Introduction to the Cardiovascular System Flashcards
Main functions of the heart
provide the force necessary to pump oxygenated blood and nutrients throughout the body, maintain blood pressure and blood flow, receive deoxygenated blood and CO2 from the body and pump it to the lungs for reoxygenation and exhaling of CO2, generate hormones (ANF) and circulate this and other vital substances to different parts of the body
Main functions of the circulatory system
To transport nutrients, gases and waste products around the body, to help regulate blood pressure and blood flow to tissues as movement or metabolic demands change (exercise, position, blood loss), to protect the body from blood loss and infections, to help the body maintain a constant body temperature, to help maintain fluid balance within the body, humoral communication
Electrical impulses are normally initiated in the
Sinoatrial (SA) node
From the SA node, the waves of depolarization propagate along
three internodal tracts (anterior, middle, and posterior) across the right atrium to the atroventricular node (AV)
The AV node
delays the electrical signal for ~120 msec to allow the atria to empty of blood
From the AV node, the wave of excitation
continues down the bundle of His or atrioventricular bundle
The bundle of His consists of
wide, fast-conducting muscle fibers that carry cardiac impulses through the insulating annulus fibrosis in the fibrous upper part of the ventricular septum, after which it bifurcates to become the left bundle branch and the right bundle branch
These branches carry
the electrical signal to the Purkinje fibers, which are specialized conducting fibers that are composed of electrically excitable cells that are larger than cardiomyocytes
His-Purkinje System
No electrical connection between atria and ventricles other than the Bundle of His
The Purkinje Fibers conduct
cardiac action potentials more quickly and efficiently than any of the other cells in the heart’s electrical conduction system
Consequences of inappropriate conduction
Arrhythmias
Cardiac myocytes (cardiomyocytes)
basic unit of contraction in the heart (20-50 um - 100-200 um) (mononucleated or binucleated)
Sarcolemma
maintains the intracellular milieu, transports substrates into and out of the cell, serves as a location for intracellular and extracellular proteins to attach, transmits excitatory impulses that lead to contraction
Major sarcolemma proteins
Na-K ATPase, L- and T-type calcium channels, Na-Ca exchanger, Na channels, K channels
Three types of membrane junctions exist within an intercalated disk
Fascia adherens (intermediate junction), macula adherens (desmosomes), gap junctions
These adhesion junctions
mechanically stabilize the sarcolemmas of adjacent cells allow formation and maintenance of large arrays of intercellular channels (gap junctions)
Fascia adherens and desmosomes are characterized by
a much wider intermembrane space (25nm) than that of gap juction
Intercalated disks (ICDs) are
highly organized components of cardiac muscle which maintain structural integrity and synchronized contraction of cardiac tissue
Fascia Adherens (Adherecs junctios)
broad intercellular junction both of sarcolemma and intercalated disc, are anchoring sites to the actin cytoskeleton important for the maintenance of tissues and connect to the closest sarcomere
Desmosomes
macula adherens prevent separation during contraction by binding intermediate filaments joining the cells together
critical adhesion structures in cardiomyocytes, mediate direct cell-cell contacts, provide anchorage sites for intermediate filaments (desmin) important for maintenance of tissue structure, prevent the cells from pulling apart during the stress of individual fibers contracting
Gap Junctions
electrically couple cardiac myocytes and serve as low resistance electrical pathways that ensure safe conduction and allow the heart to function as an electrical sycytium
Sarcoplasmic Reticulum in cardiomyocytes
close association with T-tubules, form Dyad Junctions, sarcotubular network (transverse SR) and Cisternae (junctional SR)
Major proteins involved in Ca++ flux
sarco(endo)plasmic reticulum ATPase, Phospholamban, Calsequestrin, SR calcium release channel (ryanodine receptor)
Three filaments
Thick-myosin, thin-actin, elastic-titin
Arteries regulate inner diameter by
contraction of smooth muscle cells (tunica media)
Venous valves
prevent backflow of venous blood
Vascular Smooth Muscle Cells
predominant cellular component found within tunica media
no pacemaker activity
under control of autonomic nervous system and stretch generally cannot cause contraction
regulate vascular tone
maintain structure of blood vessel
thickest in largest arteries, absent in capillaries, thin in veins
General structure of smooth muscle cells
are small, mononucleated, fusiform (spindle) shaped cells, arranged circumferentially
end to end junctions couple the cells, increased surface area for both mechanical tight junctions and electrical coupling via gap junctions
do not contain the complex t-tubule/sarcoplasmic reticulum system common to striated muscles (no dyads), contain caveolae
Gap junctions in vSMCs
no intercalated discs
The aorta
a sparsely innervated and electrically quiescent vascular tissue that may be largely dependent on intercellular communication through gap junctions for coordination of smooth muscle responses
Small muscular arteries are innervated to
regulate blood flow and pressure
Synchronization of vasomotor tone among the smooth muscle cells is
critical for the function of blood vessels
The vascular gap junctions are assembled from one or more of four connexin proteins
Cx37, Cx40, Cx43 (predominant form in vasculature), and Cx45 (only in SMCs of vasculature)
Dense body
analogous to the Z-discs of skeletal and cardiac muscle fibers and is fastened to the sarcolemma, actin filaments are anchored to them
The “Latch” mechanism
facilitates prolonged holding of contractions of smooth muscle (prolonged tonic contraction for hours with little use of energy)
Electrical versus pharmacomechanical coupling
Calcium can enter the SM cell two ways
electrical depolarization results in increased Ca entry via the voltage gated channels
Receptor-coupled stimulation involves G-coupled receptors to release calcium from intracellular stores. No electrical activation required
Layers of smooth muscle cells line
the walls of various organs and tubes in the body, and the contractile function of smooth muscle is not under voluntary control
Contractile proteins
actin and myosin are not organized in a sarcomere structure, but form strut-like cables that alter force
Contractile activity in smooth muscle is initiated by
a Ca++ calmodulin interaction to stimulate phosphorylation of the light chain of myosin-phosphorylation sensitizes the myofilament to calcium
Ca++ sensitization of the contractile proteins
is signaled by the RhoA/Rho kinase pathway to inhibit the dephosphorylation of the light chain by myosin phosphatase, thereby maintaining force generation
Relaxation is
mediated primarily by the activity of MLC phosphatase
Calcium entry is
via voltage, receptor-coupled, or stretch activated channels triggers constriction
Removal of Ca++ from the cytosol and stimulation of myosin phosphatase (and desensitization of the contractile protiens)
initiate the process of smooth muscle relaxation
Potassium exit via several types of regulated channels triggers
relaxation or causes hyperpolarization to inhibit activation
What is a capacitor?
a charge storing device
two conductors separated by an insulator
What is capacitance of parallel plate capacitors?
Capacitance is determined by the overlapping plate area (A), the distance (d) between the conductors (plates), the permittivity (e) of the insulator
C = eA/d
The charge Q on the plates is
proportional to the potential difference V across the two plates
Capacitance C
the ability to store charge and it is the proportional constant Q = CV, C = Q/V
directly proportional to the area of the plate
inversely proportional to the distance between the plates
Lipid Bilayer as a capacitor
As positive charge builds up on the inside of the membrane, they repel positive charges away from the outside of the membrane. Basically, an electric field over a distance corresponds to a voltage difference
Electric field
the difference between the excess positive charges and the excess negative charges on the two membranes
The separation of charges across a membrane
produces a potential difference between the two sides
The displacement of charge
occurs due to a Capacitance current (Ic) through a membrane deltaQ = CdeltaV where Ic(t) = dQ/dt = C * dVm/dt
Kirchoff’s 1st law
the current flowing into a node (or a junction) must be equal to the current flowing out of it : -Ic + Ie = 0 –> the sum of all currents into a node is zero
From the capacitance current (deltaQ = C*deltaV), the total change in Voltage is given by
deltaV = 1/C * deltaQ
Since I(t) is equivalent to dQ/dt, then Vm(t)
= V0 + I0/C*t
Ie (electric current) =
IL (membrane ionic current) + CdV/dt (membrane capacitive current)
Ohm’s Law
Vm = RL * Ie
V(t) =
V(infinity) + (V0 - V(infinity))e^(-t/tau)
tau
defined as the product RC (resistance and capacitance of the membrane)
Conductance G
= 1/R
Conductances in parallel
add together
IL
= GLVm = AgLVm
gL
specific membrane ‘leak’ conductanceA
A
membrane area
Positive currents
outward currents
Negative currents
inward currents
Capacitance in parallel also add and scales with area
C = CmA, A = 4pir^2
Cm = specific capacitance/unit area of membrane
A = area
Membrane time constant
taum = RLC = C/GL = cmA/gLA = cm/gL
tau is only
a property of the membrane, and it is not dependent on cell size
What is the weakness of this cell system?
it relies on external curret
RL = leak resistance
Ie = injected current
IL = leak current from channels
Ic = capacitive current
By having a battery, we have the basis for the HH model where
some ion channels push the membrane potential to be positive
some ion channels push the membrane potential to be negative
the voltage difference among all these currents is the ‘battery’. moreover, the additive effects of these channels/currents give the cells machinery that is flexible to control Vm
Fick’s first law
Movement of particles (diffusion flux) from high to low concentration is directly proportional to the particle’s concentration gradient
J = -D (change in concentration of the particle)/(change in position) = -D (concentration gradient of the particle)
In one dimension: the molar flux of diffusion is proportional to the negative of the concentration gradient, a positive J is in the direction of the negative spatial slope of the concentration
Fick’s Second Law
States the relation between the change in concentration gradient of the particles and time
change in concentration with time = D * it’s second derivative
relates changes in concentration with time with the spatial distribution of solute particles ie. it allows one to determine concentration as a function of time and position (C(x, t))
Flux = -P(C2-C1)
P = permeability, C2-C1 = difference in concentration
Flux J
J = D/(kTfC) where f is the force per molecule, k is Boltzmann’s constant (R/No), R is the gas constant, N is the number of moles of the gas, T is the absolute temperature, C is concentration
