CVR week 2 Flashcards
the myocardium, main components:
contractile tissue
connective tissue
fibrous frame
specialsied conductive system
describe the process of excitation contraction coupling?
An electrical event in the sarcolemma of the cardiac myocyte initiates the sliding of the myofilaments, resulting in contraction.
Excitation-contraction coupling begins when the action potential depolarizes the cell and ends when ionized calcium (Ca2+) that appears within the cytosol binds to the Ca2+ receptor of the contractile apparatus. Movement of Ca2+ into the cytosol is a passive (downhill) process mediated by Ca2+ channels. The heart relaxes when ion exchangers and pumps transport Ca2+ uphill, out of the cytosol.
features of the myocardial cell
- filled with cross-striated myofibrils
- many mitochondria
- plasma membrane regulate excitation-contraction couply and relaxation
- plasma membrane seperate cytosol from extra-cellular space and sarcoplasmic reticulum
myocardial metabolism:
Relies on free fatty acids during aerobic metabolism (efficient energy production).
During hypoxia, there is no FFA metabolism, thus anaerobic metabolism ensues. This relied on metabolising glucose (anaerobically) producing energy sufficient to maintain the survival of the affected muscle without contraction.
Ultrastructure of myocardial cells:
Contractile proteins are arranged in a regular array of thick and thin filaments (The so called Myofibrils).
A-band: the region of the sarcomere occupied by the thick filaments.
I-band: is occupied only by thin filaments that extend toward the centre of the sarcomere from the Z-lines. It also contains tropomyosin and the troponins.
Z lines bisect each I-band.
what is a sarcomere?
The sarcomere: the functional unit of the contractile apparatus,
The sarcomere is defined as the region between a pair of Z-lines,
The sarcomere contains two half I-bands and one A-band.
what is the sarcoplasmic reticulum? what is the sarcolemma?
The sarcoplasmic reticulum is a membrane network that surrounds the contractile proteins,
The sarcoplasmic reticulum consists of the sarcotubular network at the centre of the sarcomere and the subsarcolemmal cisternae (which abut the T-tubules and the sarcolemma).
The transverse tubular system (T-tubule) is lined by a membrane that is continuous with the sarcolemma, so that the lumen of the T-tubules carries the extracellular space toward the center of the myocardial cell.
Contraction of sarcomere:
Sliding of actin over myosin by ATP hydrolysis through the action of ATPase in the head of the myosin molecule.
These heads form the crossbridges that interact with actin, after linkage between calcium and TnC, and deactivation of tropomyosin and TnI.
myosin
2 heavy chains- also responsible for heads
4 light chains
heads are perpindicular at rest, bend towards centre during contraction
actin
globular proetin
double stranded helix
both form the F actin
tropomyosin
Elongated molecule, made of two helical peptide chains.
It occupies each of the longitudinal grooves between the two actin strands.
Regulates the interaction between the other three!
troponin- 3 types
Types of troponin:
I: with tropomyosin inhibit actin and myosin interaction.
T: binds troponin complex to tropomyosin.
C: high affinity calcium binding sites, signalling contraction.
The latter bond, drives TnI away from Actin, allowing its interaction with myosin
titin
titin molecules anchors myosin to Z-line
sumamry of muscle contraction:
1- Ca++ enter the cell through Ca++ channels on sarcolemma during depolarization(phase 2) and triggers release of Ca++ by terminal cisternae. =(Ca++ induced Ca++ release)
2- Ca++ binds to troponin-C inducing a conformational change in the troponin complex. (Ca+ binds to troponin, so troponin releases actin. The free actin can now bind to myosin.)
3- Myosin heads bind to actin, leading to cross-bridge movement(=sliding) (requires ATP hydrolysis) and reduction in sarcomere length. (muscle contraction)
4- Ca++ is re-sequestered(Ca++ reuptake) by sarcoplasmic reticulum by sarco- endoplasmic reticulum calcium ATPase (SERCA) pump.
5- Ca++ is removed from troponin-C and myosin unbinds from actin (requires ATP hydrolysis); this allows the sarcomere to resume its original, relaxed length. (muscle relaxation)
40 degree angle
projections on the myosin filament
Cardiac Cycle Phases:
LV contraction:
LV relaxation:
Ventricular Contraction- systole
Wave of depolarisation arrives,
Opens the L-calcium tubule, {ECG: Peak of R},
Ca2+ arrive at the contractile proteins,
Left ventricular pressure rises > Left artrial pressure:
Mitral Valve closes: M1 of the 1st Heart Sound,
Left ventricle pressure rises (isovolumic contraction) > aorta pressure
aortic valve opens and Ejection starts.
Ventricular Relaxation
Left venticular pressure peaks then decreases.
Influence of phosphorylated phospholambdan, cytosolic calcium is taken up into the SR.
“phase of reduced ejection”.
Aortic flow is maintained by aortic distensibility.
Left Ventricular pressure < Aotic pressure, Aotic valve closes, A2 of the 2nd Heart Sound, “isovolumic relaxation”- period of time between Aortic vakve sutting and mitral valve opening, then Mitral Valve opens
Ventricular Filling
Left Ventricular pressure < Left Atrium pressure, MV opens, Rapid (Early-phase) filling starts - passive
Ventricular suction (active diastolic relaxation), may also contribute to E filling, S3 sound
Diastasis (separation): LVentricular pressure = LAtrium pressure, filling temporarily stops. net flow is 0
Filling is renewed when Atrial contraction (augmentation), raises L Atrial pressure creating a pressure gradient. sometimes hear S4 sound- always pathological
(older people are more reliant on atrial augmentation, rely on it for roughly 40% of blood movement)
mitral valve shuts- 1st heart sound (Lub)
Physiologic vs. Cardiologic systole
Physiological:
1. Isovolumic contraction,
2. Maximal ejection
Cardiological:
1. From M1 to A2,
2. Only part of isovolumic contraction (includes maximal and reduced ejection phases)
preload and afterload
Preload: is the load present before LV contraction has started.
Afterload: is the load after the ventricle starts to contract.
starlings law:
the larger the volume of the heart, the greater the energy of its contraction and the amount of chemical change at each contraction. This eventually reaches a plateau
how do you calculate left ventricular pressure?
LV filling pressure: is the difference between LAp and LV diastolic pressure.
starlings law relavence to heart failure:
define contractility and elasticity:
Contractility (inotropic state): the state of the heart which enables it to increase its contraction velocity, to achieve higher pressure, when contractility is increased (independent of load)
Elasticity, is the myocardial ability to recover its normal shape after removal of systolic stress.
compliance and diastolic distensibility definitions
Compliance is the relationship between the change in stress and the resultant strain.(dP/dV).
Diastolic distensibility is the pressure required to fill the ventricle to the same diastolic volume.
Embryology of the heart:
what is gastrulation? name of layers?
mass movement and invagination of the blastula to form 3 layers- ectoderm, mesoderm and endoderm
what develops from the ectoderm?
Ectoderm – (outside) – skin, nervous system, neural crest (which contributes to cardiac outflow, coronary arteries)
what develops from mesoderm?
middle – all types of muscle, most system, kidneys, blood, bone
(some cells can ‘forget’ what theyre supposed to e.g. muscle in artery walls turning to bone)
what develops from endoderm?
gastrointestinal tract (inc liver, pancreas, but not smooth muscle), endocrine organs
the heart fields: what will they develop to?
FHF - (first heart field) future left ventricle, genrates sacoffold which is added to by second heart field
SHF- (second heart field) outflow tract, future right ventricle, atria
example of cardiac transcription factors?
Nkx2.5
GATA
Hand
Tbx
MEF2
Pitx2
Fog-1
transcription factors are expressed in a tissue specific manner
3 stages of cardiac formation:
formation of primitive heart tube
cardiac looping
cardiac seperation
formation of primative heart tube? how? what will it look like?
3rd week:
horseshoe shape region (called cardiogenic region) of FHF and SHF, 2 endocardial tubes form and then fuse to form a single primative heart tube
Primative heart:
top is bulbis cordis (foremsmost right ventricle and part of outflow tracts), then primative ventricle, then primative atria
cardiac looping?
bulbis cordis moves inferiorly, anteriorly to the embryos right,
primative ventricle moves to embryos left side
primitive atrium and sinus venosus move superiorly and posteriorly
cardiac septation- what does heart look like before? what occurs in cardiac septation?
currently blood flows into one common atria and one common ventricle connected by atrioventricular canal and then out of truncus arteriosus, mases of tissue called endocardial cushions grow from sides of atrioventricular canal to make 2 seperate openings called R and L atrioventricular canals
