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Block 2 - Theme One
cadiac pump and regulation
91
Biology
Graduate
10/13/2008

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Term
Resistance to fluid flow in a vessel is directly and inversely related to what?
Definition
The length of the vessel and the viscosity, and inversely to the 4th power of radius
Term
What type of control unit can cut off blood flow to a capillary bed to modify blood flow?
Definition
Precapillary sphincters
Term
True or False: In a very metabolically active cell, like heart or lung, the capillary is a large distance away from the cells in order to create a large pool of nutrients.
Definition
False, they often abut directly on cell with essentially no diffusion distance.
Term
The constriction of arteries has little effect of flow, but constriction at ________ has a large effect on vacular resistance.
Definition
Precapillary arterioles
Term
Why does the left ventricle create a much higher level of pressure than the right ventricle?
Definition
Since resistance is proportional to the length of the vessel the left ventricle must overcome the resistance of the entire arterial system versus the simple pulmonary system.
Term
How do humans pump venous blood and lymphatic fluids?
Definition
Through muscle contraction and one-way valves.
Term
What is the difference in contraction of the right and left ventricles?
Definition
The RV free wall contracts against the intraventricular septum, the LV twists the heart and shortens the ventricle.
Term
Filling of the left ventricle is contributed by both _________ and _________?
Definition
Elongation of the heart and untwisting of the ventricle
Term
List these in order of most to least blood content: capillaries, arteries, veins.
Definition
Veins, arteries, capillaries
Term
Which node functions as a gating system to delay contractions in case of signal irregularities, the SA or AV node?
Definition
The AV node
Term
What is the function of the left and right appendages of the heart?
Definition
They have no active function except as an extra place to distend and collect blood for the atria.
Term
What equation can you use to measure blood pressure?
Definition

BP=Cardiac Output * Resistance

 

(BP = MAP-CVP)

Term
What is the P wave?
Definition
The electrical signal of the SA node firing on the atria.
Term
What segment of the EKG illustrates the brief delay in the electrical impulse passing to the ventricles?
Definition
The PR segment
Term
What is the QRS complex in the EKG?
Definition
The electrical pulse contracting the ventricles.
Term
What is the T wave in an EKG?
Definition
The repolarization wave of epicardium to endocardium in the ventricles; whereas depolarization is from endo to epicardium
Term
What segment of the EKG reveals the atrial repolarization?
Definition
It is hidden from view because it occurs during the QRS ventricle depolarization
Term
True or False: There is an occasional mechanical delay between excitation and contraction.
Definition
False, there is always a delay
Term
Describe what is heard during the two heart sounds S1 and S2.
Definition
S1- AV valves closing, S2- aortic/pulmonic valves closing
Term
What is the ejection fraction (percent of blood) of the RV and LV when they contract?
Definition
50% and 60-65%
Term
What is the difference between the way the RV fills versus the LV?
Definition
RV- passive flow from RA, LV- active aspiration from LA when mitral valve opens.
Term
What is it called when a valve doesn’t close properly causing turbulence?
Definition
Valvular insufficiency/incompetence with regurgitation of flow
Term
What are the 3 phenomena that cause a murmur to occur?
Definition
Stenosis/narrowing of valves causes turbulence; too much flow past a normal valve, like pregnancy or exercise; flow across a normal valve into a dilated artery.
Term
How do you get calcium quickly to the myofilaments in the center of a cell?
Definition
Through calcium channels (L-type) on the surface of the membrane and specifically in T-tubules that are present at every sarcomere in working ventricular myocytes
Term
How do you get enough calcium into the cytoplasm with limited extracellular Ca in T-tubule space?
Definition
Use a small amount of Ca going through L-type Ca channels (10-30%) to trigger large amounts of Ca release in the SR (70-90%).
Term
Where are L-type channels located versus RyR channels?
Definition
L-type are in the myocyte membrane and T-tubule and the RyR are in the SR
Term
How does the SR take up Ca to store it?
Definition
Through a ATP dependent Ca Pump.
Term
Since the SR only takes up 2-4% of myocyte cell volume how does it hold all the calcium it needs?
Definition
Through a molecule called Calsequesterin which bind 47 Ca ions per molecule.
Term
What it Calsequesterin’s role as a calcium channel inhibitor?
Definition
When Calsequesterin is not bound to calcium it binds to RyR/triadin/junction complex inhibiting Ca release; when it is calcium bound it diassociates from the complex
Term
How is graded Ca release accomplished so as to match contractility requirements?
Definition
L-type Ca channels in the T-tubule release Ca to adjacent SR RyR channels in a local fashion to form discrete plaque-like structures called Ca microdomains.
Term
What is the term to describe the random opening of calcium channels in Ca microdomains that is visualized with confocal microscopy?
Definition
Ca sparks
Term
Once released to activate contraction, how is Ca removed to facilitate relaxation in the cell membrane and SR?
Definition
Through a surface membrane Na-Ca antiport exchanger and a ATP dependent Ca pump; the SR uses a SR Ca pump regulated by phospholamban.
Term
True or False: the state of SR filling of Ca is determined by the competition between the SR Ca pump and the Na/Ca exchanger.
Definition
True
Term
When does the Na/Ca exchanger in the myocyte membrane remove Calcium the best?
Definition
When the membrane potential is more negative or when cytoplasmic Na is lower.
Term
What is the role of digitalis in depressing Na/Ca exchange thereby increasing contractility?
Definition
It blocks the Na/K pump, increasing cytoplasmic Na, which slows Na/Ca exchanger, which allows SR Ca pump to take in more Ca, which allows the release of more Ca to contractile units.
Term
How are contractile force and relaxation rate interrelated?
Definition
Through the SR Ca pump since 70-90% of Ca released is pumped back into the SR; increasing SR Ca pump rates enhances relaxation and stores more Ca to release for greater contractility.
Term
Since sympathetic stimulation of the heart releases B-agonists which activate a PKA that phosphorylates targets in the cell, what 3 targets does it have that regulate contraction?
Definition
Ca channels which increase their open probability, Phopholamban which removes its inhibitory effect on SR Ca ATPase, Troponin I which reduces Ca sensitivity of myofilaments to enhance relaxation.
Term
What does parasympathetic activity do due regulate contraction?
Definition
It releases Ach which activates inhibitory G-proteins, reducing cAMP, which limits PKA activity, which induces relaxation.
Term
What goes wrong in heart failure due to chronic B-stimulation?
Definition
Hyperphosphorylation of RyR complexes, causing diassociation of accessory proteins, which increases the Ca sensitivity of RyR; this causes SR Ca leakiness in diastole (arrythmias) and depleting available calcium stores (depressing contractility.
Term
How are B-blockers effective in heart failure?
Definition
They interrupt maladaptive remodeling including downregulation of SR Ca pump and upregulation of Na/Ca exchange which decreases contractility.
Term
What is the equation for cardiac output?
Definition
Stroke volume x HR
Term
What three factors determine the amount of blood ejected per beat, ie stroke volume?
Definition
Preload, afterload, and contractility.
Term
Differentiate preload, afterload, and contractility in regards to stroke volume.
Definition
Preload - the volume in the ventricle at the beginning of contraction which relates to the length of the fiber or radius of ventricle; afterload - the equivalence of force needed to eject blood; contractility - the force with which the ventricle contracts independent of the preload or afterload.
Term
True or False: Since BP measures flow and resistance you can equate that with the stroke volume afterload.
Definition
False, although the BP is a reflection of the afterload it is not the afterload.
Term
What is the law of La Place?
Definition
T~P*r, where T is wall tension, P is pressure inside the chamber, r is the chamber radius
Term
What does compliance refer to in regards to the ventricle?
Definition
The passive distensibility of the ventricle during diastole to stretch during filling, it becomes progressively harder.
Term
What ensures that the voltage signal triggering contraction spreads rapidly from cell to cell?
Definition
Electrical coupling of cells with gap junctions made of connexons
Term
What are connexons made of?
Definition
6 connexin proteins=hemichannel=connexon, 2 connexons=a gap junction channel
Term
What is the main function of cardiac AP upstroke?
Definition
To regulate conduction velocity between cells
Term
Why do purkinje cells lack T-tubules?
Definition
Because their purpose is signal conduction not contraction
Term
Why does the SA & AV node and atrial myocytes lack T-tubules?
Definition
Because ventricular filling depends on suction created by ventricular relaxation (2/3 of filling occurs during first 1/3 of diastole, so atrial kick is surplus)
Term
How do you ensure the current in the AP upstroke is large so that conduction velocity is fast?
Definition
Voltage-dependent Na current.
Term
How would you design current conduction in cardiac cells for regions in which slow conduction is desired?
Definition
No fast Na current like in myocardium and His-Purkinje cells, rely on slow Ca current like in SA and AV nodes
Term
What is the main function of the AP plateau duration in phase 2?
Definition
To regulate contractile force
Term
How is the duration of the AP plateau in phase 2 regulated?
Definition
Slow inactivation of Ca current and activation of time-dependent K currents will modulate the plateau
Term
In phase 2 AP, how do B-agonists prevent AP duration from increasing since they tend to increase Ca current which normally increases AP duration?
Definition
They increase two outward currents of K and Cl which counteract the Ca inward current
Term
During phase 3 AP, how do inward rectifier K channels (which mediate repolarization) assure rapid synchronous repolarization from the plateau back to the resting potential?
Definition
Positive feedback, K current gets larger as membrane potential becomes more negative
Term
In AP phase 4, how do we make a pacemaker to drive the heart, via diastolic depolarization?
Definition
Generate a progressive net inward current during diastole, and by using a voltage clock and a Ca clock to regulate depolarization through multiple currents
Term
How is the heart rate regulated by autonomic tone in phase 4 AP?
Definition
By modifying maximum diastolic potential, diastolic depolarization, and AP threshold.
Term
Where does phase 4 spontaneous diastolic depolarization occur?
Definition
SA nodal, AV nodal and His-Purkinje cells
Term
What percentage of myocyte cell volume does mitochondria occupy?
Definition
30%
Term
What is the function of titin muscle sarcomeres?
Definition
Titin is a long elastic protein that binds the thick filaments to actin and the Z-disk, it is spring like, absorbs most of the diastolic stress/force and is responsible for sarcomere uniformity.
Term
What happens to actin filaments during sarcomere contraction?
Definition
Crossbridges pull actin closer to the myosin A band and the actin filaments slide over each other.
Term
What happens to the rate of myosin cross bridge attachment as the level of intracellular Ca concentration goes up?
Definition
Higher Ca, more cross bridges attach to actin
Term
What is the rate-limiting step in the sarcomere cross bridge cycle?
Definition
The slow release of inorganic phosphate from the myosin head-ADP-Pi complex which makes this complex the majority of the form that you find these components in the cycle
Term
True or False: isometric contraction of myosin cross bridges shows that they exert a maximal force of 10 pN and it moves the unit 10 nm.
Definition
True, so this takes 20-30 cross bridge cycles during systole
Term
True or False: myosin cross bridge attachment to actin monomers creates a negative feedback loop that requires high amounts of calcium to expose more binding site.
Definition
False, cross bridges work through cooperative activation by preventing tropomysoin from block activation sites, this allows other bridges to bind and creats a positive feedback loop.
Term
During resting conditions enough calcium is released during systole to produce _______ percent of maximal force that the heart is capable of.
Definition
30%
Term
What are the two major neurotransmitters, and what system do they work in, either para/sympathetic system?
Definition
Ach works in both, Norepinephrine works in sympathetics; side note - epi works in sympathetics as well
Term
True or False: Ach is the neurotransmitter of all preganglionic neurons and postganglionic parasympathetic neurons.
Definition
True, as well as postganglionic sympathetic nerves at sweat gland and adrenal medulla junctions.
Term
What are the two types of chonliergic receptors and where are they located?
Definition
Nicotinic - in all post-ganglionic cell bodies, cells of adrenal medulla, skeletal muscle cells; muscarinic - all structures innervated by PNS post-ganglionic nerves, sympathetic sweat glands
Term
What two molecules make up Ach and what are the two molecules the result in its breakdown?
Definition
AcetylCoA and Choline, then Choline and Acetate
Term
What are the four steps of Norepinephrine formulation?
Definition
Tyrosine->L-DOPA->Dopamine->Norepinephrine
Term
True or False: NE is the neurotransmitter for all post-ganglionic sympathetic neurons, except sweat glands
Definition
True
Term
True or False: Adrenergic stimulation leads to increased rate, contractility, and conduction velocity.
Definition
True
Term
True or False: the heart has an intrinsic rate of 50 bpm and is modulated by vagal tone to have a higher rate.
Definition
False, the rate is 100, but is modulated to keep it lower.
Term
What is the response of phase 4 spontaneous depolarization sinus rhythyms to PNS and SNS stimulation?
Definition
PNS reduces rate of depolarization and increases time to threshold, SNS does opposite
Term
Which, PNS or SNS, innervate the bronchial vasculature and the bronchial smooth muscle?
Definition
The SNS affects the vasculature, PNS innervates smooth muscle causing bronchoconstriction (but SNS releases EPI which causes bronchodilation)
Term
Of the two groups of leads on an ECG, which goes on the limbs and which goes on the chest - Columns I/II/III/aVR/aVL/aVF and Columns V1-6?
Definition
First groups on limbs, second of chest
Term
What happens during P wave, QRS wave, and T wave?
Definition
Atrial depolarization and contraction, ventricular contraction, ventricular repolarization
Term
How do you determine heart rate on an ECG?
Definition
Find a QRS complex that falls on a heavy line, start counting at the next heavy line like this 300, 150, 100, 75, 60, 50, 43
Term
How do you determine heart rhythym of an ECG and what leads do you look at?
Definition
Look at lead II and V1, then identify P waves, QRS waves, and HR.
Term
How do you determine axis on an ECG?
Definition
Look at two leads, I and aVF, then since the heart is depolarized from the top to bottom and right to left this should lead to a positive deflection in both spots.
Term
In an ECG what are the 4 possible axis determinations in order of most to least common?
Definition
The first is normal with positive deflection in both lead I and AVF, the second is LAD with I being positive and AVF being negative, the third is RAD with I being negative and AVF positive, and the fourth is RAD extreme where both are positive.
Term
What is the PR interval in an ECG measure and what is normal?
Definition
The length of time for signal delay from SA node to AV node, normal being .12-.22
Term
How do heart muscle cells increase force development without changing sarcomere length?
Definition
Sympathetic stimulation will phosphorylate L-type Ca channels, increasing their conductance, loading the SR with more Ca, and causing more Ca release.
Term
If blood pressure acutely rises by 40 mmHg, what would happen to left ventricular chamber size and what will happen to the wall stress as a consequence?
Definition
Size would increase, LV contractile stress would increase Increased afterload will decrease the stroke volume and thereby increase end systolic size. When the chamber refills for the next beat, its end diastolic volume will be greater than before, causing increased wall stress.
Term
Understand the following cross bridge cycle.
Definition
[image]
Term
Understand how the length of the sarcomere relates to the stress level in the following image.
Definition
[image]
Term
Understand the following which leads to use and what the deflections define as far as axis determination.
Definition
[image]
Term
The parasympathetic nervous system is also called the "cranialsacral outflow." Which cranial nerves give rise to parasympathetic, preganglionic neurons?
Definition
CN III, VII, IX, X
(CN 3,7,9,10 for the Roman numeral-impaired)
Plus the sacrum
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