Cardiovascular System:
The Heart
Heart Size,
Shape, Mass
• About the size of a
closed fist:
– 3.5” wide (at widest
pt) X 5” long. 2.5”
thick
• Cone-shaped: Base &
Apex
• 8 oz in adult females,
10 oz in adult males
Heart
Location
• In the mediastinum (tissue
between sternum &
vertebral column)
• 2/3 of its mass is left of
midline
• A cone lying on its side:
–
Base is toward your right shoulder,
apex points to your left hip
• Anterior surface - deep to
sternum
• Inferior surface – on
diaphragm
• Right border – against right
lung.
• Left border (pulmonary
border) – against left lung
Fibrous, Serous (Visceral & Parietal)
PERICARDIUM
Fibrous & Serous pericardium
• Pericardium – the sac that surrounds, protects, anchors
heart to diaphragm. It is composed of 2 layers - the
fibrous & serous (visceral & parietal layers) pericardium
The FIBROUS Pericardium
• FIBROUS PERICARDIUM
– Outermost layer
– Tough, inelastic, dense irregular CT
– Prevents overstretching of heart
– Anchors heart to diaphragm. Prevents rising of heart
The SEROUS PERICARDIUM
SEROUS pericardium: thinner,
delicate, inner layers that form a
fluid-filled sac. It has 2
continuous layers:
1. Parietal layer: is adhered
to fibrous pericardium
2. Visceral layer aka
“Epicardium”: is adhered
to heart
–
The pericardial cavity is
filled with Pericardial
fluid. The pericardial
cavity is the space
between parietal &
visceral layers.
–
The pericardial fluid
PREVENTS FRICTION
Systemic & Pulmonary Circulations
•
Two closed
circulatory
systems:
1. Body
2. Lungs
•
The output of one
becomes the input
of the other with
each beat of the
heart
Blood Flow
Within the
4 Heart
Chambers
FYI: is it just a pump?
Cardiac Output (CO)
• Total volume of blood in the body
is approximately 5L. CO is
typically about 5L/min
•
CO= Amount of blood pumped
by left or right ventricle PER
MINUTE
•
CO depends on Heart Rate &
Stroke Volume
1. HEART RATE ie number of beats
per minute. Normal is 75BPM
Heart pumps 5 L blood
PER MINUTE
2. STROKE VOLUME ie. the
amount of blood ejected from one
Ventricle PER BEAT. Normal is
70ml/beat in a 70 kg healthy man
ELECTRICAL ACTIVITY OF THE
HEART
Autorhythmic vs Contractile myocytes
• The Heart has 2 kinds of cells:
– Autorhythmic myocytes (purple circle / yellow cell) spontaneously
depolarize and generate action potentials
– Contractile myocytes (pink cells) contract together to pump blood as
the action potential spreads across them
The Sinoatrial (SA) Node or Pacemaker
• The SinoAtrial (SA) node is an area of modified cardiac
myocytes within the R atrium.
– Cells here spontaneously depolarize (become more positive) 100 x/min
a) Pacemaker potential: the spontaneous depolarization from -60 to
-35mV that precedes the action potential
b) Action potential: the depolarization that occurs after threshold of
-35 mV
Action Potential at the SA Node
1.
2.
3.
4.
SA node cells do not “rest”
Na+ channels spontaneously open at -60mV. Thus Na+ leaks into
SA node cells which initiates the pacemaker potential (If –funny
current)
Then Ca2+ enters the cell. 2nd part of pacemaker potential &
depolarizes cell to reach action potential
Finally, K+ exits cell which repolarizes the cell membrane to -60mV
Features of Cardiac Contractile Cells
•
•
•
•
•
•
•
•
Exhibit branching
Intercalated disks: at end of
each myocyte, its
sarcolemma thickens
– Stair-step appearance
– 2 disks are held together
by Desmosomes
Gap junctions connect
cytoplasm of adjoining cells
Striated/Sarcomeres: same
structure as skeletal muscle
cells: bands & zones of actin
&myosin, z-discs, m-lines
Sarcoplasmic reticulum:
smaller w less Ca2+ reserve
T-tubules: 1 per sarcomere.
located at the z-disk
Mitochondria: Larger, more
numerous (25% of cytosol)
One central nucleus:
cardiac myocytes are shorter
in length
Positive ions pass from SA to Contractile Cells through Gap Junctions
• Gap junction: a channel formed between two cells by 2 adjoined
connexons. Connects cytoplasm of 2 cells, allowing ions & small molecules
to pass through to adjoining cells quickly.
• Positive ions (Ca2+ & Na+) from autorhythmic cells enter the adjacent
contractile cells through gap junctions
Contractile Cell
Depolarization –
Fast Na Channels
1.
Gap Junction: Positive
ions (Na+ & Ca2+ enter
through gap junctions
which triggers:
2.
Rapid Depolarization:
Fast voltage-gated Na+
channels on the
sarcolemma open. The cell
instantly becomes positive
on the inside.
3.
Plateau Phase: at +20mV
Ca2+ & K+ channels open.
Influx and efflux of positive
ions is balanced so AP
graph plateaus.
Calcium-Triggered Calcium Release – plateau and contraction
•
Na+ & Ca2+ influx from an
adjacent cell changes
voltage (key) – NOT
NEUROTRANSMITTERS
•
Voltage-gated Ca channels
in T-tubules open & Ca
enters cell from ECF
•
Calcium-triggered
calcium release: Ca
entering cell binds to
ryanodine receptors, which
are Ca channels on the
sarcoplasmic reticulum
Sarcoplasmic Ca stores are
released into cell…
•
•
Ca binds to troponin,
tropomyosin moves off
myosin binding sites,
myosin binds to actin & the
sarcomeres shorten
Plateau, Contraction, Repolarization
• Ca2+ channels and K+
channels are open at the
same time.
• Ca2+ enters the cell,
while K+ leaves, creating
a plateau in the AP graph
• Ca2+ channels close,
while K+ channels remain
open – so the cell
becomes more negative
inside, or, repolarizes
cardiac excitation-contraction
coupling
Action potential vs contraction
• Action potential is generated first in the SA node,
• Then the action potential spreads to the contractile
myocytes.
• After the contractile myocytes depolarize, the
sarcomeres shorten and a contraction is generated.
Tetanus
• Unlike skeletal muscle,
cardiac muscle cannot
enter tetanus (sustained
contraction).
• The cardiac cell has a
refractory period that is
almost as long as the
entire muscle twitch
Sympathetic & Parasympathetic
HEART RATE REGULATION
Parasympathetic Vagus
Nerve (ACh) Slows HR
•
Parasympathetic Vagus nerve innervates SA & AV nodes and atrial myocardium. It
releases ACETYLCHOLINE which binds to muscarinic receptors on cardiac mm.
Binding of Ach & muscarinic receptors causes K+ to leave the cells so:
• SLOWS rate of depolarization of SA & AV nodes, thus HEART RATE DECREASES
• (Contractile Fibers: little effect on contractility because does not innervate ventricles)
• Vagus N. slows SA node to normal HR. Normal HR = 70-100 BPM.
Sympathetic Nerves (NE) Increase HR & Contractility
• Sympathetic “Cardiac Accelerator Nerves” innervate SA & AV nodes, and
most of the myocardium. They release NOREPINEPHRINE NT which binds
to β1 receptors. Binding of NE to β1 enhances Ca2+ entry to cell, thus, at:
– SA & AV nodes, it speeds rate of depolarization so HEART RATE INCREASES
– Contractile Fibers,more crossbridges form and CONTRACTILITY INCREASES
– 100-150 (simple tachycard), 150-200 (paroxysmal), 250-350 (flutter), 350+
(fibrillation)
Input for Heart Rate Regulation
• Input to the Cardiovascular Center in medulla oblongata comes from:
– Brain - cortex, limbic system (eg anxiety), hypothalamus
– Sensory Receptors - proprioceptors (limb position), chemoreceptors,
baroreceptors (artery & vein stretch, blood pressure changes)
Chemical & Other Regulation of HR
INCREASES HEART RATE
& CONTRACTILITY
– Hormones:
• Epinephrine
• Norepinephrine
• Thyroid hormones
– Cations:
•
Ca2+
– Other:
• Increased body
temperature (fever,
exercise)
TACHYCARDIA: increased
resting heart rate (>100bpm
for adult)
DECREASES HEART RATE &
CONTRACTILITY
– Cations:
• K+ blocks generation of
AP (Hyperkalemia)
• Na+ blocks Ca inflow
during AP
– Other:
• Decreased body
temperature
(hypothermia)
BRADYCARDIA: decreased
resting heart rate (<50bpm for
adult)
Damage to pacemaker,
or Ectopic pacemakers
produce Arrhythmias
THE CARDIAC CYCLE & EKG
Sequence Of Cardiac Conduction & Contraction
•
The Sinoatrial (SA) node
generates action potentials (AP)
•
AP propagates through walls of
both atria via gap junctions.
•
ATRIA CONTRACT
•
Atrioventricular (AV) node in
inter-atrial septum slows AP
conduction
•
AP can only pass from atria to
ventricles through AV bundle
(Bundle of His)
•
AP propagates down interventricular septum to apex via
Right and left bundle branches
•
Purkinje fibers conduct AP from
apex up walls of ventricles.
VENTRICLES CONTRACT.
•
ECG &
Cardiac
Cycle
• P- atrial depolarization
• QRS complex: Q- septal depolarization, R- early ventricular depolarization,
S- late ventricular depolarization
• T- ventricular repolarization
Cardiac Depolarization
Large P waves: enlargement of atria
Large R waves: enlarged ventricles
•
•
•
•
•
•
•
SA node: 60-100 bpm
Atrial cells: 55-60 bpm
AV node: 45-50 bpm
HIS bundle: 40-45 bpm
Bundle branch: 40-45 bpm
Purkinje cells: 35-40 bpm
Myocardial cells: 30-35 bpm
FYI: EKG leads
• Electrodes are placed on:
– arms & legs (limb leads: I, II,
III, AVR, AVL and AVF)
– 6 positions on chest (chest
leads: V1, V2, V3, V4, V5, V6).
• limb leads provide views of
cardiac activity in frontal plane
• chest leads provide views in
horizontal plane
• 12 different tracings are
produced
• Can tell:
1.
2.
3.
4.
Abnormal conducting pathway
Enlarged heart
Damaged regions of heart
Cause of chest pain
Normal Lead II Tracing
•
movement of charges (ions)
generate an electrical current
•
electrical currents from cardiac
action potentials can be detected
on the surface of the body
•
Electrocardiogram: recording of
electrical signals.
Electrocardiograph: instrument used
•
Cardiac Cycle = one heartbeat
• Systole=
Contraction
• Diastole =
Relaxation
• Cardiac cycle = one
heartbeat:
– systole & diastole
of atria
+
– systole & diastole
of ventricles
Cardiac Cycle
S2
S1
1) START: Passive ventricular filling. 80% of the ventricle fills at rest, or DIASTOLE. Approximately 105mL.
2) Atria contract & pump 25mL (20%) more into ventricles so the End Diastolic Volume is about 130mL.
3) QRS - ventricular DEPOLARIZATION.
4) Isovolumetric Ventricular contraction - AV valves shut (ventricles are exerting force but not shortening)
5) Ventricular ejection or SYSTOLE. SL valves open as ventricular pressure exceeds aortic/pulmonary pressure
6) 70mL ejected into aorta & pulm trunk. Volume remaining in each ventricle(~60mL) is End Systolic Volume
Closing Valves Produce Heart Sounds – S1 & S2
HEART VALVES
4 Heart Valves: 4 Fibrous rings (valve
annuli)
• 4 Dense connective tissue rings surround
the valves & are fused together. Creates an electrical barrier.
Electrical insulation. Prevents valve overstretching
Fibrous Skeleton Of The Heart
•
•
•
•
*Rings prevent valve overstretching
*Act as electrical insulation between atria & ventricles
Insertion points for cardiac muscle fibers
The 4 rings merge with the interventricular septum
Heart Valves: 2 AV & 2 Semilunar valves
• When the 2 atria contract: AV or atrioventricular valves (tricuspid +
mitral) valves open
• When 2 ventricles contract: Semilunar (aortic+ pulmonic)valves open
Atrioventricular or “AV” Valves, S1
• AV valves: TRICUSPID & BICUSPID VALVES
• When AV valves are Open, during ventricular filling:
– Atria are pumping blood into ventricles
– Valve cusps project into ventricle
– Chordae tendinae are slack & papillary muscles relaxed
• When AV valves are Closed, during ventricular contraction, S1:
•
– AV cusps meet & close
– chordae tendinae are taught & papillary muscles contracted
**AV valves prevent backflow of blood to atria when ventricles are contracting
Chordae tendinae & papillary
muscles of AV valves
• Structures on Mitral & tricuspid valves only
• When atria contract, chordae tendinae are slack, hanging threads of
connective tissue
• When ventricles contract, blood pushes up against bottom of valve leaflets
causing them to close & balloon up, like a parachute.
• Papillary muscles contract, pulling on chordae tendinae to keep valve closed
Semilunar (SL) Valves, S2
• Semilunar Valves = AORTIC
& PULMONARY VALVES
• SL valves open when
pressure in the ventricles
exceeds pressure of blood
sitting in the arteries
• SL valves close when
ventricles relax.
• This creates the heart
sound – S2
• Prevent backflow of blood
from arteries into ventricles
Heart Sounds: S1, S2
• Auscultation – listening to
sounds within the body
• First sound, S1, “lubb” is
louder, longer
– AV valves close due to
– VENTRICULAR SYSTOLE /
contraction
• Second sound, S2, “dupp”
is shorter, not as loud
– Semilunar valves close
due to
– VENTRICULAR DIASTOLE /
relaxation
Preload, Contractility, Afterload
STROKE VOLUME
Stroke Volume (think “Beat volume”)
Stroke volume depends on:
1. PRELOAD - volume of blood in the
ventricle before it contracts (ie end
diastolic volume)
•
Frank-Starling law: increased
venous return = increased stroke
volume (because more ventricular
stretch= greater contraction)
2. CONTRACTILITY (Inotropy) –
muscular strength of the contraction
•
•
Positive inotropic agents  Ca2+
thus  # of cross bridges &  force of
contraction: Ca, Epi, NE
Negative inotropic agents- # of
cross bridges,  force of contraction:
Ca channel blockers, ß-blockers
3. AFTERLOAD – the pressure
behind the semilunar valves that
must be exceeded for blood to be
ejected from ventricles (ie mean
arterial pressure)
Blood flow and oxygen supply to the heart muscle
CORONARY (CARDIAC)
CIRCULATION
Coronary (Cardiac) Circulation
• The myocardium
(heart muscle) has
its own blood supply,
the coronary, or
cardiac, circulation
Right Coronary Artery
supplies Right & Back
of heart
Right coronary artery
supplies:
–
R atrium via Atrial
branches
–
R ventricle, Lateral side
via Right marginal
branch
–
Posterior walls of 2
ventricles via Posterior
interventricular
branch
Coronary Veins
• Coronary Sinus – a
large vessel on
posterior surface of the
heart
– Drains all deoxygentated
myocardium blood into
R atrium
– Collects blood from
• Great (front), Middle
(back), Small (R) &
Anterior (R) cardiac
veins
Cardiac Circulation
• 2 Coronary arteries (R & L
coronary aa) branch off
from the ascending aorta
• When ventricles contract,
coronary arteries are
squeezed shut
• When ventricles relax,
blood from the aorta
rushes into the coronary
arteries, oxygenating the
myocardium
ATP synthesis
•
ATP production in cardiac myocytes
is mostly made by AEROBIC
cellular respiration in cardiac
mitochondria
•
Aerobic ATP synthesis requires
oxygen for oxidative phosphorylation
of ADP to ATP
•
O2 is supplied by myoglobin in
cardiac cells or hemoglobin from
cardiac circulation
•
Some ATP is produced from
creatine phosphate
– If creatine kinase (CK-MB) is
found in blood (leaked from
damaged cells) it’s a sign of
myocardial infarction
Fuels for ATP production in Cardiac Myocytes
– Fuels at rest:
• 60% fatty acids
• 35% glucose
– Fuels during exercise:
• Above fuels +
• Amino acids, ketone bodies & lactic acid from skeletal muscle
Coronary artery disease
• Myocardial Ischemia: narrowed artery reduces blood/ oxygen
supply (hypoxia), weakening myocardium & producing squeezing
pain (angina pectoris)
• Myocardial Infarction: blocked artery, complete obstruction of
blood flow to myocardium resulting in distal tissue death
Angiogram, angioplasty, stent
Reperfusion
Damage
• “Reperfusion” =
reestablishing blood flow
to myocardium after
blockage of a coronary
artery
• Reperfusion damages
heart tissue further due to
formation of oxygen free
radicals from reintroduced
oxygen, and Ca2+, and
activation of the immune
system
• Antioxidants like
glutathione peroxidase,
Catalase can mitigate the
effects.
Stenosis & Insufficiency
HEART VALVE DISORDERS
Heart Valve Disorders: Stenosis
• Age-related Aortic
stenosis is most
common type
• Mitral Valve Stenosis
is most commonly due
to Rheumatic fever. 2-3
wks after strep infxn antibodies inflame the
CT of joints, heart
valves (usually mitral)
and other organs.
Heart Valve disorders: Insufficiency
• Valve Insufficiency / incompetence – failure to
close fully leads to backflow of blood (regurgitation).
May be due to HTN, post-infection…
Hear Valve Disorders: Stenosis
• Stenosis (narrowing) – valve leaflets thicken, stiffen, or fuse together
so it cannot fully open.
• May be due to calcification, post-inflammation, scar formation,
tumors, congenital
• Age-related Aortic Stenosis from calcification is most common type
Heart Valve Disorders:
Insufficiency w Regurgitation
Most common valves
affected:
• Mitral insufficiency –
backflow of blood from
L ventricle to L atrium
– Mitral valve prolapse
(MVP) – one or both
valve cusps protrude
into L atrium during
ventricular contraction
• Aortic insufficiency –
backflow of blood from
aorta into L ventricle
Congestive Heart Failure
• In CHF, the heart is a failing pump:
• Stroke Volume decreases, blood
remains in ventricle (end systolic
volume increases)
• End diastolic volume increases
gradually (ventricle enlarges)
– If Left ventricle fails first,blood
backs up into lungs, get Pulmonary
edema
– If Right ventricle fails first, blood
backs up in body, get Peripheral
edema
• CHF may be due to: coronary
artery disease, congenital defects,
long-term high blood pressure
(increases afterload), myocardial
infarctions, valve disorders.