17 Heart Chapter

advertisement
Chapter 17
The Heart
Copyright © 2010 Pearson Education, Inc.
1
“Pressure”
Pressure
for Heart, Vessels, Lungs
Fluid—Material with no fixed shape (particles can easily move around each
other & flow in a direction)—Liquid or Gas
Pressure
Collective force of ALL impacts of ALL those fluid atoms &
molecules
Ratio of container size vs fluid amount
• Container:Fluid volume LARGE (BIG CONTAINER or little fluid):
Fewer particles hit wall → Low Pressure
• Container:Fluid volume small (small container or MUCH FLUID):
More particles hit any section of wall → High Pressure
Copyright © 2010 Pearson Education, Inc.
2
Pressure
Facts to know
As container shrinks (ex. Lungs
exhale), pressure rises. Fluid
is pushed (by all those particles on one side) away → Area of
lower pressure.
FLOW: HIGH pressure → LOW Pressure
Vice-versa if container expands
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
As fluid flows through tube, particles scrape wall.
Smaller tube = More wall to scrape
against = More Friction
“RESISTANCE” to flow
Copyright © 2010 Pearson Education, Inc.
Blood
(also a fluid)
3
Layers of the Heart Wall (see also lab)
Outer Pericardium: Superficial tough wrapping +
Serous Membrane & Pericardial cavity
1. Epicardium—Visceral layer of the serous
pericardium; Touches myocardium
--Outer layer of the heart wall proper
Copyright © 2010 Pearson Education, Inc.
4
Layers of the Heart Wall
2. Myocardium
A. Spiral bundles of cardiac muscle cells (cardiomyocytes)
B. Fibrous skeleton of the heart: crisscrossing layers of
connective tissue (collagens, laminin, fibronectin)
•
Anchors cardiac muscle fibers + Is pulled on
•
Supports large vessels & valves
•
Electrical Insulation: Restricts action potentials to
specific paths
3. Endocardium is continuous with endothelial lining of
blood vessels
Copyright © 2010 Pearson Education, Inc.
5
Pathway of Blood Through the Heart
Equal volumes of blood are pumped out each
ventricle (LV=RV stroke volume)
Pulmonary circuit -- Short, low-pressure circulation
Systemic circuit – Much resistance in the long
bodywide pathways
• LV beats against greater pressure
• More/Stronger muscle
→Different LV/RVentricle Anatomy
Copyright © 2010 Pearson Education, Inc.
6
Microscopic Anatomy of Cardiac Muscle
• Cardiac muscle cells are striated, short, branched,
& interconnected
• Connective tissue (endomysium) connects to the
fibrous skeleton
• T tubules are wide, but few. SR is simpler than in
skeletal muscle
• Many mitochondria (25–35% of cell volume)
• Able to use most fuel sources
(prefers fatty acids)
Copyright © 2010 Pearson Education, Inc.
7
Microscopic Anatomy of Cardiac Muscle
Intercalated discs: Folded border between cardiac
cells
Desmosomes prevent cells from separating during
contraction
Gap junctions
--Ions pass cell↔cell
→Electrically couple
adjacent cells
→Heart contracts
as a unit
→ Heart muscle functions as a ~syncytium
Copyright © 2010 Pearson Education, Inc.
8
Cardiac Muscle Contraction
Contraction
Much like skeletal muscle
Copyright © 2010 Pearson Education, Inc.
9
Cardiac Muscle Contraction
Much like skeletal muscle
Ca2+ increases in cytoplasm
↓
Binds to Troponin C (part of TN complex on actin filament)
↓
Actin & Myosin can touch. Also stops TN-I,
which inhibits myosin from hydrolyzing ATP.
↓
Myosin molecules “Walk” along actin →
Cell Contraction
Copyright © 2010 Pearson Education, Inc.
10
From Skeletal Muscle Chapter
Role of Ionic Calcium (Ca2+) in Contraction
LOW [Ca2+]I
• Tropomyosin blocks
the binding sites on
actin
• Myosin cross bridges
cannot attach to
binding sites on actin
Copyright © 2010 Pearson Education, Inc.
11
HIGH [Ca2+]I
• Additional Calcium
binds to Troponin
Copyright © 2010 Pearson Education, Inc.
12
Calcium-activated
Troponin undergoes
conformational change
Tropomyosin moves
away from actin’s
binding sites
Copyright © 2010 Pearson Education, Inc.
13
Myosin head can now
bind & cycle
This permits contraction
(sliding of the thin filaments by the
myosin cross bridges)
Heart Contraction Movie
Copyright © 2010 Pearson Education, Inc.
14
Cardiac Calcium
Skeletal muscle gets ~all Ca2+ needed from SR
Cardiac Muscle (Humans):
• 60-90% from Sarcoplasmic Reticulum (modified
Smooth ER)
• 10-40% from
Extracellular Fluid
Extracellular Ca2+ is necessary for SR Ca2+
release
Copyright © 2010 Pearson Education, Inc.
15
Cytosolic Ca2+ is proportional to Force
mmproduced
Usually: [Ca2+]I → Force
140
Systolic Force
2+
Systolic Cytosolic Ca
200
130
180
120
160
140
110
120
100
Peak Calcium (% 0.5 Hz)
Peak Developed Force (% 0.5 Hz)
220
100
.5
1
2
3
4
5
6
Frequency (Hz)
• Sometimes: Ca2+ Sensitivity → Force
Copyright © 2010 Pearson Education, Inc.
16
Cardiac Muscle Contraction—Action
Potential
1. Depolarization opens voltage-gated fast
Na+ channels in sarcolemma; then close
• –90 mV → +30 mV
then, some K+ channel open (starts downslope—BUT…)
2. Depolarization opens slower voltage-gated
Ca2+ channels in sarcolemma
--This incoming Ca2+ opens
ligand(Ca2+)-gated
Ca2+ channels on SR (next slide, step 2.5)
• Ca2+ surge(s) delay
repolarization (“plateau”)
Copyright © 2010 Pearson Education, Inc.
17
Cardiac Muscle Contraction
2.5. Ca2+ influx opens Ca2+-sensitive channels
on Sarcoplasmic Reticulum, which releases
stored Ca2+
• “Calcium-Induced Calcium Release”
• Also part of plateau
“E-C coupling” -- Ca2+ binds
to troponin & filaments slide
Copyright © 2010 Pearson Education, Inc.
18
Cardiac Contraction
1
Voltage-Gated
.
Na Channel
+
2
Voltage-Gated
.
Ca Channel
2+
Outside Cell
Ca2+
Ca2+
Inside Cell
Ca2+-gated
SR Ca2+
Channels
Na+
Binds to
TN-C
Ca2+
Ca2+
Na+
2.5
.
Sarcoplasmic
Reticulum
CONTRACTION
Released from
TN-C
RELAXATION
Copyright © 2010 Pearson Education, Inc.
From Greineder et al 2002
Duration of AP & contraction is longer in
cardiac than skeletal muscle (because of Ca
2+
)
plateau
VS.
Chapter 10
3. Repolarization:
a. Inactivation of Ca2+ channels
b. Removal of Ca2+ (outside & SR)
c. Opening of voltage-gated K+ channels
Copyright © 2010 Pearson Education, Inc.
20
Cardiac Repolarization
Voltage-Gated Ca2+
Ca2+ Channel
Outside Cell
3c
3b
3a
Inside Cell
Ca2+-gated
SR Ca2+
Channels
3a
Na+
Binds to
TN-C
Ca2+
Pump
Ca2+
Ca2+
NCX
K+ Channel
Na+
Ca2+
Sarcoplasmic
Reticulum
CONTRACTION
Released from
TN-C
RELAXATION
SERCA
3b
Copyright © 2010 Pearson Education, Inc.
From Greineder et al 2002
Relaxation
SR Ca2+ is pumped back into SR (SERCA on last slide)
Extracellular Ca2+ back out:
A. Na+/Ca2+ Exchanger (NCX on last slide)
B. (Tiny bit) Pumped back out (Sarcolemma Ca2+ pump)
Copyright © 2010 Pearson Education, Inc.
22
1 Depolarization is
2
Tension
development
(contraction)
3
1
Absolute
refractory
period
Time (ms)
Copyright © 2010 Pearson Education, Inc.
Tension (g)
Membrane potential (mV)
Action
potential
Plateau
due to Na+ influx through
fast voltage-gated Na+
channels. A positive
feedback cycle rapidly
opens many Na+
channels, reversing the
membrane potential.
Channel inactivation ends
this phase.
2 Plateau phase is
due to Ca2+ influx through
slow Ca2+ channels. This
keeps the cell depolarized
because few K+ channels
are open.
3 Repolarization is
due to Ca2+ channels
inactivating and K+
channels opening. This
allows K+ efflux, which
brings the membrane
potential back to its
resting voltage.
23
Force-Frequency Relationship (FFR)
As ↑HR , Cardiac Muscle contracts harder (↑”Contractility”)
(60-180 bpm; 1-3 Hz)
via Increased Ca2+ Transients
General Theory:
sticks to Calmodulin (Endocrine Chapter)
Activates: Ca2+/calmodulindependent protein kinase
mmmmm↓
Phosphorylates SERCA, SERCA’s
inhibitor, & Ca2+ channel
Systolic Force
2+
Systolic Cytosolic Ca
200
130
180
120
160
140
110
120
100
Peak Calcium (% 0.5 Hz)
Ca2+
140
220
Peak Developed Force (% 0.5 Hz)
↑ Frequency → Faster
Ca2+ Oscillations
mmmmm↓
100
.5
1
2
3
4
5
6
Frequency (Hz)
Flattens with most pathologies
→ More beat-to-beat Ca2+ (re)cycling
Copyright © 2010 Pearson Education, Inc.
24
Cardiac Muscle Contraction
Electrical
Depolarization is rhythmic &
spontaneous (Does not need nervous/endocrine input)
About 1% of cardiac cells are self-excitable
Long absolute refractory period (250 ms)
Copyright © 2010 Pearson Education, Inc.
25
Cardiac conduction system
A population of:
A. Noncontractile &
B. Autorhythmic
&
C. Networked
cells that initiate & distribute electrical impulses
to coordinate the depolarization and
contraction of the heart
Copyright © 2010 Pearson Education, Inc.
26
Autorhythmic (“Pacemaker-type”) Cells
1. Have unstable resting potentials (pacemaker potentials)
due to open slow HCN (~Na+) channels (Notice that the
membrane potential is never a flat line)
(Some K+ out, but Na+ in stronger).
2. At threshold (~-40mV), Ca2+ channels open.
Explosive Ca2+ influx →
Rapid AP upstroke
3. Repolarization
(a) Ca2+ channels Close
(b) Opening of
voltage-gated
K+ channels
Copyright © 2010 Pearson Education, Inc.
27
Sequence of Excitation
1. Sinoatrial (SA) node (“pacemaker”)
• Generates impulses ~60-75 times/minute
(“sinus rhythm”) @ default
• Depolarizes faster than any other part of the
myocardium (sets rate)
• Signal spreads through Atria,
via gap junctions & internodal
pathways
Copyright © 2010 Pearson Education, Inc.
28
Sequence of Excitation
2. Atrioventricular (AV) node
•
Smaller diameter fibers; fewer gap junctions
•
Delays impulses ~0.1 second for
atrial contraction & blood flow
•
Depolarizes ~45 times/minute
(in absence of SA node prodding)
Copyright © 2010 Pearson Education, Inc.
29
Sequence of Excitation
3. Atrioventricular (AV) bundle (“Bundle of His”)
• Only electrical connection through AV septum
(no other gap junctions here)
Copyright © 2010 Pearson Education, Inc.
30
Sequence of Excitation
4. Right & Left bundle branches
•
2 pathways in interventricular septum that
carry the impulses → Apex
Copyright © 2010 Pearson Education, Inc.
31
Sequence of Excitation
5. Purkinje fibers
•
Complete the pathway into the apex &
ventricular walls
•
Depolarize only ~20 times/minute
(in absence of AV node prodding)
Copyright © 2010 Pearson Education, Inc.
32
Superior vena cava
Right atrium
1 The sinoatrial (SA)
node (pacemaker)
generates impulses.
Internodal pathway
2 The impulses
pause (0.1 s) at the
atrioventricular
(AV) node.
3 The atrioventricular
(AV) bundle
connects the atria
to the ventricles.
4 The bundle branches
conduct the impulses
through the
interventricular septum.
5 The Purkinje fibers
Left atrium
Purkinje
fibers
Interventricular
septum
depolarize the contractile
cells of both ventricles.
(a) Anatomy of the intrinsic conduction system showing the
sequence of electrical excitation
Copyright © 2010 Pearson Education, Inc.
33
CCS Pathologies--Examples
Defects in the intrinsic conduction system may
result in:
1. Arrhythmias--Irregular heart rhythms
2. Asynchrony--Uncoordinated atrial &
ventricular contractions
3. Fibrillation--Rapid, irregular contractions;
useless for pumping blood
Copyright © 2010 Pearson Education, Inc.
34
Extrinsic Innervation of the Heart
Basal heartbeat is modified by the ANS
Cardiac centers in medulla oblongata
• Innervate SA and AV nodes, Heart muscle, &
Coronary arteries through
sympathetic neurons
• Inhibits SA & AV nodes
through parasympathetic
fibers in the vagus nerve
-- Normally DOMINANT
in heart
Copyright © 2010 Pearson Education, Inc.
35
The Cardiac Cycle
Cardiac
Cycle
Cardiac cycle: All events during one complete
heartbeat
• Systole—Contraction
• Diastole—Relaxation
Cycle Length-Duration of cycle, k(Heart Rate)
• 500 ms = 2 Hz = 120 bpm
Copyright © 2010 Pearson Education, Inc.
36
Phases of the Cardiac Cycle
1. Ventricular filling — Mid-to-late diastole
•
AV valves open. SL valves closed
•
80% of blood passively flows into ventricles
•
Atrial systole, for the remaining 20%
(Stops flow from veins. Final push into ventricles)
End diastolic volume (EDV): Volume of
blood in a ventricle at the end of
ventricular diastole
•
“Biggest size of ventricle”
(~120 ml)
Copyright © 2010 Pearson Education, Inc.
LA Pressure
LV Pressure
Phases of the Cardiac Cycle
2. Ventricular systole
•
Atria relax & ventricles begin to contract
•
Rising ventricular pressure closes AV valves
(a) Isovolumetric contraction phase (brief time as ventricle
contraction raises internal pressure; closing AV valves &
before SL valves open)
•
(b) Ejection phase--Ventricular
mmmpressure exceeds pressure in
mmmvessels, forcing SL valves
mmmopen
End systolic volume (ESV): Volume of
blood remaining in each ventricle
•
“Smallest size of ventricle”
(~50ml)
Copyright © 2010 Pearson Education, Inc.
Aorta Pressure
LA Pressure
LV Pressure
Phases of the Cardiac Cycle
3. Isovolumetric relaxation (early diastole)
•
Ventricles relax (→small vacuum)
•
Backflow of blood in aorta & pulmonary trunk
closes SL valves & causes dicrotic notch
(brief rise in aortic pressure)
•
AV valves still closed
•
Low pressure opens
AV valves.
Cycle starts over.
Copyright © 2010 Pearson Education, Inc.
39
Cardiac Output (CO)
Volume/
Rate
Volume of blood pumped by each ventricle in
1 minute
CO = heart rate (HR) x stroke volume (SV)
• HR = # beats per minute
• SV = Volume of blood pumped out by a
ventricle with each beat (SV = EDV – ESV)
Example: CO = 75 bpm x 70 ml = 5.25 L/min
Cardiac reserve: Difference between
resting ↔ maximal CO
Copyright © 2010 Pearson Education, Inc.
40
Regulation of Stroke Volume
SV = EDV – ESV
End Diastolic Volume –
End Systolic Volume
3 main factors affect SV
A. Preload (Venous return)
B. Contractility
C. Afterload
Copyright © 2010 Pearson Education, Inc.
{EDV}
{-} (Affects ESV)
{ESV}
41
A. Regulation of Stroke Volume {EDV}
Preload: Stretch of ventricular muscle cells before they
contract (“Frank-Starling Law of the heart”)
(Like Skeletal) Cardiac
muscle has a length-tension relationship
Cardiac muscle cells are usually shorter than optimal length
↑ Venous Return (More blood in heart at beat): Slow heartbeat +
Vasoconstriction & Skeletal Muscle help (Blood Vessel chapter)
• Increased venous return stretches the ventricles &
increases contraction force
Frank-Starling Law--Both:
This + Small Increased Ca2+ sensitivity
Copyright © 2010 Pearson Education, Inc.
Skeletal
Muscle
chapter
42
B. Regulation of Stroke Volume {-}
Contractility: Contractile strength at any muscle
length (independent of muscle stretch & EDV)
→ more blood pumped out
Increased Ca2+ influx (also sometimes can be filaments’ Ca
2+
sensitivity)
Positive inotropic agents increase contractility
• Norepinephrine & Epinephrine (neurotransmitter & hormones), Thyroid
hormone, Glucagon, drugs (ex. digitalis), ↑HR (not normally considered inotropic,
via FFR)
Negative inotropic agents decrease contractility
• Acidosis
• Increased extracellular K+
Isoproterenol-b-agonist
1 mN/mm
2
100 Fura-2 AU
• Calcium-reducing drugs
100 msec
Copyright © 2010 Pearson Education, Inc.
Systolic Force
Cyclopiazonic Acid-SERCA inhibitor
Systolic Calcium
43
Example
Contractility due to
Catecholamines
(ex. Epinephrine)
Copyright © 2010 Pearson Education, Inc.
44
C.
Regulation of Stroke Volume
{ESV}
Afterload: “push-back” Pressure that must be
overcome for ventricles to eject blood
Example: pressure in arteries
• Hypertension (high blood pressure due to resistance to
blood flow downstream of the heart) increases afterload
(heart must push harder)
→ Increased ESV and reduced SV (~can’t get it all out
during systole)
Copyright © 2010 Pearson Education, Inc.
45
Regulation of Heart Rate
+ Positive chronotropic factors ↑ heart rate
- Negative chronotropic factors ↓ heart rate
Copyright © 2010 Pearson Education, Inc.
46
Control
Autonomic Nervous System Regulation
Sympathetic nervous system is activated by
emotional or physical stress
Norepinephrine (& epinephrine) increases:
• Pacemaker firing rate (heart rate)
• Myocardial contractility (directly & indirectly, see
slide 45 and FFR)
CO = HR x SV
Copyright © 2010 Pearson Education, Inc.
47
Autonomic Nervous System Regulation
Parasympathetic nervous system slows HR
• Acetylcholine hyperpolarizes
pacemaker cells by opening
K+ channels
The heart at rest exhibits vagal tone
(parasympathetic)
--Rate lower than otherwise (100→75 bpm (slide 28)); no direct
48
mmeffect on contractility
Copyright © 2010 Pearson Education, Inc.
Chemical Regulation
1. Hormones
•
Epinephrine (adrenal medulla) raises HR &
Contractility
•
Thyroid Hormone increases HR &
Enhances the effects of NE and EPI
(Permissiveness)
2. Ion concentrations (ex. Ca2+ and K+)
maintained by other hormones (Kidney/Fluid
Chapters)
Copyright © 2010 Pearson Education, Inc.
49
Exercise (by
skeletal muscle and
respiratory pumps;
see Chapter 19)
Heart rate
(allows more
time for
ventricular
filling)
Bloodborne
epinephrine,
thyroxine,
excess Ca2+
Venous
return
Contractility
EDV
(preload)
ESV
Exercise,
fright, anxiety
Sympathetic
activity
Parasympathetic
activity
Heart
rate
Stroke
volume
Cardiac
output
Initial stimulus
Physiological response
Result
Copyright © 2010 Pearson Education, Inc.
50
Pathologies
Age-Related Changes Affecting the Heart
• Sclerosis & Thickening of Valve flaps
• Decline in cardiac reserve (ex. ↓FFR)
• Fibrosis of Myocardium
• Atherosclerosis (see blood vessel chapter)
• Stiffening of Aorta & other large arteries
Copyright © 2010 Pearson Education, Inc.
51
Pathologies
Angina pectoris
• Thoracic pain caused by fleeting deficiency of
blood to myocardium (ex. coronary artery
disease)
• Cells are weakened
• Often treated acutely with nitroglycerine (nitric
oxide precursor), which dilates arteries--including
coronary arteries
Copyright © 2010 Pearson Education, Inc.
52
Myocardial infarction (“heart attack”)
• Prolonged coronary blockage
• Areas of cell death are repaired with
noncontractile scar tissue (collagen) to reinforce
the now-weak area of the (usu. ventricular) wall
Copyright © 2010 Pearson Education, Inc.
53
Cardiac Hypertrophy (enlarging of cells)
2 types
1. Physiological—”Good” with exercise & pregnancy
(cardiomyocytes effects only)
2. Pathological—”Bad”-common in many cardiac diseases
Believed to be continuum:
1. Compensatory → 2. Decompensatory → 3. Heart Failure
Theory:
Result of “weak” heart
• “Real” Weakness—Infarction, Coronary atherosclerosis
• “Pseudo-Weakness”—Greater Resistance (ex. hypertension
Copyright © 2010 Pearson Education, Inc.
(afterload), stiff arteries)
1. “Compensatory”
• Cells enlarge for increased strength (but needing more O2, etc. +
feedback from original problem)
• ~~Advantageous molecular changes to ↑ force (ex. longer AP,
↓SERCA to increase Ca2+, slow Ca2+ fluxes)
• ↑ extracellular Collagen (strengthen walls over damaged areas)
2. “Decompensatory”
• Cells get longer, not thicker
• Collagen & other changes
become negative
→Lose cardiac reserve
3. Heart Failure:
Progressive condition where the CO is too low for blood
circulation to meet tissue needs
Copyright © 2010 Pearson Education, Inc.
55
Download
Random flashcards

Pastoralists

– Cards

Radioactivity

– Cards

Emergency medicine

– Cards

Create flashcards