Lec 12 - Pressure, Volume, Flow, and Resistance and Cardiac Muscle and the Heart

How does the heart create pressure?

Its contraction creates pressure without changing the volume of blood; blood leaving the heart into vessels is driven by driving pressure

Effect of vessel dilation vs constriction on blood pressure?

Dilation decreases blood pressure; constriction increases blood pressure

Do volume changes affect blood pressure?

Yes, volume changes affect blood pressure in the cardiovascular system

In which direction does blood flow?

From higher pressure to lower pressure

Flow and pressure gradient?

Flow through a tube is directly proportional to the pressure gradient (Flow ~ deltaP); the higher the gradient, the greater the flow

Fig 14.2: Mean blood pressure in the systemic circulation?

High of about 93 mm Hg in the aorta, falling through arteries, arterioles, capillaries, venules, veins to a low of a few mm Hg in the venae cavae

Flow and resistance?

Flow is inversely proportional to resistance (Flow ~ 1/R); flow decreases as resistance increases

Poiseuille's law?

R = 8L(eta)/(pi r^4), i.e., R ~ L(eta)/r^4

Resistance and tube length?

Proportional to length (L); resistance increases as length increases

Resistance and viscosity?

Proportional to viscosity (eta), the thickness of the fluid (blood); increases as viscosity increases

Resistance and radius?

Inversely proportional to radius to the fourth power (R ~ 1/r^4); resistance decreases as radius increases (vasoconstriction vs vasodilation)

Flow formula combining pressure and resistance?

Flow ~ deltaP / R; flow increases as the pressure gradient increases or as resistance decreases

Fig 14.3e: Effect of radius on resistance and flow?

As radius decreases, resistance increases (R ~ 1/r^4). Tube A radius 1: R = 1, flow = 1. Tube B radius 2: R = 1/16, flow = 16

Flow rate?

The volume of blood that passes a given point in the system per unit time (what 'flow' usually means)

Velocity of flow?

Distance a fixed volume of blood travels in a given period of time; v = Q/A (Q = flow rate, A = cross-sectional area)

Mean arterial pressure (MAP)?

Primary driving force for blood flow; pressure maintained in the arteries during heart relaxation; MAP ~ cardiac output (CO) x peripheral resistance (PR)

How many chambers does the heart have?

Four

What is the heart mostly made of?

Myocardium, encased in pericardium

Atria vs ventricles?

Paired atria are thin-walled upper chambers; paired ventricles are thick-walled lower chambers

Which vessels carry blood from the heart?

Aorta and pulmonary trunk

Which vessels return blood to the heart?

Vena cava and pulmonary veins

Deoxygenated blood path?

Vena cava > right atrium > right ventricle > pulmonary trunk

Oxygenated blood path?

Pulmonary veins > left atrium > left ventricle > aorta

Connective tissue rings of the heart?

Serve as origin and insertion for cardiac muscles

Fig 14.5a: Location of the heart?

In the center of the thorax; labeled sternum, base of heart, apex of heart, diaphragm, position of semilunar valves and AV valves

Fig 14.5b: Color coding?

Vessels carrying well-oxygenated blood are red; those with less well-oxygenated blood are blue (heart, aorta, vena cava)

Fig 14.5d: Superior view of transverse plane?

Labels: bronchus, superior vena cava, esophagus, aorta (segment removed), pulmonary artery, pulmonary vein, right atrium, right ventricle, pericardium, sternum, pericardial cavity, left ventricle, left atrium

Fig 14.5e: Pericardium?

Heart is encased within a membranous fluid-filled sac, the pericardium (diaphragm below)

Fig 14.5f: Ventricles and vessels?

Ventricles occupy the bulk of the heart; arteries and veins all attach to the base. Labeled: aorta, pulmonary artery, superior vena cava, right atrium, auricle of left atrium, coronary artery and vein, right and left ventricle

Fig 14.5g: What ensures one-way flow?

Two sets of valves (pulmonary semilunar, aortic semilunar, left AV/bicuspid cusp, right AV/tricuspid cusp); also chordae tendineae, papillary muscles, septum, descending aorta

Fig 14.5h: Myocardial muscle cells?

Branched, have a single nucleus, attached to each other by specialized junctions known as intercalated disks

Table 14.2: Right atrium?

Receives blood from venae cavae; sends to right ventricle (low oxygen)

Table 14.2: Right ventricle?

Receives from right atrium; sends to lungs (low oxygen)

Table 14.2: Left atrium?

Receives from pulmonary veins; sends to left ventricle (well oxygenated)

Table 14.2: Left ventricle?

Receives from left atrium; sends to body except lungs (well oxygenated)

Table 14.2: Venae cavae?

Receive from systemic veins; send to right atrium

Table 14.2: Pulmonary trunk (artery)?

Receives from right ventricle; sends to lungs

Table 14.2: Pulmonary vein?

Receives from veins of the lungs; sends to left atrium

Table 14.2: Aorta?

Receives from left ventricle; sends to systemic arteries

Table 14.2 color code?

Blue = lower oxygen content; red = well-oxygenated blood

Atrioventricular (AV) valves?

Between atria and ventricles

Chordae tendineae?

Prevent eversion of AV valves during ventricular contraction; attached to valve flaps from papillary muscles

Right vs left AV valve?

Tricuspid valve on the right; bicuspid (mitral) valve on the left

Semilunar valves?

Between ventricles and arteries: aortic valve and pulmonary valve

Coronary circulation?

Supplies blood to the heart; coronary arteries vs coronary veins

Fig 14.7a-b: Ventricular contraction?

AV valves remain closed to prevent backflow into atria; aortic and pulmonary semilunar valves open; chordae tendineae and papillary muscles tense; left ventricle contracted. Fibrous skeleton labeled

Fig 14.7c-d: Ventricular relaxation?

Semilunar valves close and prevent blood that entered the arteries from flowing back into the ventricles; mitral (bicuspid) valve open; chordae tendineae and papillary muscles relaxed; left ventricle dilated

Fig 14.8: Coronary vessels labeled?

Right coronary artery (RCA), left coronary artery (LCA), circumflex branch of LCA, anterior interventricular branch of LCA (LAD), posterior interventricular branch of RCA, great cardiac vein, middle cardiac vein, small cardiac vein, coronary sinus

Autorhythmic cells (pacemakers)?

Signal for contraction; smaller, with fewer contractile fibers than contractile cells; no organized sarcomeres

Contractile cells?

Striated fibers organized into sarcomeres

Cardiac vs skeletal muscle (6 differences)?

1) Smaller, single nucleus. 2) Branch and join neighbors via intercalated disks. 3) Gap junctions. 4) T-tubules larger and branch. 5) SR smaller. 6) Mitochondria occupy one-third of cell volume

Fig 14.9a: Ventricular muscle arrangement?

Spiral arrangement allows contraction to squeeze blood upward from the apex

Fig 14.9b: Intercalated disks?

Contain desmosomes that transfer force from cell to cell and gap junctions that let electrical signals pass rapidly from cell to cell

Cardiac EC coupling: where does the action potential start?

With the heart pacemaker cells

Ca2+-induced Ca2+ release (CICR)?

Voltage-gated L-type Ca2+ channels in the cell membrane open; ryanodine receptors (RyR) in the SR open in response to Ca2+ inflow

Ca2+ spark?

Local release of Ca2+ through RyR; summed sparks create a Ca2+ signal

L-type channel = ?

Dihydropyridine-sensitive L-type voltage-gated calcium channel = DHPR

After the Ca2+ signal in cardiac muscle?

Ca2+ binds troponin; crossbridge cycle as in skeletal muscle

Cardiac relaxation: how is Ca2+ removed?

Into the SR with Ca2+-ATPase; out of the cell through the Na+-Ca2+ exchanger (NCX)

Fig 14.10 steps 1-5?

1) Action potential enters from adjacent cell. 2) Voltage-gated Ca2+ channels open; Ca2+ enters. 3) Ca2+ induces Ca2+ release through RyR. 4) Local release causes Ca2+ spark. 5) Summed sparks create a Ca2+ signal

Fig 14.10 steps 6-10?

6) Ca2+ binds troponin to start contraction. 7) Relaxation when Ca2+ unbinds. 8) Ca2+ pumped back into SR for storage. 9) Ca2+ exchanged with Na+ by NCX antiporter. 10) Na+ gradient maintained by Na+-K+-ATPase (3 Na+ out, 2 K+ in)

Can cardiac contraction be graded?

Yes; force is proportional to the number of active crossbridges, determined by how much Ca2+ is bound to troponin; sarcomere length also affects force

Fig 14.11: Phase 0 channels?

Na+ channels open

Fig 14.11: Phase 1 channels?

Na+ channels close

Fig 14.11: Phase 2 channels?

Ca2+ channels open; fast K+ channels close

Fig 14.11: Phase 3 channels?

Ca2+ channels close; slow K+ channels open

Fig 14.11: Phase 4?

Resting potential (phase numbers are a convention)

Fig 14.12a: Cardiac refractory period?

Lasts almost as long as the entire muscle twitch (about 250 msec from -90 mV baseline)

Fig 14.12b: Long refractory period?

Prevents tetanus in cardiac muscle (no summation)

Contractile cell phase 4?

Resting membrane potential

Contractile cell phase 0?

Depolarization due to Na+ inflow

Contractile cell phase 1?

Initial repolarization; Na+ channels close

Contractile cell phase 2?

Plateau; long action potential due to Ca2+ inflow; sustains refractory period and prevents tetanus

Contractile cell phase 3?

Rapid repolarization due to K+ outflow

Autorhythmic cells: membrane potential?

Unstable; called pacemaker potential

Autorhythmic cells: initial depolarization?

Due to open If channels > Na+ inflow

Autorhythmic cells: then?

Depolarization opens voltage-gated Ca2+ channels > Ca2+ inflow; If channels close > decreased Na+ inflow

Autorhythmic cells: at threshold?

A 2nd type of voltage-gated Ca2+ channel opens > steep depolarization

Autorhythmic cells: at peak?

Ca2+ channels have closed; slow K+ channels open > decreased Ca2+ inflow and increased K+ movement; pacemaker potential returns to lowest point

Fig 14.13: Pacemaker potential values?

Gradually becomes less negative from about -60 mV to threshold at about -40 mV, triggering an action potential (peak about +20 mV)

Fig 14.13: Ion movements?

Net Na+ in (pacemaker potential); Ca2+ in (rising phase); K+ out (falling phase)

Fig 14.13c: Channel states?

-60 mV: If channels open. Near threshold: some Ca2+ channels open, If channels close. Rising phase: lots of Ca2+ channels open. Peak: Ca2+ channels close, K+ channels open. Minimum: K+ channels close, If channels open

Table 14.3: Membrane potential?

Skeletal: stable at -70 to -80 mV. Contractile myocardium: stable at -90 mV. Autorhythmic: unstable pacemaker potential, usually starts at -60 mV

Table 14.3: Events leading to threshold?

Skeletal: net Na+ entry through ACh-operated channels. Contractile: depolarization enters via gap junctions. Autorhythmic: net Na+ entry through If channels, reinforced by Ca2+ entry

Table 14.3: Rising phase?

Skeletal: Na+ entry. Contractile: Na+ entry. Autorhythmic: Ca2+ entry

Table 14.3: Repolarization?

Skeletal: rapid, K+ efflux. Contractile: extended plateau from Ca2+ entry; rapid phase caused by K+ efflux (slide text says Na+ efflux; Phase 3 slide says K+ outflow). Autorhythmic: rapid, K+ efflux

Table 14.3: Hyperpolarization?

Skeletal: due to excessive K+ efflux at high K+ permeability; when K+ channels close, leak of K+ and Na+ restores resting state. Contractile: none; resting potential -90 mV is the K+ equilibrium potential. Autorhythmic: normally none; when repolarization hits -60 mV, If channels open again; ACh can hyperpolarize the cell

Table 14.3: Duration of action potential?

Skeletal: short, 1-2 msec. Contractile: extended, 200+ msec. Autorhythmic: variable, generally 150+ msec

Table 14.3: Refractory period?

Skeletal: generally brief. Contractile: long, because resetting of Na+ channel gates is delayed until end of action potential. Autorhythmic: not significant in normal function

Learning outcomes (part 1)?

Describe functions of the cardiovascular system with examples; describe organization of the cardiovascular system starting and ending in the aorta; define and explain relationships among pressure, hydrostatic pressure, pressure gradients, flow, velocity of flow, resistance and radius

Learning outcomes (part 2)?

Describe internal and external heart anatomy; describe the two types of myocardial cells and their arrangement; describe membrane proteins and ion movement in myocardial EC coupling and relaxation; compare and contrast action potentials of autorhythmic and contractile cells

Key words (circulation and flow)?

atrium, ventricle, pulmonary arteries, pulmonary veins, pulmonary circulation, aorta, capillaries, superior vena cava, inferior vena cava, systemic circulation, portal system, hepatic portal system, hydrostatic pressure, resistance (R), viscosity (eta), Poiseuille's law, vasoconstriction, vasodilation, flow rate, velocity of flow, mean arterial pressure (MAP), cardiac output, peripheral resistance

Key words (heart and cardiac muscle)?

apex, base, pericardium, myocardium, pulmonary trunk, atrioventricular (AV) valves, semilunar valves, chordae tendineae, papillary muscles, tricuspid valve, bicuspid valve, mitral valve, aortic valve, pulmonary valve, myogenic, autorhythmic cells, pacemakers, intercalated disks, desmosomes, gap junctions, voltage-gated L-type Ca2+ channels, ryanodine receptor Ca2+ release channels (RyR), Ca2+-induced Ca2+ release (CICR), Na+-Ca2+ exchanger, If channels, graded contractions