Flashcards in CV Test 1 Deck (292):
Phase 0 of Fast Action Potential
Rapid upstroke due to Na entry into the cell
Phase 1 of Fast Action Potential
Partial repolarization to OmV
Due to inactivation of Na channels and activation of IKTO to have K efflux
What channel is responsible for Phase 1 of Fast AP?
IKto channel; Kv.4.3 tetramer with Khip2 - voltage dependent activation and inactivation
Phase 2 of Fast AP
Prolonged Plateau phase. Balance between Outward Potassium flow (IKR and IKS) through delayed rectifier channel and inward Calcium flow though LTCC.
Delayed Rectified K channels
delayed in activation and are responsible for the plateau phase of Fast AP and the rapid repolarization of Phase 3
Phase 3 of Fast AP
Rapid hyperpolarization due to inactivation of Ca Channel and increasing activation of IKR and IKS
Phase 4 of Fast AP
Absolute refractory period. Deactivation of IKR and IKS, activation of inward rectifier IKI to keep near Ek.
Channel more active in Phase 4 of Fast AP
IKI (inward rectifier K )
Where are slow Cardiac Action Potentials located?
SA and AV nodes
What are the major channels differences between slow and fast AP producing cells?
Reduced expression if INa and IKI chennels; increased expression of IF and ICaT.
Phase 0 of slow AP
slow upstroke due to activation of ICaT and ICaL. NO activation of Na channels
Phase 1 of slow AP
does not exist!
Phase 2 of slow AP
does not exist
Phase 3 of slow AP
Repolarization - balance between Ca and delayed rectifier current IKR and IKS.
Phase 4 of slow AP
Pacemaker Potential due to hyperpolarized triggered IF (cation fluxes to drive slow depolarization to -30mV).
Nav1.5 - voltage dependent actiation and inactivation
L type and T Type
L type Ca Channel; Cav1.2 and Cav1.3 that are high voltage activated, and voltage and [Ca} deactivated.
T type Ca Channels
Cav 3.1 and 3.2; Low voltage activated and voltage deactivated; only present in nodal cells
IKto, Delayed Rectifier (IKR and IKS), Inward rectifiers - IKi and GIRK
Kv4.3 tetramer with KCHIP2, voltage dep act and inactivation; only in fast AP to cause brief hyperpolarization
IKr and IKs
delayed rectifier K channels. HERG (IKr) and KvLQT (IKs)
Time dependent Cation channel in pacemaker cells that are Na and K permeable; activated with hyperpolarization.
Kir tetramer - inward rectifier channel, inward K whens lighly above Ek
IKACh, activated by muscarinic recpetors, slows pacemaking
What does the R phase correspond to in the channel cycle?
Phase 0 - opening of Na Channels
What does ST phase correspond to in the channel cycle?
What does T phase correspond to in the channel cycle?
atrial depolarization/contraction 0.08-.1 seconds
vent. contraction 0.06-0.10
Conduction time across AV node 0.12-0.2 sec
Total depol and repol of ventricle times less than 0.44 sec
Path of depolarization of ventricles
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
Repolarization of ventricles
in opposite direction becuase endocardium depolarizes before epicardium, but epicardium repolarizes before endocardium.
what causes first degree AV node block?
transiet reversible influence or structural defect; heightened vagal tone, transient AV node ischemia, drugs that depress conduction of AV node, MI degeneration
what causes a second degree AV node block?
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.
What causes third degree AV node block?
acute MI and chronic degeneration that causes separation between conduction of atria and ventricles
Sympathetic regulation of Inotropy
NE binds to Beta-Andrenergic receptors to activate GalphaS to target AD and increase cAMP and PKA activation..
4) Phospholamban (PLB)
Phosphorylation of DHPR
by PKA to increase inotropy... the effect is slowed deactivation to increase calcium entry and increase Calcium induced calcium release.
Phosphorylation of RyR
Increases sensitivity to calcium and increases calcium release to increase inotropy and chronotropy
Phosphorylation of Tn-I
Phosphorylation of Tn-I by PKA decreases Tn-C's sensitivityt to calcium to cause faster dissociation and increase lusitropy. Does not effect inotropy.
Phosphorylation of PLB
relieves the inhibition on SERCA, so that SR uptakes Ca faster. Increase Inotropy and lusitropy.
what controls HR at rest?
both parasympathetic and sympathetic neuronal control
Sympathetic control of chronotropy
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
cAMP binding to HCN
causes increased depolarization (If - inward movement of Na and K) and increase excitability to lead to more APs
parasympathetic control of Chronotropy
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.
Sympathetic Control of Vasculature
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.
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.
What controls vasodilation
not necessary parasympathetic response, but less sympathetic activation.
low pressure in atria and vena cava trigger baroreceptors to mediate increase in Heart rate
Vasoactive Metabolites in vasocontrol
local feedback to control vasodilation and constriction. Triggered by PO2, PCO2, pH, extracellular K, adenosine.
why does extracellular K act as a metabolite
ATPase can't keep up and indicates lots of activity and vasodilation
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.
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
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.
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
Control mechanism for endothelin
ET-1 binds to ETR receptor on endothelial cell to act on NO synthase enzyme to promote production of NO - vasodilator
what triggers Renin release
sympathetic stimulation, hypotension, decrease Na delivery (kidney secretes its)
Effects of Angiotensin II
Cardiac and Vasculature hypertrophy
stimulate adrenal cortex to increase aldosterone release
stimulate pituitary to release anit-diuretic hormone/vasopressin
hormone released from adrenal cortex in response to AnII to cause Na and Fluid retention.
Anti-diuretic Hormone or Vasopressin released from pituitary with AnII to cause Na and Fluid retention, as well as vasoconstriction
Atrial Natiruetic Peptide is a vasodilator that is released due to atrial stretch
effects of ANP
decreases renin release to decrease vasopressin and aldosterone release.
drecreases endothelin release
decreases vascular resistance
Increase fluid egress
ANP bind to NPrecpetor to active gunylate cyclase direction (Not GPCR) to increase cGMP and activate SERCA and Na and H20 excretion.
Forward Heart Failure
inability for CO to meet metabolic demands of the body, due to low Cardiac output
Backward heart Failure
filling pressures are abnormally high to meet demands of the body, increased congestion.
what fails in HF?
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)
What contributes to SV?
Increased inotropy and preload and decreased afterload
Loss of contractility due to weak or damaged myocardium. Decreased inotropy to cause increase ESP and decreased SV.
examples of systolic HF
Decreased ejection fractio (HFrEF, LV systolic dysfunction); Ventricular enlargement (dilated cardiomyopathy).
Systolic HF is due to..
direct destruction of Heart muscle cells via MI or other cuases
2) Overstressed Heart muscle - meth, cocaine
3) Volume Overload - mitral regurgitation
Stiff or non-compliant heart due that decreases pre-load and lusitropy. Requires increased pressure to achieve same filling volume and ultimately increases ESP
Diastolic HF samples
Normal ejection fraction : HFpEF, preserved systolic function
Diastolic HF is due to..
Increaesed afterload - hypertension, aortic stenosis, dialysis
Myocardial fibrosis - hypertrophic cardiomyopathy
External compression - pericardial fibrosis, effusion
Right sided HF is due to..
Left sided HF
Lung disease or pulmonary Hypertension, "cor pulmonale"
RV overload - due to shunt, tricuspid regurgitation
RV myocardium damage
Neurohormonal action in heart failure
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.
During pregnancy and chronic exercise. Myocyte length> myocyte width with no fibrosis. General increase in chamber size and no dysfunction.
What leads to cardiac dilation?
MI, Dilated cardiomyopathy, pregressio from pathological hypertrophy.
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.
What causes pathological hypertrophy
chronic hypertension and aortic stenosis
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.
high ATPase acitivity, more effective at contraction
low ATPase activity, less effectie at contraction. In HF shift to Beta myosin
Changes in calcium regulation in HF
increase Ltype Ca Channel and decrease in SERCA function (increased PLB), to cause increased cyto Calcium levels and decrease lusitropy.
Changes in gene expression in HF
early acute: PKA and PKC activation
chronic: PKE, PKD, CAMK (calcineurin)
A Ca dependent phosphatase that remove Phosphate from NFAT to dead to cardiac remodeling
Smooth vs. Striated Muscle
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)
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.
PKA in cardiac vs VSCM?
PKA promotes contraction via phosphroylation of Ca entry into cyto (cardiac cells)
IN VSMC pKA regulates phosphorylation of MLCK to influence contraction.
Class I Anti-arrhythmics
Na Channel blockers that mostly affect fast response cell. Decrease conduction velocity and increases effective refractory period. Use Dependent.
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.
Decreasing conduction velocity - class I
converts unidirection block into bidirectinla block - so signal cant propagate into a depressed region.
Two conditions necessary for re-entry
1) unidirectional block 2) conduction time > refractory
How to terminate re-entry?
1) convert unidirection block to bidirectional block 2) prolong refractory period
drug that selectively targets overactive cells (channels open) and stabilize the cell in the inactive state to prolong the refractory period.
First antiarrhythmic drug - Class Ia
In addition to Na block; Blocks K channels to prolong AP
Anti Cholinergic (vagal inhibitor)
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.
Propafenone, Flecainide, Encainide
Markedly slow upstroke
prolonged phase 2
delayed repolarization due to K channel block
so of the Class I drugs, which on has the slowest upstroke?
which Class I shows delayed repolarization
A > C, B is shortened repolarization
Class I drugs - which ones have extended refractory period?
all - all are use dependent.
Class II anti-Arrhythmic
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.
Class II examples
Propanolol, Metorpolol, Esmolol
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.
Examples of Class III
Ibutilide, Dofetilide, Amiodarone, Sotalol, Bretylium
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.
Class III, but also acts as beta blocker
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
Class IV examples
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
What cell types are in the heart
Endothelial cells>cardiac fibroblasts>mycocytes
mediate ECM of heart, lay down foundation upon which myocytes function
ECM in heart it made up of..
fibrillar collagen type I and III
Cardiac vs. skeletal muscle
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
connect cardiac muscle cells, coincide with Z discs and contain desmosones and gap junctions.
adhesion and assures force generated in one cell is transfered to the other, connects to ECM
what makes up the maorjity of the heart cell volume?
myofibril and mitochondria. The rest is sarc, T tubule, SR, intercalated disks, gap junctions
single muscle cell containing the usually orgnaless plus many myofibrils
end to end array of idential sarcomeres
unit of contractile activity - composed of actin and mysoin and estends from Z line to Z line.
does tropomysin and troponin interact with actin or myosin?
dumbell shaped; N lobe with ONE Ca binding site.
N terminal extension of 32 amino acids that contain PKA phosphoryltion site for adregnergic responsiveness. Interacts with TN-C but is released with phosphorylation.
binds to tropomysin. N terminal regulated with Calcium sensitivity.
alpha form in heart; lies over myosin binding sites.
Relaxation cycle on contraction - molecular mechanism
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.
Diastole - Actin Myosin Relationship
1) Resting state: No Ca, non force generating
2) Transition state: Ca bound, non force generating
Systole Actin Myosin relationship
3) Active State: Ca bound force generating
4) Active state: No Ca bound, force generating
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.
N2B and N2Ba
titin isoform that is stiff
titin isoform that is not very stiff
length tension relationship
increasing muscle length increases muscle tension
Mechanisms behind the Length Tension Relationship
1) extent of overlap
2) change in calcium sensitivity
3) increased calcium release
How does extent of overlap affect length tension relationship
peak tension develops at lengths of 2.3 an 2.2 uM. This indicates that muscles are a prime length for tension development.
How does changing calcium sensitivity affect length tension relationship?
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.
How does increased calcium release affect the length tension relationship?
occurs several minutes after changing muscle length - due to stretch sensitive channels in cell membrane.
What factors regulate calcium sensitivity of the myofilament?
TnT Isoform composition
TnT Isoform and Calcium sensitivity
N-terminal extension of TnT decreases sensitivity to calcium
PKA phosphorylation of TnI and calcium sensitivity
Phosphorylation decreases Ca sensitivity to TnC, to promote lusitropy.
Force Velocity Relationship
increasing preload enables muscle to contract faster against a given afterload
what change velocity at sarcomere level?
Phosphorylation of MLC
Phosphorylation of MyBPC
Ventricle Geometry and Muscle Fibers
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.
Concentric Vs Eccentric hypertrophy
Concentric - increase n muscle width - pathological hypertrophy
Eccentric: increase in muscle length - dilation
in atria and ventricles that are quire large -20 um in diameter
in SA and AV nodes and are smaller, specialized for electrical conduction instead of contraction.
What supplies Right atrium and Right ventricle with blood?
Right Main coronary Artery
Left main coronary Artery supplies..
left atrium and ventricle with blood and bifurcates into left anterior descending (LAD) and circumflex.
Aorta - Types of Vessel
Large single outflow form heart with elastic and smooth muscle fibers in wall to dampen pulsatile flow. 2mm thickness 12 mm radius
Arteries - type of vessel
Thick walled (1mm) and resistnat to expansion.
Diameter 4 mm
Distribute blood to organs
Arterioles - type of vessel
Relatively thick wall with lots of VSMC (20um);
diameter 15 um
highly innervated - primary site of regulation of vascular resistance.
Thickness of arteries.
Venules and Veins type of Blood Vessles
Thin walls of similar diameters of arteries.
Capacitance vessels that hold most of the blood volume.
Low pressure - one-way valves
Large diameter 50 mm with very thin walls 1.5 mm, very low pressure.
outermost layer of vessel that contains connective tissue like collagen and elastin
mIddle layer of vessel that innervated smooth muscle cells. Controls vessel diameter
Inner layer with connective tissue and vascular endothelium.
Important site of signaling
Site of plaque formation.
smooth muscle bands at junction of arterioles and capillaries to regulate blood flow through capillary beds
Lymph is filtered interstitial fluid that is filter and is run through the lymphatic system which is low pressure with one-way valves.
What promotes flow of lymph?
increased interstitial pressure, smooth muscle contraction of lymph vessels, contraction of surrounding skeletal muscles
when SA node is overtaken by an ectopic pacemaker to trigger contraction independently.
located a right side of heart near opening of coronary sinus to regulate action potential propagation through ventricles.
How does signal spread from AV node"?
through conducting pathways that propagate to L and right ventricles that are larger in diameter and able to spread the signal rapidly.
what prevents the depolarization from spreading from atria to ventricles, besides AV node?
CT electrical insulation
T-Tubule Lumen Ca Concentration
less than 2 mM
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.
binds to Ca in terminal SR with low affinity and high capacity. Low binding affinity, but high storage capacity of calcium.
why isn't calcium entry from DHPR sufficient for contraction?
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.
DHPR - L Type Ca Channel.
Four homologous repeat subunits. Binds to Beta, and alpha2delta subunit.
enormous homo-tetramer in SR that binds to ryanidine with high affinity. From different physiological pathway than DHPR
Cardiac vs Skeletal muscle calcium
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.
Cav1.2 2-3 loops
can be replaced with Cav1.1 loop to couple cardiac to skeletal type contraction.
Why is SERCA most important in cardiac cytoplasmic Ca removal?
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.
3 Na in for 2 Calcium out; net effect is that it depolarizes the membrane.
Can switch direction based on membrane potentials and concentrations.
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..
Consequences of over NCX use?
depolarization triggers abnormal diastolic SR Ca release to trigger delayed afterpolarizations and gives rise to arrhythmias
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.
Result of Phosphorylation of DHPR
increased inotropy - contractile force
Result of Phosphorylation of RyR
Result of PLB phosphoryaltion
increase inotropy and lusitropy
Phosphorylation of Tn-I
why are genetic disorders of EC coupling difficult to study?
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
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
Timothy syndrome symptomes
syncope, arrhythmia, sudden death, intermittent hypoglycemia, immune deficiency, cognitive abnormalities - autism
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>
Brugada mutation - Cav1.2 and B2B mutation EKG
Shortened QT interval
Catecholaminergic Polymorphic ventricular Tachycardia
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
CPVT - Treatment
For some patients, need to prevent release of RyR with Tetracaine OR block Na channels like Flecainide
Function of ANS
maintain homeostasis within a narrow physiological range amid changing external conditions.
ANS vs SMS
ANS: involuntary, diffuse, slow AP, innervates smooth, cardiac and gland muscles, disynaptic
Somatic: voluntary, specific projections, rapid, innervates skeletal muscle, monosynpatic
what does disynpatic mean for ANS?
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.
located in the medulla - contains nucleus of ANS neurons that convey visceral sensory input
in forebrain, conveys internal goals and states.
Myelination of pre and post ganglionic neurons
Pre are myelinated, post are nonmyelinated
Sympathetic NS - where do nerves originate compared to parasympathetic
S: thoracic and lumbar spinal cord
P: brainstem and sacral spinal cord
Where are the ganglia located in sympathetic vs parasympathetic?
S: near spinal cord in sympathetic chain
P: near target organs
Ratio of Pre to post ganglionic neurons in sympathetic vs. parasympathetic
Sympathetic have many more post ganglion than pre 10:1
Parasympathetic have more post than pre as well, but only 3:1
sympathetic nerves exit the spinal cord via the ventral roots and pass through this myelinated section before entering the sympathetic trunk.
How do parasympathetic pre-ganglionic nerves reach their ganglion?
In the brainstem they exit the via cranial nerve III (oculomotor), VII (facial), IX (glossopharyngeal), an X (Vagus).
PreGanglionic NT for Symp and Para
PostG NT for Sym and Para
exit out of sympathetic trunk with unmyelinated post-ganglionic fibers that project to sweat glands, blood vessels, viscera etc.
Are ACh receptor inotrophic?
Yes! Nicotinic receptors are
Type of ACh receptors?
Nicotinic *ionotropic) and muscarinic
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.
a ACh that is present on effector cells of cardiac muscle, smooth muscle and glands.
a GPCR that either stimulates or inhibits intracellular effectors
Alpha or Beta adrenergic
Alpha 1 Receptor
responsible ror vasoconstriction of skin
Gq acts on PLC --> IP3 and DAg
Agonist for A1
Antagonist for A1
Alpha 2 Receptor
presynaptic inhibition of NE release to cause mixed effects.
Acts via Gi to inactive adenylate cyclase
increases HR by activating Gs to activate cAMP
B1 Receptor agonist
B1 Receptor antagonist
increased HR and vasodilation in skeletal muscle, smooth muscle relaxation.
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.
mimics activation of sympatheic NS
Sympathetic stimulation of HR
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
Parasympathetic control of HR
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.
mimic sympathetic activity by activating sympathetic or inhibiting parap
mimic para by activating para or inhibit sympth
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.
High BP and baroreceptor
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.
controls release of hormones via the pituitary and integrates information from may different signaling systems in body.
Posterior pituitary - brain or gland?
anterior pituitary - brain or gland?
lacks a blood brain barrier so it can detect hormones and stretch receptors to detect BP --> sends signals to hypothalamus for ADH release.
bike, jog, swim
decreases peripheral vascualr resistance and increases venous return.
Increase HR and increases inotropy
increase peripheral vascular resistance
No increase in CO.
what happens during a heart attack?
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
Flow (Q) =
Change in pressure/change in resistant
Cardiac Output =
(Pa-Pv)/Total peripheral resistance; or SVxHR
Flow (Q) complicated equation
Change in press x (PiX r^4)/ 8 nl (viscosityXlength)
Flow Q /cross sectional area
Velocity is small area
Increased - Aorta
Velocity in large area
decrease - capillaries
Resistance in parallel
decreased total resistance (1 over)
Resistance in series
Increased total resistance (additive)
Pulse Pressure =
Pressure Systemic - Pressure diastolic
Systolic pressure represents
peak aortic prssure
Diastolic Pressure represents
minimum aortic pressure
Mean arterial pressure =
Pdiastolic + 1/3(Pulse pressure)
how stretchy something is
change in volume/change in pressure
what determines compliance
relationship between elastin and smooth muscle collagen; veins are more compliant than arteries
La of LaPlace
Wall stress (T) = change is pressure*radius/u or wall thickness
La of laplace in practical terms..
wall stress is inversely related to wall thickness. Thicker wall is less stressed —> hypertrophy
Rate of bulk transport
Flow * concentration of substance
Fick equation does this..
how much substance is used by the tissue
X = Q ([x]initial-[x]final)
How to calculate myocardial oxygen consumption
CO([O2 arterial]-[O2 venous])
Fractional Oxygen Extraction
what determines oncotic pressure?
concentration of alpha globulin and albumin
Flux or balance of hydrostatic and oncotic pressures
When is filtration favored?
when HP in capillaries is greater than interstitial fluid
when is absorption favored?
when OP in capillaries is greater than interstital fluid
What is the order of the phases in contraction
1) Filing 2) isovolumetric contraction phase 3) ejection phase 4) isovolumetric relaxation phase
What phases are diastole?
1) filling and 2) isovolumetric relaxation
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.
also known as atrial systole - start of atrial contraction from SA node. Occurs during diastolic filling phase
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.
what closes the mitral or tricuspid valve in systole?
increased ventricular pressure over atrial pressure.
in the isovolumetric phases, why are both the valves closed?
because aortic/pulmonic pressures are greater than those in the ventricles
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.
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.
End Diastolic Pressure Volume Relationship
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.
Systolic Pressure Volume Relationship
Pressure at peak isometric contraction - afterload.
Represents active and passive elastic properties of heart.
Active tension of heart
difference between End Diastolic VPR and SPVR..
Factors of Active tension
1) heart fusions on the ascending curve.
2) EVPVR increases force of contraction (CO)
3) what goes out must come in CO = VR
Frank Starling relationship
reflects intrinsic property of heart, independent of autonomic nervous system and dependent on sarcomere length-tension relationship.
What is the molecular basis of the Frank Starling relationship?
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.
Mitral valve for ESV?
Mitral Valve for EDV?
Stroke Volume =
EDV - ESV
SV/EDV or (EDV-ESV)/EDV
energy per beat (J) or the area under the curve. Left works more than right.
Increasing preload results in…
preload represents EDV. So increasing preload increases Stroke volume on next beat.
what factors affect preload
Blood volume, filling pressure, resistance to filling - arterial pressure, AV valve stenosis, Ventricular compliance.
Decreased compliance in terms of prelaod
decreased compliance means hypertrophy, decreased EDV/preload
Increased compliance in terms of preload
increased compliance leads to dilation, increased EDV and preload
What factors affect afterload?
Aortic pressure, wall thickness and radius, aortic stenosis
Increasing after load affects stroke volume
decreases stroke volume, because must increase pressure at same EDV to overcome that pressure and this increases the ESV (volume remaining).
contractility - used in exercise and due to sympathetic and hormonal agents. Increasing isotropy increases stroke volume