Cardiovascular Physiology Flashcards
Windkesssel Effect
Pulsatile outflow of LV converted to continuous flow by:
1. elastic properties of aortic wall, large arteries - store ejected blood so act as a reservoir
2. presence of resistance in peripheral vessels
3. prevention of retrograde flow by aortic valve
Stored blood forced out into peripheral vessels during diastole - responsible for ~50% of peripheral blood flow in most animals during normal HRs
Cross Sectional Area and Flow
o Significant resistance to flow in small arteries, increases in arterioles = SLOWS velocity of blood
Ensures blood flow through capillaries = continuous, slow: favors diffusional exchange of nutrients btw tissues, blood
* Velocity in capillaries (LJ) 0.03cm/s
Which has a larger SA - pulmonary capillary beds or systemic?
Pulmonary capillary beds (4000 cm2 SA)»_space;> systemic capillary beds (2800 cm2 SA)
Vessel Types
o Elastic, Windkessel-type conduits = large arteries
o Resistance vessels = small arteries
o Sphincter vessels = arterioles
o Exchange vessels = capillaries
o Capacitance vessels = venules, veins
o Large conduits = veins
o Shunt vessels = arteriovenous anastomoses
Larger blood vessels (>100-200μm)
Macrocirculation
High pressure portion of circuit
Smaller Arteries
Greater % SmM vs elastic tissue –> increased control over vessel diameter, vascular resistance, regulation of blood flow
Densely innervation
Control distribution of blood flow
Site of 80% pressure drop btw aortic, VC
Resistance Vessels
Arterioles/metarterioles principal determinants of vol, distribution of blood flow: a1, a2 R
Thick, muscular walls
> 50% SVR
Arteriovenous Anastomoses
bypass capillary, connect arterioles to venules, allow shunting of blood
SmM
Greatest numbers in skin, extremities: thermoregulation
Capillaries
Microcirculation: <100um
Includes terminal arterioles, capillary networks, venules
Single layer of endothelium, large surface area for exchange of O2/nutrients/CO2
Continuous, non-fenestrated capillaries
Tight junctions
Located in all tissues of body except epithelia, cartilage
Functional pore size of approximately 5nm; permits diffusion of water, small solutes, lipid soluble materials
* Glycocalyx prevents loss of larger molecules, blood cells
Breaks within interendothelial cell junctions as a result of trauma, inflammation = primary path for transvascular fluid filtration, increase porosity
Special continuous, non-fenestrated capillaries
Central nervous system, enteric nervous system, retina, thymus
Endothelial cells bound together by tight junctions with effective pore size of <1nm
Responsible for BBB
Fenestrated Capillaries
Present in skin CT, kidney intestinal mucosa, endocrine, exocrine gland, choroid plexus
Absorb interstitial fluid into plasma
Allow for absorption/rapid exchange of water and solutes
Discontinuous/Sinusoidal Capillaries
Discontinuous, characterized by gaps between adjacent endothelial cells
interstitial fluid essentially part of plasma volume and sinusoidal tissues
Spleen, liver, bone marrow, endocrine organs
allows plasma proteins secreted by liver cells to easily pass through sinusoids, into bloodstream through pores 20- 280nm
Veins, Venules
Low-resistance conduits for return of blood to RA
Normally contain 60-70% blood vol during resting conditions– capacitance altered by SNS activity
o Veins 30x more compliant than arteries
High population of a1, a2 R – mobilize blood when needed (splanchnic circulation)
o Venous resistance (VM tone) = principal determinant of venous return, CO
Heart cannot pump more blood than receives
Layers of the Heart
Endocardium
Myocardium
Epicardium
Visceral Pericardium
Pericardial Sac
Parietal Pericardium
Fibrous Pericardium
Mediastinal Parietal Pleura
Role of Fibrous Pericardium
limits sudden overdistention of heart chambers
Coronary Vascular Anatomy
LV free wall, IVS: paraconal br L coronary a
Subsinuosal coronary: extension of L circumflex, majority of LV
R coronary: RV free wall - dominant in cats, horses
L coronary: dominant except in cats, horses
S1
Closure of AV valves when ventricular pressure > atrial pressure
S2
passive closure of semilunar valves (aortic, pulmonic) when ventricular pressure decreases during diastole
R-L Shunting during Anesthesia
Bypasses lungs: deoxygenated blood returns to systemic circulation
PSNS increases during apnea –> bradycardia, increases PVR –> promotes development of R-L shunt
Slows inhalant induction - effect more pronounced with less soluble anesthetics
L-R Shunt
Recirculates pulmonary venous (oxygenated) blood back into pulmonary circulation
Tachycardia, decreased PVR, increase L-R shunting coincide with ventilation
Can increase speed of IV induction
Main Substrate used by heart
non-esterified fatty acids (60% O2 consumption)
Type A Hearts
Dogs, cats, primates, rats
Type B Hearts
Cows, birds, small ruminants, horses, dolphins
Extensive His Purkinje system throughout
SmM Contraction
Involuntary non-striated muscle
Controlled by:
Receptor activation
Mechanical stretch activation of actin and myosin
Change in membrane potential
Basic Mechanism of SmM
increase cytosolic Ca, CICR from SR/through Ca channels from extracellular space, phosphorylation of light chain of myosin (MLC), Ca-calmodulin activates myosin light chin kinase (MLC kinase), interaction of myosin/actin and contraction
Contractile activity determined primarily by phosphorylation of light chain of myosin
Receptors Responsible for Ca Influx
- Voltage operated Ca channels
- Receptor Operated - blocked by Ca channel blockers
- Storage operated Ca Channels
How Decrease Ca from Intracellular
PMCA (plasma membrane Ca-ATPase pump), SERCA (sarcoplasmic reticulum Ca-ATPase pump), Na/Ca exchanger, Cytosolic Ca binding protein
NE, epi, AngTII, endothelin
Promote VC by binding to Gq GPCR –> increase intracellular [Ca]
How Inhalants Depress Myocardial Activity
Decreases IC Ca concentrations via blocking Ca channels (especially VOCCs )
Activation of Katp channels - K exiting, hyperpolarizaition (also activated during hypoxia, ischemia, acidosis, shock)
SkM Features
–Striated actin/myosin arranged in sarcomeres: 2 tubules/sarcomere
–Well developed SR, transverse tubules
–Troponin thin filaments
–Ca enters cytoplasm from SR
–Cannot ctx without nerve stimulation
CaM Features
–Striated actin/myosin arranged in sarcomeres: 1 tubules/sarcomere
–Moderately developed SR, transverse tubules
–Troponin thin filaments
–Ca enters cytoplasm from SR, ECF
–CAN ctx without nerve stimulation
SmM Features
–Not striated: actin»_space;> myosin
–Poorly developed SR, no transverse tubules
–Contains calmodulin: when bound Ca, activates MLC-K
–Ca enters cytoplasm from SR, ECF, mitochondria
–Maintains tone in absence of nerve stimulation
Structure and Function of CaM
Striated, branched m cells, single nuclei
Branching allows for fast signal propagation, contraction in three directions
Intercalated Disks
Mechanical anchoring points for cytoskeletal proteins
ensure transmission of contractile forces produced by individual cells
Allow rapid cell to cell communication via easy diffusion of ions btw cells
Gap junctions (connexons)
intercalated disks ensure rapid electrical communication btw cells, allows myocardium to act as functional syncytium, low electrical resistance
Desmosomes
anchor points to bring cardiac m fibers together, would otherwise fall apart during ctx
Adherens junctions
mechanical intercellular junctions, link intercalated disk to actin cytoskeleton
Anchor point where myofibrils attached
CaM Contractile Units
CaM –> myofibrils –> myofilaments –> sarcomeres in series (actin, myosin)
CamM Thick Filament
Myosin
CaM Thin Filament
Actin
2a helical strands of g-actin, interacts with myosin molecules to form cross bridges, ~300 molecules
Includes all the troponins
Tropomyosin
prevents free actin from interacting with myosin when CaM at rest, interspersed in actin filaments
Troponin
regulatory protein with 3 subunits
- Troponin C
- Troponin T
- Troponin I
Troponin C
binds Ca2+ ions during activation, initiates configuration changes in regulatory proteins that expose actin site across from cross-bridge formation
Troponin T
anchors troponin complex to tropomyosin
Troponin I
participates in inhibition of actin-myosin interaction at rest
Titan
macromolecule that extends from Z disk to M line, contributes significantly to passive stiffness of CaM over normal working stage
Doesn’t allow to get flaccid btw beats
Three MOA to Decrease IC Ca in CaM
- Increased activity of calmodulin - stimulates active extrusion of Ca by pumps in sarcolemma
- Increased activity of phospholamban to increase Ca uptake by SR
–Increased relaxation with beta stimulation - Enhanced activity of Na-Ca exchanger
Nerst Equation
Single ion’s equilibrium potential, equivalent to Vrev if channel singly selective for that ion
Goldman Katz Equation
Combined equilibrium potential of all relevant (permanent) ions
Provides RMP
Also provides Vrev of multi-ion channels
RMP Cardiac Cells
RMP cardiac cells: -90mV vs -65mV for nerves/m
Cells with more negative RMP have greater excitability, more rapid conduction velocity
More negative: atrial cells, ventricular cells, Purkinje cells
Less negative: SA, AV node cells; diseased myocardium
Speed of Cardiac APs
Cardiac APs (150-300ms) > nerve APs (1-3ms) DT prolonged plateau phase from changes in membrane permeability to calcium
Also greater in magnitude change 130mV vs 80mV
Long QT syndrome
Related to repolarization currents (IK) DT importance in determining AP duration
* Uncommon condition in people in which delayed repolarization of heart increased risk TdP predisposing to vfib
Related to phase 3/outward movement of K
Absolute Refractory Period
200ms
threshold for depolarization is infinite, ie no stimulus, no matter how great, will be able to make the myocyte depolarize again
* VG Na channels: will not open until MP < -40mV
Relative Refractory period
50ms
stimuli of normal magnitude do not produce any depolarization, unnaturally large stimuli can produce depolarization of lower magnitude
* Fewer Na channels available so takes larger stimulus to activate, trigger depolarization
* If depol does occur, still too few to make proper Phase 0 spike lower amplitude phase 0
Functional/Effective Refractory Period
combo of absolute and relative; cell cannot produce AP that could depolarize surrounding muscle
* Depol completely impossible or because ends up being so useless that cannot trigger depolar of adjacent cells
Supranormal Period
repolarization reaches nadir which slightly below RMP, creates hyperexcitable period during which weaker, subnormal stimulus could trigger depolarization and produce AP
RMP SA, AV Nodal Cells
max neg diastolic threshold -65mV
RMP Purkinje network, atrial specialized pathways
Purkinje network, atrial specialized pathways -90mV
L Type Ca Channels
AKA dihydropyridine R
Predominant Ca channels in heart, VG
Begin to open during AP upstroke (phase 0) when membrane depolarized to -10mV,
Blocked by Ca Channel Blockers
Long Lasting
T Type Ca Channels
Transient
Open during phase 0 when membrane potential -60 to -50mV, VG
Not affected by catecholamines, Na channel blocks, Ca antagonists
T Type Ca Channels
Funny Current
Na, Ca, K - predominantly Na in PM cells
Contributes to slow depolarization during diastolic interval
Progressive decrease in membrane permeability to K, increased permeability to Na
Also have changes in Ca permeability at end of diastole where increase in permeability/inward movement of Ca - contributes to diastolic depolarization
Activated by hyper polarization
SaN
PM = determines HR) DT slow spontaneous diastolic depolarization of membrane, fastest in SA nodal cells
Cells usually reach TP, fire before any other cells
AVN
slowed as passes through AV node: small size of AV nodal cells, slow rate of rise of their AP, low RMP (-60mV)
AV node delays transfer of cardiac excitation from atria to ventricles = allows atrial ctx to contribute to ventricular filling before ventricles begin to ctx
Why Pause at AVN (0.1msec)?
ATRIAL KICK, up to 20% of CO – DELAY IS IMPORTANT TO ALLOW ATRIA TO CONTRIBUTE TO VENTRICULAR FILLING
AV nodal cells have faster depol than all other areas of heart except SA node latent pacemaker
Ventricular Cells
last to depol, first to repol (short duration APs)
AP ~1msec
Purkinje Cells
+midmyocardial cells at middle of ventricular walls have longest AP
serve as physiological gates to prevent reentry, recycling of electrical impulses in ventricular myocardium
Overdrive Suppression
Purkinje cells have capacity to spontaneously depolarize via funny current, usually concealed by own slow depolarization rate (40-50bpm)
What are the two most proarrhythmogenic changes of the cardiac AP?
slowing of repolarization (triangulation), slowing of conduction
Triangulation
Altering duration, shape of AP, RP, impulse conduction velocity creates regional heterogenous differences
Leads to creation of re-entry circuit
Altered Conduction
important parameter for determining product of conduction velocity x refractory period
