP –> PKA which phosphorylates)
b. ?
RYR, increased calcium release
(Gs –> Increased cAMP –> PKA which phosphorylates)
c. ?
Phospholamban, removing its inhibition of CaATPase, thus increased uptake of Ca++ by CaATPase –> shortened contraction and increased rate of relaxation (lusitropic effect) due to rapid accumulation of calcium, which also increased Ca++ stores for next contraction
(Gs –> Increased cAMP –> PKA which phosphorylates)
e. ?
Troponin I, makes Ca++ dissociate from myofilaments –> decreased myofilament sensitivity to Ca++ –> relaxation
In contrast, Vagal stimulation?
ACh –> M2 –> Gi –> Decreased cAMP (decreased amplitude Ca2+ and force and increased relaxation time)
Preload dependent on?
EDV, how much pressure your ventricle has sitting in it (dependent on End Diastolic Volume)
Preload dependent on?
EDV, how much pressure your ventricle has sitting in it (dependent on End Diastolic Volume)
Factors affecting EDV/ Preload?
1) Ventricular compliance (stretch/stiffness)
2) Filling time (Heart Rate) (increased time = increased preload = increased EDV)
3) Venous Return (increased return = increased preload = increased EDV)
Afterload?
Represents forces that Heart has to work against (all sitting in Aorta that has to go out)
(ex. Systemic Aortic Pressure)
Increasing aortic pressure does not?
Decrease cardiac output until MAP > 160 mmHg
MAP?
Mean Aortic Pressure
Cardiac output remains constant?
Until MAP rises above 160 mmHg
Cardiac output remains constant?
Until MAP rises above 160 mmHg
