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CVPR > CV Test 1 > Flashcards

CV Test 1 Flashcards

1
Q

Phase 0 of Fast Action Potential

A

Rapid upstroke due to Na entry into the cell

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2
Q

Phase 1 of Fast Action Potential

A

Partial repolarization to OmV

Due to inactivation of Na channels and activation of IKTO to have K efflux

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3
Q

What channel is responsible for Phase 1 of Fast AP?

A

IKto channel; Kv.4.3 tetramer with Khip2 - voltage dependent activation and inactivation

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4
Q

Phase 2 of Fast AP

A

Prolonged Plateau phase. Balance between Outward Potassium flow (IKR and IKS) through delayed rectifier channel and inward Calcium flow though LTCC.

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5
Q

Delayed Rectified K channels

A

delayed in activation and are responsible for the plateau phase of Fast AP and the rapid repolarization of Phase 3

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6
Q

Phase 3 of Fast AP

A

Rapid hyperpolarization due to inactivation of Ca Channel and increasing activation of IKR and IKS

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7
Q

Phase 4 of Fast AP

A

Absolute refractory period. Deactivation of IKR and IKS, activation of inward rectifier IKI to keep near Ek.

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8
Q

Channel more active in Phase 4 of Fast AP

A

IKI (inward rectifier K )

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9
Q

Where are slow Cardiac Action Potentials located?

A

SA and AV nodes

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10
Q

What are the major channels differences between slow and fast AP producing cells?

A

Reduced expression if INa and IKI chennels; increased expression of IF and ICaT.

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11
Q

Phase 0 of slow AP

A

slow upstroke due to activation of ICaT and ICaL. NO activation of Na channels

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12
Q

Phase 1 of slow AP

A

does not exist!

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13
Q

Phase 2 of slow AP

A

does not exist

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14
Q

Phase 3 of slow AP

A

Repolarization - balance between Ca and delayed rectifier current IKR and IKS.

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15
Q

Phase 4 of slow AP

A

Pacemaker Potential due to hyperpolarized triggered IF (cation fluxes to drive slow depolarization to -30mV).

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16
Q

Na Channel

A

Nav1.5 - voltage dependent actiation and inactivation

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17
Q

Calcium Channels

A

L type and T Type

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18
Q

DHPR

A

L type Ca Channel; Cav1.2 and Cav1.3 that are high voltage activated, and voltage and [Ca} deactivated.

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19
Q

T type Ca Channels

A

Cav 3.1 and 3.2; Low voltage activated and voltage deactivated; only present in nodal cells

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20
Q

Potassium channels

A

IKto, Delayed Rectifier (IKR and IKS), Inward rectifiers - IKi and GIRK

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21
Q

IKto

A

Kv4.3 tetramer with KCHIP2, voltage dep act and inactivation; only in fast AP to cause brief hyperpolarization

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22
Q

IKr and IKs

A

delayed rectifier K channels. HERG (IKr) and KvLQT (IKs)

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23
Q

IF channel

A

Time dependent Cation channel in pacemaker cells that are Na and K permeable; activated with hyperpolarization.

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24
Q

IK1

A

Kir tetramer - inward rectifier channel, inward K whens lighly above Ek

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25
Q

GIRK

A

IKACh, activated by muscarinic recpetors, slows pacemaking

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26
Q

What does the R phase correspond to in the channel cycle?

A

Phase 0 - opening of Na Channels

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27
Q

What does ST phase correspond to in the channel cycle?

A

Phase 2

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28
Q

What does T phase correspond to in the channel cycle?

A

phase 3

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29
Q

P wave

A

atrial depolarization/contraction 0.08-.1 seconds

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30
Q

QRS wave

A

vent. contraction 0.06-0.10

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31
Q

T wave

A

Vent. relaxation

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32
Q

PR interval

A

Conduction time across AV node 0.12-0.2 sec

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33
Q

QT interval

A

Total depol and repol of ventricle times less than 0.44 sec

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34
Q

Path of depolarization of ventricles

A

1) in upper septum, left to right ventricle
2) down septum to apex
3) depolarization from endocardium to epicardium
4) apex upward
5) ends at base of ventricles

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35
Q

Repolarization of ventricles

A

in opposite direction becuase endocardium depolarizes before epicardium, but epicardium repolarizes before endocardium.

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36
Q

what causes first degree AV node block?

A

transiet reversible influence or structural defect; heightened vagal tone, transient AV node ischemia, drugs that depress conduction of AV node, MI degeneration

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37
Q

what causes a second degree AV node block?

A

Intermittent failure of AV node - also transient, acute MI in AV node region; Type II: is due to conduction block beyond AV node in bundle of his or purkinje.

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38
Q

What causes third degree AV node block?

A

acute MI and chronic degeneration that causes separation between conduction of atria and ventricles

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39
Q

Sympathetic regulation of Inotropy

A

NE binds to Beta-Andrenergic receptors to activate GalphaS to target AD and increase cAMP and PKA activation..

1) DHPR
2) RyR
3) Tn-I
4) Phospholamban (PLB)

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40
Q

Phosphorylation of DHPR

A

by PKA to increase inotropy… the effect is slowed deactivation to increase calcium entry and increase Calcium induced calcium release.

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41
Q

Phosphorylation of RyR

A

Increases sensitivity to calcium and increases calcium release to increase inotropy and chronotropy

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42
Q

Phosphorylation of Tn-I

A

Phosphorylation of Tn-I by PKA decreases Tn-C’s sensitivityt to calcium to cause faster dissociation and increase lusitropy. Does not effect inotropy.

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43
Q

Phosphorylation of PLB

A

relieves the inhibition on SERCA, so that SR uptakes Ca faster. Increase Inotropy and lusitropy.

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44
Q

what controls HR at rest?

A

both parasympathetic and sympathetic neuronal control

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45
Q

Sympathetic control of chronotropy

A

Ne acts on B-adrenergic receptor to active G alpha S to activate AC and increase cAMP and PKA.
cAMP –> 1) binds to Hyperpolarization Activated cyclic nucleotide channels, pKA phosphorylates 1) DHPR 2) RyR, both of which increase activity of NCX

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46
Q

cAMP binding to HCN

A

causes increased depolarization (If - inward movement of Na and K) and increase excitability to lead to more APs

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47
Q

parasympathetic control of Chronotropy

A

ACh binds to M2 repetor to activate G alpha I to inhibit AC, cAMP, and PKA. So these all promote hyperpolarization. The primary method is break away of Beta-gamma to activate GIRK channels (outward flow of K) to stabalize near Ek and decrease excitability.

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48
Q

Sympathetic Control of Vasculature

A

NE from the sympathetic neuron acts on alpha - AR to activate Gq to activates Phospholipase C and IP3. IP3 causes activation of IP3R on SR and increased Calcium release. This causes vasoconstriction.

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49
Q

Baroreceptors

A

Sense stretch in the aortic arch and carotid sinus. when stretched, activate eNaC channels that cause inward movement of Na to generate an action potential via the IX and X nerves to act on the cardiovascular control center in the medulla. This center regulates HR and Vasodilation levels.

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50
Q

What controls vasodilation

A

not necessary parasympathetic response, but less sympathetic activation.

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51
Q

bainbridge response

A

low pressure in atria and vena cava trigger baroreceptors to mediate increase in Heart rate

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52
Q

Vasoactive Metabolites in vasocontrol

A

local feedback to control vasodilation and constriction. Triggered by PO2, PCO2, pH, extracellular K, adenosine.

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53
Q

why does extracellular K act as a metabolite

A

ATPase can’t keep up and indicates lots of activity and vasodilation

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54
Q

adenosine

A

acts on A2 purogenic receptor on VSMC to activate Galpha S to increase cAMP. cAMP inhibits MLCkinase to cause vasodilation. It also activates Protein Kinase to hyperpolraize cell by activating K ATPase channels.
In cardiac cells, it binds to A1 Receptors that are tied to Gi, proteins to decrease cAMP and hyperpolarize the cell to decrease HR.

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55
Q

Myogenic Response

A

Stretch causes activation of Trp Channels in Vascular Smooth muscle cells that leads to non-selective depolarization and Ca entry. This maintains flow despite changes in pressure via vasoconstriction

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56
Q

NO synthesis

A

ACh or Bradykinin bind to surface of endothelial cell to activate IP3 and trigger Ca release. Calcium activates calmodulin to activate NO synthetase to convert Arginine into NO. NO diffuses across membrane into smooth muscle cell to activate gunaylyl cyclase to increase cGMP to activate PKG to activate SERCA and inhibit L type Ca Channels. Both decrease cytosolic Ca and lead to vasodilation and ultiatmly decreased Major Light Chain Kinase activity.

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57
Q

Endothelin

A

in the Endothelial cell, Big Endothelin is converted to active ET-1 by ECE in membrane. ET-1 binds to ETR on SMC membrane and activate Gq to actiate IP3 and Ca release. Increase calcium causes increase contraction and vasoconstriction

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58
Q

Control mechanism for endothelin

A

ET-1 binds to ETR receptor on endothelial cell to act on NO synthase enzyme to promote production of NO - vasodilator

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59
Q

what triggers Renin release

A

sympathetic stimulation, hypotension, decrease Na delivery (kidney secretes its)

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60
Q

Effects of Angiotensin II

A

Cardiac and Vasculature hypertrophy
Systemic vasoconstriction
increased thirst
stimulate adrenal cortex to increase aldosterone release
stimulate pituitary to release anit-diuretic hormone/vasopressin

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61
Q

Aldosterone

A

hormone released from adrenal cortex in response to AnII to cause Na and Fluid retention.

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62
Q

ADH

A

Anti-diuretic Hormone or Vasopressin released from pituitary with AnII to cause Na and Fluid retention, as well as vasoconstriction

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63
Q

ANP

A

Atrial Natiruetic Peptide is a vasodilator that is released due to atrial stretch

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64
Q

effects of ANP

A 
decreases renin release to decrease vasopressin and aldosterone release. 
drecreases endothelin release
decreases vascular resistance
Increase fluid egress
Increase natiuresis
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65
Q

ANP action

A

ANP bind to NPrecpetor to active gunylate cyclase direction (Not GPCR) to increase cGMP and activate SERCA and Na and H20 excretion.

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66
Q

Forward Heart Failure

A

inability for CO to meet metabolic demands of the body, due to low Cardiac output

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67
Q

Backward heart Failure

A

filling pressures are abnormally high to meet demands of the body, increased congestion.

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68
Q

what fails in HF?

A

1) displacement pumps (systole and diastole)
2) L or R side
3) coordinated electrical system
4) Valves: regurgitation or stenosis (resistance)
5) Coronary Dysfunction (regurg or stenosis)
6) Pericardium

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69
Q

What contributes to SV?

A

Increased inotropy and preload and decreased afterload

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70
Q

systolic HF

A

Loss of contractility due to weak or damaged myocardium. Decreased inotropy to cause increase ESP and decreased SV.

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71
Q

examples of systolic HF

A

Decreased ejection fractio (HFrEF, LV systolic dysfunction); Ventricular enlargement (dilated cardiomyopathy).

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72
Q

Systolic HF is due to..

A

direct destruction of Heart muscle cells via MI or other cuases

2) Overstressed Heart muscle - meth, cocaine
3) Volume Overload - mitral regurgitation

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73
Q

Diastolic HF

A

Stiff or non-compliant heart due that decreases pre-load and lusitropy. Requires increased pressure to achieve same filling volume and ultimately increases ESP

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74
Q

Diastolic HF samples

A

Normal ejection fraction : HFpEF, preserved systolic function
LV hypertrophy

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75
Q

Diastolic HF is due to..

A

Increaesed afterload - hypertension, aortic stenosis, dialysis
Myocardial fibrosis - hypertrophic cardiomyopathy
External compression - pericardial fibrosis, effusion

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76
Q

Right sided HF is due to..

A

Left sided HF
Lung disease or pulmonary Hypertension, “cor pulmonale”
RV overload - due to shunt, tricuspid regurgitation
RV myocardium damage

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77
Q

Neurohormonal action in heart failure

A

the short term solution to increase EDV pressure to preserve the SV. Sensed by Juxtaglomeruluar reflex for AAR system and baroreceptors to increase adregneric activation.

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78
Q

Physiological Hyptertrophy

A

During pregnancy and chronic exercise. Myocyte length> myocyte width with no fibrosis. General increase in chamber size and no dysfunction.

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79
Q

What leads to cardiac dilation?

A

MI, Dilated cardiomyopathy, pregressio from pathological hypertrophy.

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80
Q

Cardiac Dilation

A

increase in chamber size via myocyte loss via apoptosis. Due to increase in NE and AII, and mechanical strain. Myocyte length is greater than myocyte width with excessive fibrosis and cardiac dysfunction.

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81
Q

What causes pathological hypertrophy

A

chronic hypertension and aortic stenosis

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82
Q

Pathological hypertrophy

A

no change in chamber size, but increased wall stress due to deposition of ECM to maintain CO in an attempt to decrease stress. Myocyte width is greater than length. Some fibrosis and some cardiac dysfunction.

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83
Q

alpha myosin

A

high ATPase acitivity, more effective at contraction

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84
Q

beta myosin

A

low ATPase activity, less effectie at contraction. In HF shift to Beta myosin

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85
Q

Changes in calcium regulation in HF

A

increase Ltype Ca Channel and decrease in SERCA function (increased PLB), to cause increased cyto Calcium levels and decrease lusitropy.

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86
Q

Changes in gene expression in HF

A

early acute: PKA and PKC activation

chronic: PKE, PKD, CAMK (calcineurin)

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87
Q

Calcineurin

A

A Ca dependent phosphatase that remove Phosphate from NFAT to dead to cardiac remodeling

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88
Q

Smooth vs. Striated Muscle

A

VSMC is mononucleated, with gap junction and no sarcomere. It does not require the SR to release Ca to contract. has similar SERCA reuptake system, but delivers slower and sustained cotnraction. Contraction is dependent on phsophroylation of Myosin Head (not directly Ca dependent)

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89
Q

VSMC activation

A

1) Ca entry into cyto from SR and Ca Channel
2) Ca binds to calmodulin
3) Ca-CaM bind ot myoslin light chain kinase to activate
4) Myosin Light Chain kinase phosphorylates light myosin head to facilitate cross bridge
5) myosin-light chain phosphatase dephosphorylates myosin to inactivate.

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90
Q

PKA in cardiac vs VSCM?

A

PKA promotes contraction via phosphroylation of Ca entry into cyto (cardiac cells)
IN VSMC pKA regulates phosphorylation of MLCK to influence contraction.

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91
Q

Class I Anti-arrhythmics

A

Na Channel blockers that mostly affect fast response cell. Decrease conduction velocity and increases effective refractory period. Use Dependent.

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92
Q

Class Ia

A

Quinidine, procainamide, dispyramide
Blocks Na Channes - slow upstroke
Delays repolarization by blocks K channels (class III action).
Together these prolong refractory period by prolonging depolarization.

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93
Q

Decreasing conduction velocity - class I

A

converts unidirection block into bidirectinla block - so signal cant propagate into a depressed region.

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94
Q

Two conditions necessary for re-entry

A

1) unidirectional block 2) conduction time > refractory

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95
Q

How to terminate re-entry?

A

1) convert unidirection block to bidirectional block 2) prolong refractory period

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96
Q

Use Dependent

A

drug that selectively targets overactive cells (channels open) and stabilize the cell in the inactive state to prolong the refractory period.

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97
Q

Quinidine

A

First antiarrhythmic drug - Class Ia
In addition to Na block; Blocks K channels to prolong AP
Anti Cholinergic (vagal inhibitor)
Alpha-Adrenergic antagonists

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98
Q

Class IB

A

Lidocaine, Mexiletine, Phenytoin
Mild slowed upstroke due to Na block,
decreased duration of action potential (decreased plateau phase - shortened repolarization)
prolonged refractory - use dependent.
Purely Class I effect - Lidocaine is least toxic.

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99
Q

Class IC

A 
Propafenone, Flecainide, Encainide
Markedly slow upstroke
prolonged phase 2
delayed repolarization due to K channel block
Highly pro-arrhythmic.
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100
Q

so of the Class I drugs, which on has the slowest upstroke?

A

C>A>B

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101
Q

which Class I shows delayed repolarization

A

A > C, B is shortened repolarization

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102
Q

Class I drugs - which ones have extended refractory period?

A

all - all are use dependent.

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103
Q

Class II anti-Arrhythmic

A

Beta blockers - to reduce If, LTC current, and K current.
Reduced upstroke, slow repolarization at AV node, Decreased Phase 4 slope to prolong refractory period.
Specifically reduces pacing rate.
Used at AV nodal re-entry and controlling A fib.

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104
Q

Class II examples

A

Propanolol, Metorpolol, Esmolol

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105
Q

Class III

A

K channel blockers - block Rapid K channels to prolong Phase 2.
Prolongs refractory period because long phase 2 causes increased Na channel inactivation and leads to decreased re-entry.
NOT use dependent.

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106
Q

Examples of Class III

A

Ibutilide, Dofetilide, Amiodarone, Sotalol, Bretylium

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107
Q

Amiodarone

A

Class III, but with class I effect at reducing conduction velocity by decreasing phase 4 slope.
Side effects: bradycardia, heart block, corneal depoits, hypo/hyperthyroidism, pulmonary fibrosis
T1/2 13-100 days.

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108
Q

Sotolol

A

Class III, but also acts as beta blocker

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109
Q

Class IV

A

Calcium Channel blockers
Use Dependent of L type Ca Channel located primarily in nodal cells.
Slow upstroke to slow conduction velocity.
Prolongs refractory period.
Side effect: hypotension

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110
Q

Class IV examples

A

Verapamil

Diltiazen

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111
Q

Adenosine

A

Binds to A1 receptor to increase K current and decrease LTCC and IF. To cause decreased SA and AV firing rate and reduced conduction at AV node.
Resembles Beta Blockers (both reduced cAMP).
Short half life of 10 seconds.
Causes flushing chest burning, SOB

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112
Q

What cell types are in the heart

A

Endothelial cells>cardiac fibroblasts>mycocytes

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113
Q

Cardiac fibroblasts

A

mediate ECM of heart, lay down foundation upon which myocytes function

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114
Q

ECM in heart it made up of..

A

fibrillar collagen type I and III

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115
Q

Cardiac vs. skeletal muscle

A

1) both striated
2) not under direct neural control - autonomic
3) shorter, narrower, richer in to mitochondria, mononucleated
4) slower ATPase than skeltal muscle (faster than smooth)
5) Thin filament regulated (Ca binding to troponin regultes actin-myosin interaction

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116
Q

Intercalated Discs

A

connect cardiac muscle cells, coincide with Z discs and contain desmosones and gap junctions.

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117
Q

Desmosomes -

A

adhesion and assures force generated in one cell is transfered to the other, connects to ECM

118
Q

what makes up the maorjity of the heart cell volume?

A

myofibril and mitochondria. The rest is sarc, T tubule, SR, intercalated disks, gap junctions

119
Q

Myocyte

A

single muscle cell containing the usually orgnaless plus many myofibrils

120
Q

Myofibril

A

end to end array of idential sarcomeres

121
Q

Sarcomere

A

unit of contractile activity - composed of actin and mysoin and estends from Z line to Z line.

122
Q

does tropomysin and troponin interact with actin or myosin?

A

actin

123
Q

Troponin C

A

dumbell shaped; N lobe with ONE Ca binding site.

124
Q

Troponin I

A

N terminal extension of 32 amino acids that contain PKA phosphoryltion site for adregnergic responsiveness. Interacts with TN-C but is released with phosphorylation.

125
Q

Troponin T

A

binds to tropomysin. N terminal regulated with Calcium sensitivity.

126
Q

Tropomysin

A

alpha form in heart; lies over myosin binding sites.

127
Q

Relaxation cycle on contraction - molecular mechanism

A

1) AP leads to Ca release
2) Ca bind to Troponin C
3) Troponin undergoes structure change to move tropomysin out the way
4) myosin binds to actin and crossbridge moves
5) calcium is released, tropomysin reblocks binding sites - relaxation.

128
Q

Diastole - Actin Myosin Relationship

A

1) Resting state: No Ca, non force generating

2) Transition state: Ca bound, non force generating

129
Q

Systole Actin Myosin relationship

A

3) Active State: Ca bound force generating

4) Active state: No Ca bound, force generating

130
Q

Titin

A

giant protein that functions as an elastic spring that extends form the M line to the Z line to prevent over stretching. Responsible for muscle tension at rest.

131
Q

Titin Isoforms

A

N2B and N2Ba

132
Q

N2B

A

titin isoform that is stiff

133
Q

N2Ba

A

titin isoform that is not very stiff

134
Q

length tension relationship

A

increasing muscle length increases muscle tension

135
Q

Mechanisms behind the Length Tension Relationship

A

1) extent of overlap
2) change in calcium sensitivity
3) increased calcium release

136
Q

How does extent of overlap affect length tension relationship

A

peak tension develops at lengths of 2.3 an 2.2 uM. This indicates that muscles are a prime length for tension development.

137
Q

How does changing calcium sensitivity affect length tension relationship?

A

a short lengths - only a portion of potential cross bridges can be activated. At longer lengths, more cross-bridges become activated and there is no time delay.

138
Q

How does increased calcium release affect the length tension relationship?

A

occurs several minutes after changing muscle length - due to stretch sensitive channels in cell membrane.

139
Q

What factors regulate calcium sensitivity of the myofilament?

A

TnI phosphorylation
TnT Isoform composition
Sarcomere length

140
Q

TnT Isoform and Calcium sensitivity

A

N-terminal extension of TnT decreases sensitivity to calcium

141
Q

PKA phosphorylation of TnI and calcium sensitivity

A

Phosphorylation decreases Ca sensitivity to TnC, to promote lusitropy.

142
Q

Force Velocity Relationship

A

increasing preload enables muscle to contract faster against a given afterload

143
Q

what change velocity at sarcomere level?

A

Phosphorylation of MLC

Phosphorylation of MyBPC

144
Q

Ventricle Geometry and Muscle Fibers

A

Increase in ventricular volume causes increased ventricular circumference and increase in length of individual muscle cells.
2) Increase in tension on individual cell sin wall –> increases intraventricular pressure.
3) as ventricular volume increases, a greater force is require from each muscle cell to produce a given intraventricular pressure.
La of Laplace: Wall stress equals tranmural pressure X radius of chamber/wall thickness.
To compensate for increase in pressure, wall thickness increases.

145
Q

Concentric Vs Eccentric hypertrophy

A

Concentric - increase n muscle width - pathological hypertrophy
Eccentric: increase in muscle length - dilation

146
Q

Working Myocytes

A

in atria and ventricles that are quire large -20 um in diameter

147
Q

Nodal myocytes

A

in SA and AV nodes and are smaller, specialized for electrical conduction instead of contraction.

148
Q

What supplies Right atrium and Right ventricle with blood?

A

Right Main coronary Artery

149
Q

Left main coronary Artery supplies..

A

left atrium and ventricle with blood and bifurcates into left anterior descending (LAD) and circumflex.

150
Q

Aorta - Types of Vessel

A

Large single outflow form heart with elastic and smooth muscle fibers in wall to dampen pulsatile flow. 2mm thickness 12 mm radius

151
Q

Arteries - type of vessel

A

Thick walled (1mm) and resistnat to expansion.
Diameter 4 mm
Distribute blood to organs

152
Q

Arterioles - type of vessel

A

Relatively thick wall with lots of VSMC (20um);
diameter 15 um
highly innervated - primary site of regulation of vascular resistance.

153
Q

Thickness of arteries.

A

Arterioles>Artery>aorta.

154
Q

Venules and Veins type of Blood Vessles

A

Thin walls of similar diameters of arteries.
Capacitance vessels that hold most of the blood volume.
Low pressure - one-way valves

155
Q

Vena Cavae

A

Large diameter 50 mm with very thin walls 1.5 mm, very low pressure.

156
Q

Tunica Adventitia

A

outermost layer of vessel that contains connective tissue like collagen and elastin

157
Q

Tunica Media

A

mIddle layer of vessel that innervated smooth muscle cells. Controls vessel diameter

158
Q

Tunic Intima

A

Inner layer with connective tissue and vascular endothelium.
Important site of signaling
Site of plaque formation.

159
Q

Pre-Capillary sphincters

A

smooth muscle bands at junction of arterioles and capillaries to regulate blood flow through capillary beds

160
Q

lymphatic system

A

Lymph is filtered interstitial fluid that is filter and is run through the lymphatic system which is low pressure with one-way valves.

161
Q

What promotes flow of lymph?

A

increased interstitial pressure, smooth muscle contraction of lymph vessels, contraction of surrounding skeletal muscles

162
Q

overdrive suppression

A

when SA node is overtaken by an ectopic pacemaker to trigger contraction independently.

163
Q

AV node

A

located a right side of heart near opening of coronary sinus to regulate action potential propagation through ventricles.

164
Q

How does signal spread from AV node”?

A

through conducting pathways that propagate to L and right ventricles that are larger in diameter and able to spread the signal rapidly.

165
Q

what prevents the depolarization from spreading from atria to ventricles, besides AV node?

A

CT electrical insulation

166
Q

Ena

A

+58

167
Q

NCa

A

+124

168
Q

Ek

A

-90

169
Q

T-Tubule Lumen Ca Concentration

A

less than 2 mM

170
Q

Calcium regulation/cycle

A

1) Ca enters via DHPR and activates RyR to cause larger flux of Ca from SR.
2) Ca activates contraction by binding to troponin
3) Ca is removed from cytoplasm by SERCA pump on longitudinal SR (2 Ca per cycle) where it diffuses to bind to calsequestrin at terminal cisternae.
4) Ca is also removed by NCX at junctional domain and via PMCA transporters.

171
Q

Calsequestrin

A

binds to Ca in terminal SR with low affinity and high capacity. Low binding affinity, but high storage capacity of calcium.

172
Q

why isn’t calcium entry from DHPR sufficient for contraction?

A

Filaments located far away from DHPR channel would see Ca signal later than those closer –> non-synchronous contraction.
While SR is wrapped extensively and Ca never needs to move far.

173
Q

CaV1.2

A

DHPR - L Type Ca Channel.

Four homologous repeat subunits. Binds to Beta, and alpha2delta subunit.

174
Q

RyR

A

enormous homo-tetramer in SR that binds to ryanidine with high affinity. From different physiological pathway than DHPR

175
Q

Cardiac vs Skeletal muscle calcium

A

ECC coupling requires external Ca to trigger Ca release form RyR in heart.
Skeletal muscle does not require Ca entry for Ca to be released from RyR.
Both used Ca to bind to troponin to activate contraction.

176
Q

Cav1.2 2-3 loops

A

can be replaced with Cav1.1 loop to couple cardiac to skeletal type contraction.

177
Q

Why is SERCA most important in cardiac cytoplasmic Ca removal?

A

Voltage against SR is kept at 0mV so it is easier to transport vs. the cell surface membrane at -70mV.. So it is not as must work.

178
Q

NCX

A

3 Na in for 2 Calcium out; net effect is that it depolarizes the membrane.
Can switch direction based on membrane potentials and concentrations.

179
Q

Cardiac Glyocisides

A

former Tx for heart failure - blocks Na/K pump that extablishes the Na concentration gradient. Thus Na will build up in cell and NCX is no longer able to function and lots of Ca is stuck in cytosol..

180
Q

Consequences of over NCX use?

A

depolarization triggers abnormal diastolic SR Ca release to trigger delayed afterpolarizations and gives rise to arrhythmias

181
Q

Norepinephrine

A

Released by sympathetic nerves to
1) Increase HR (chronotropy) by raising firing rate at SA node.
2) increase inotropy (contractile force)
3) increase relaxation rate (lusitropy)
2-3 are due to B-adrenergic receptors to activate PKA.

182
Q

Result of Phosphorylation of DHPR

A

increased inotropy - contractile force

183
Q

Result of Phosphorylation of RyR

A

increase inotropy

184
Q

Result of PLB phosphoryaltion

A

increase inotropy and lusitropy

185
Q

Phosphorylation of Tn-I

A

Increase lusitropy

186
Q

why are genetic disorders of EC coupling difficult to study?

A

requires model systems which are difficult because:

1) Splicing/associated proteins may be different in reference cells
2) transgenic/knockout/in mice are different from humans (faster HR)
3) disease manifestations take many years to develop

187
Q

Timothy Syndrome

A

Cardiac Arrhythmias due to de Novo mutations in CaV1.2 (multisystem) to block voltage inactivation to PROLONG QT interval and polymorphic ventricular tachycardia.
TS: G406R Exon 8A
TS: G406R and G402S - Exon 8

188
Q

Timothy syndrome symptomes

A

syncope, arrhythmia, sudden death, intermittent hypoglycemia, immune deficiency, cognitive abnormalities - autism

189
Q

Brugada Syndrome

A

Sudden unexplained death syndrome
Mutations in Nav1.5 KChip2 (IKTO) and other proteins including ankyrin.
Subset iwth mutations in Cav1.2, B2B accessory of DHPR>

190
Q

Brugada mutation - Cav1.2 and B2B mutation EKG

A

Shortened QT interval

191
Q

Catecholaminergic Polymorphic ventricular Tachycardia

A

No ECG abnormalities at rest, but ab. with exercise of catecholamines.
Mutations in RyR, Ressesive mutaions in calsequestrin (dramatic loss of lumenal Ca buffer and ineffectie regulation of RyR).
Causes B-AR in release of Ca not triggered by DHPR during plateau or shortly after repolarization –> arrhythmias

192
Q

CPVT - Treatment

A

Beta Blockers

For some patients, need to prevent release of RyR with Tetracaine OR block Na channels like Flecainide

193
Q

Function of ANS

A

maintain homeostasis within a narrow physiological range amid changing external conditions.

194
Q

ANS vs SMS

A

ANS: involuntary, diffuse, slow AP, innervates smooth, cardiac and gland muscles, disynaptic
Somatic: voluntary, specific projections, rapid, innervates skeletal muscle, monosynpatic

195
Q

what does disynpatic mean for ANS?

A

preganglionic nuerons located in brainstem or spinal cord connect to post-ganglionic neurons in ganglia outisde CNS. PostG neurons project to smooth muscle, cardiac cells or glands.

196
Q

Solitary Tract

A

located in the medulla - contains nucleus of ANS neurons that convey visceral sensory input

197
Q

Hypothalamus

A

in forebrain, conveys internal goals and states.

198
Q

Myelination of pre and post ganglionic neurons

A

Pre are myelinated, post are nonmyelinated

199
Q

Sympathetic NS - where do nerves originate compared to parasympathetic

A

S: thoracic and lumbar spinal cord
P: brainstem and sacral spinal cord

200
Q

Where are the ganglia located in sympathetic vs parasympathetic?

A

S: near spinal cord in sympathetic chain
P: near target organs

201
Q

Ratio of Pre to post ganglionic neurons in sympathetic vs. parasympathetic

A

Sympathetic have many more post ganglion than pre 10:1

Parasympathetic have more post than pre as well, but only 3:1

202
Q

White ramus

A

sympathetic nerves exit the spinal cord via the ventral roots and pass through this myelinated section before entering the sympathetic trunk.

203
Q

How do parasympathetic pre-ganglionic nerves reach their ganglion?

A

In the brainstem they exit the via cranial nerve III (oculomotor), VII (facial), IX (glossopharyngeal), an X (Vagus).

204
Q

PreGanglionic NT for Symp and Para

A

ACh

205
Q

PostG NT for Sym and Para

A

Sym: Norepinephrine
Para: ACh

206
Q

Gray Ramus

A

exit out of sympathetic trunk with unmyelinated post-ganglionic fibers that project to sweat glands, blood vessels, viscera etc.

207
Q

Are ACh receptor inotrophic?

A

Yes! Nicotinic receptors are

208
Q

Type of ACh receptors?

A

Nicotinic *ionotropic) and muscarinic

209
Q

Nicotinic

A

an ionotropic ACh receptor on Post G neurons.

Ligand gated, nonselective ion channel to allow movement of Na and K into cell for depolarization and excitation.

210
Q

Muscarinic Receptor

A

a ACh that is present on effector cells of cardiac muscle, smooth muscle and glands.
a GPCR that either stimulates or inhibits intracellular effectors

211
Q

NE receptors

A

Alpha or Beta adrenergic

212
Q

Alpha 1 Receptor

A

responsible ror vasoconstriction of skin

Gq acts on PLC –> IP3 and DAg

213
Q

Agonist for A1

A

phenylephrine

214
Q

Antagonist for A1

A

doxazosin

215
Q

Alpha 2 Receptor

A

presynaptic inhibition of NE release to cause mixed effects.

Acts via Gi to inactive adenylate cyclase

216
Q

A2 agonist

A

Clonidine

217
Q

A2 antagonist

A

Trazodone

218
Q

B1 Receptor

A

increases HR by activating Gs to activate cAMP

219
Q

B1 Receptor agonist

A

dobutamine

220
Q

B1 Receptor antagonist

A

Atenolol

221
Q

B2 Receptor

A

increased HR and vasodilation in skeletal muscle, smooth muscle relaxation.
Gs

222
Q

B2 agonist

A

albuterol

223
Q

B2 Antagonist

A

Butaxamine

224
Q

Adrenal Medulla

A

a sympathetic ganglion that is innervated by pre-ganglionic neurons (superficial to kidney)
releases NE and E to lead to hormone like effects of widespread sympathomimetic.

225
Q

Sympathomimetic

A

mimics activation of sympatheic NS

226
Q

Sympathetic stimulation of HR

A

1) Action potential to SA node causes NE binding to Beta-1 Receptor
2) activate GPCR with G to active AC
3) AC activates PKA
4) PKA activates Ca channels to increase depolarization and amplitude
5) cAMP acts on HCN to cause increased repolarization back to baseline and decrease time between AP to increase HR and

227
Q

Parasympathetic control of HR

A

ACh bind to M2 receptor
2) acivates G protein i to inhibit adneylyl cyclase.
3) decrease in cAMP
4) active BY activates GIRK to cause hyperpolarization.
Shallower slope and decreased amplitude.

228
Q

sympathomimetic Drugs

A

mimic sympathetic activity by activating sympathetic or inhibiting parap
Atropine

229
Q

Parasympathomimetic drug

A

mimic para by activating para or inhibit sympth

Propranolol

230
Q

Barorceptor function

A

sense stretch in aortic arch and carotid sinus and send info via vagus nerve to nucleus solitary tract (NTS) in medulla. This reugulates level of sympathetic and parasymathetic output.

231
Q

High BP and baroreceptor

A

1) Increase in BP triggers excitatory neuron release of glutamate. Glutamate acts on parasympathetic neurons to facilitate ACh release on SA node to decrease force of contraction and BP.
2) Glutamaneric neurons also release GAGA, an inhibitor NT that binds to sympathetic neurons to inhibit the release of ACh and NE. This decreases BP.

232
Q

Hypothalamus

A

controls release of hormones via the pituitary and integrates information from may different signaling systems in body.

233
Q

Posterior pituitary - brain or gland?

A

brain

234
Q

anterior pituitary - brain or gland?

A

gland

235
Q

Subfornical organ

A

lacks a blood brain barrier so it can detect hormones and stretch receptors to detect BP –> sends signals to hypothalamus for ADH release.

236
Q

isotonic exercise

A

bike, jog, swim
decreases peripheral vascualr resistance and increases venous return.
Increase HR and increases inotropy
decreases afterload.

237
Q

Isometric exercise

A

weight training
increase peripheral vascular resistance
Increased HR
No increase in CO.

238
Q

what happens during a heart attack?

A

loss of functional myocardium
Increasec atecholamine surge to cause sweating, tachycardia, hypertension.
Increase Inotropy to maintain CO despite increased BP
Heterogenous cellular environment (some areas alive some dead) to affect cytosolic calcium

239
Q

Flow (Q) =

A

Change in pressure/change in resistant

240
Q

Cardiac Output =

A

(Pa-Pv)/Total peripheral resistance; or SVxHR

241
Q

Flow (Q) complicated equation

A

Change in press x (PiX r^4)/ 8 nl (viscosityXlength)

242
Q

Velocity =

A

Flow Q /cross sectional area

243
Q

Velocity is small area

A

Increased - Aorta

244
Q

Velocity in large area

A

decrease - capillaries

245
Q

Resistance in parallel

A

decreased total resistance (1 over)

246
Q

Resistance in series

A

Increased total resistance (additive)

247
Q

Pulse Pressure =

A

Pressure Systemic - Pressure diastolic

248
Q

Systolic pressure represents

A

peak aortic prssure

249
Q

Diastolic Pressure represents

A

minimum aortic pressure

250
Q

Mean arterial pressure =

A

Pdiastolic + 1/3(Pulse pressure)

251
Q

Compliance represents

A

how stretchy something is

252
Q

compliance =

A

change in volume/change in pressure

253
Q

what determines compliance

A

relationship between elastin and smooth muscle collagen; veins are more compliant than arteries

254
Q

La of LaPlace

A

Wall stress (T) = change is pressure*radius/u or wall thickness

255
Q

La of laplace in practical terms..

A

wall stress is inversely related to wall thickness. Thicker wall is less stressed —> hypertrophy

256
Q

Rate of bulk transport

A

Flow * concentration of substance

257
Q

Fick equation does this..

A

how much substance is used by the tissue

258
Q

Fick equation

A

X = Q ([x]initial-[x]final)

259
Q

How to calculate myocardial oxygen consumption

A

CO([O2 arterial]-[O2 venous])

260
Q

Fractional Oxygen Extraction

A

([O2art)-[O2vein])/[O2art]

261
Q

what determines oncotic pressure?

A

concentration of alpha globulin and albumin

262
Q

Flux or balance of hydrostatic and oncotic pressures

A

k[(HPc-HPi)-(OPc-OPi)]

263
Q

When is filtration favored?

A

when HP in capillaries is greater than interstitial fluid

264
Q

when is absorption favored?

A

when OP in capillaries is greater than interstital fluid

265
Q

What is the order of the phases in contraction

A

1) Filing 2) isovolumetric contraction phase 3) ejection phase 4) isovolumetric relaxation phase

266
Q

What phases are diastole?

A

1) filling and 2) isovolumetric relaxation

267
Q

Filing phase

A

Mitral valve is open because Atrial Pressure is higher than Ventricular pressure. Atrial systole occurs. Blood is flowing from atria into ventricle due to mitral valve being open.

268
Q

A wave

A

also known as atrial systole - start of atrial contraction from SA node. Occurs during diastolic filling phase

269
Q

Isovolumetric Contraction

A

depolarization/contraction reaches ventricles to increase ventricular pressure greater than atrial —> closes valve. Aortic/pulmonic valves remain closed. Ventricular pressure increases dramatically and volume remains constant.

270
Q

what closes the mitral or tricuspid valve in systole?

A

increased ventricular pressure over atrial pressure.

271
Q

in the isovolumetric phases, why are both the valves closed?

A

because aortic/pulmonic pressures are greater than those in the ventricles

272
Q

Ejection phase

A

when contraction is increased so much that ventricular pressure exceeds aortic or pulmonic pressure to open the valve. Ventricle begins to relax and slowly pressure decreases and blood is ejected.

273
Q

Isovolumentric relaxation

A

when ventricular pressure decreases to be below aortic or pulmonic presure, the valve closes (delayed). The mitral or tricuspid are still closed so volume remains constant.

274
Q

End Diastolic Pressure Volume Relationship

A

the filling phase - pre-load. A sign of the passive elastic properties of the heart. Slope of this line is inverse of compliance. Increased EDPVR is decreased compliance.

275
Q

Systolic Pressure Volume Relationship

A

Pressure at peak isometric contraction - afterload.
Represents active and passive elastic properties of heart.

276
Q

Active tension of heart

A

difference between End Diastolic VPR and SPVR..

277
Q

Factors of Active tension

A

1) heart fusions on the ascending curve.
2) EVPVR increases force of contraction (CO)
3) what goes out must come in CO = VR

278
Q

Frank Starling relationship

A

reflects intrinsic property of heart, independent of autonomic nervous system and dependent on sarcomere length-tension relationship.

279
Q

What is the molecular basis of the Frank Starling relationship?

A

1) Titin to resist stretch past optimal length
2) Ca sensitivity increases at longer sarcomere length
3) increase length changes lattice spacing to allow cross-bridge to generate more force.

280
Q

Mitral valve for ESV?

A

Open

281
Q

Mitral Valve for EDV?

A

closed

282
Q

Stroke Volume =

A

EDV - ESV

283
Q

Ejection Fraction

A

SV/EDV or (EDV-ESV)/EDV

284
Q

Stroke work

A

energy per beat (J) or the area under the curve. Left works more than right.

285
Q

Increasing preload results in…

A

preload represents EDV. So increasing preload increases Stroke volume on next beat.

286
Q

what factors affect preload

A

Blood volume, filling pressure, resistance to filling - arterial pressure, AV valve stenosis, Ventricular compliance.

287
Q

Decreased compliance in terms of prelaod

A

decreased compliance means hypertrophy, decreased EDV/preload

288
Q

Increased compliance in terms of preload

A

increased compliance leads to dilation, increased EDV and preload

289
Q

What factors affect afterload?

A

Aortic pressure, wall thickness and radius, aortic stenosis

290
Q

Increasing after load affects stroke volume

A

decreases stroke volume, because must increase pressure at same EDV to overcome that pressure and this increases the ESV (volume remaining).

291
Q

Inotropy

A

contractility - used in exercise and due to sympathetic and hormonal agents. Increasing isotropy increases stroke volume

292
Q

Increasing inotropy

A

decreases ESV to increase contractility. This is long acting though.

CVPR (12 decks)

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