Chapter 18
The Cardiovascular System: The Heart:
Part A

The Pulmonary and Systemic Circuits
•	Heart is transport system; two 
side-by-side pumps
–	Right side receives oxygen-poor blood from tissues
•	Pumps to lungs to get rid of CO2, pick up O2, via pulmonary circuit
–	Left side receives oxygenated blood from lungs
•	Pumps to body tissues via systemic circuit

The Pulmonary and Systemic Circuits
•	Receiving chambers of heart:
–	Right atrium
•	Receives blood returning from systemic circuit
–	Left atrium
•	Receives blood returning from pulmonary circuit

The Pulmonary and Systemic Circuits
•	Pumping chambers of heart:
–	Right ventricle
•	Pumps blood through pulmonary circuit
–	Left ventricle
•	Pumps blood through systemic circuit

Heart Anatomy
•	Approximately size of fist
•	Location:
–	In mediastinum between second rib and fifth intercostal space
–	On superior surface of diaphragm
–	Two-thirds of heart to left of midsternal line
–	Anterior to vertebral column, posterior to sternum

Heart Anatomy
•	Base (posterior surface) leans toward right shoulder
•	Apex points toward left hip
•	Apical impulse palpated between fifth and sixth ribs, just below left nipple

Coverings of the Heart: Pericardium
•	Double-walled sac
•	Superficial fibrous pericardium
–	Protects, anchors to surrounding structures, and prevents overfilling

Pericardium
•	Deep two-layered serous pericardium
–	Parietal layer lines internal surface of fibrous pericardium
–	Visceral layer (epicardium) on external surface of heart
–	Two layers separated by fluid-filled pericardial cavity (decreases friction)

Homeostatic Imbalance
•	Pericarditis
–	Inflammation of pericardium
–	Roughens membrane surfaces  pericardial friction rub (creaking sound) heard with stethoscope
–	Cardiac tamponade
•	Excess fluid sometimes compresses heart  limited pumping ability

Layers of the Heart Wall
•	Three layers of heart wall:
–	Epicardium
–	Myocardium
–	Endocardium

•	Epicardium
–	Visceral layer of serous pericardium

Layers of the Heart Wall
•	Myocardium 
–	Spiral bundles of contractile cardiac muscle cells 
–	Cardiac skeleton: crisscrossing, interlacing layer of connective tissue
•	Anchors cardiac muscle fibers 
•	Supports great vessels and valves
•	Limits spread of action potentials to specific paths

Layers of the Heart Wall
•	Endocardium continuous with endothelial lining of blood vessels
–	Lines heart chambers; covers cardiac skeleton of valves

Chambers 
•	Four chambers:
–	Two superior atria
–	Two inferior ventricles
•	Interatrial septum – separates atria
–	Fossa ovalis – remnant of foramen ovale of fetal heart
•	Interventricular septum – separates ventricles

Chambers and Associated Great Vessels
•	Coronary sulcus (atrioventricular groove)
–	Encircles junction of atria and ventricles
•	Anterior interventricular sulcus
–	Anterior position of interventricular septum
•	Posterior interventricular sulcus
–	Landmark on posteroinferior surface 

Atria: The Receiving Chambers
•	Auricles
–	Appendages that increase atrial volume
•	Right atrium
–	Pectinate muscles
–	Posterior and anterior regions separated by crista terminalis
•	Left atrium
–	Pectinate muscles only in auricles

Atria: The Receiving Chambers
•	Small, thin-walled
•	Contribute little to propulsion of blood
•	Three veins empty into right atrium:
–	Superior vena cava, inferior vena cava, coronary sinus
•	Four pulmonary veins empty into left atrium

Ventricles: The Discharging Chambers 
•	Most of the volume of heart
•	Right ventricle - most of anterior surface
•	Left ventricle – posteroinferior surface
•	Trabeculae carneae – irregular ridges of muscle on walls
•	Papillary muscles – anchor chordae tendineae

Ventricles: The Discharging Chambers 
•	Thicker walls than atria
•	Actual pumps of heart
•	Right ventricle 
–	Pumps blood into pulmonary trunk
•	Left ventricle	
–	Pumps blood into aorta (largest artery in body)

Heart Valves
•	Ensure unidirectional blood flow through heart
•	Open and close in response to pressure changes
•	Two atrioventricular (AV) valves
–	Prevent backflow into atria when ventricles contract
–	Tricuspid valve (right AV valve)
–	Mitral valve (left AV valve, bicuspid valve)
–	Chordae tendineae anchor cusps to papillary muscles
•	Hold valve flaps in closed position

Heart Valves
•	Two semilunar (SL) valves
–	Prevent backflow into ventricles when ventricles relax
–	Open and close in response to pressure changes
–	Aortic semilunar valve
–	Pulmonary semilunar valve

Homeostatic Imbalance
•	Two conditions severely weaken heart:
–	Incompetent valve
•	Blood backflows so heart repumps same blood over and over
–	Valvular stenosis
•	Stiff flaps – constrict opening  heart must exert more force to pump blood
•	Valve replaced with mechanical, animal, or cadaver valve

Pathway of Blood Through the Heart
•	Pulmonary circuit
–	Right atrium  tricuspid valve  right ventricle
–	Right ventricle  pulmonary semilunar valve  pulmonary trunk  pulmonary arteries  lungs
–	Lungs  pulmonary veins  left atrium

Pathway of Blood Through the Heart
•	Systemic circuit
–	Left atrium  mitral valve  left ventricle
–	Left ventricle  aortic semilunar valve  aorta
–	Aorta  systemic circulation

Pathway of Blood Through the Heart
•	Equal volumes of blood pumped to pulmonary and systemic circuits
•	Pulmonary circuit short, low-pressure circulation
•	Systemic circuit long, high-friction circulation
•	Anatomy of ventricles reflects differences
–	Left ventricle walls 3X thicker than right
•	Pumps with greater pressure

Coronary Circulation
•	Functional blood supply to heart muscle itself
–	Delivered when heart relaxed
–	Left ventricle receives most blood supply
•	Arterial supply varies among individuals
•	Contains many anastomoses (junctions)
–	Provide additional routes for blood delivery
–	Cannot compensate for coronary artery occlusion

Coronary Circulation: Arteries
•	Arteries arise from base of aorta
•	Left coronary artery branches  anterior  interventricular artery and circumflex artery
–	Supplies interventricular septum, anterior ventricular walls, left atrium, and posterior wall of left ventricle
•	Right coronary artery branches  right marginal artery and posterior interventricular artery
–	Supplies right atrium and most of right ventricle

Coronary Circulation: Veins
•	Cardiac veins collect blood from capillary beds
•	Coronary sinus empties into right atrium; formed by merging cardiac veins
–	Great cardiac vein of anterior interventricular sulcus
–	Middle cardiac vein in posterior interventricular sulcus
–	Small cardiac vein from inferior margin
•	Several anterior cardiac veins empty directly into right atrium anteriorly

Homeostatic Imbalances
•	Angina pectoris
–	Thoracic pain caused by fleeting deficiency in blood delivery to myocardium
–	Cells weakened
•	Myocardial infarction (heart attack)
–	Prolonged coronary blockage
–	Areas of cell death repaired with noncontractile scar tissue

Microscopic Anatomy of Cardiac Muscle
•	Cardiac muscle cells striated, short, branched, fat, interconnected, 1 (perhaps 2) central nuclei
•	Connective tissue matrix (endomysium) connects to cardiac skeleton
–	Contains numerous capillaries
•	T tubules wide, less numerous; SR simpler than in skeletal muscle
•	Numerous large mitochondria (25–35% of cell volume)

Microscopic Anatomy of Cardiac Muscle
•	Intercalated discs - junctions between cells - anchor cardiac cells 
–	Desmosomes prevent cells from separating during contraction
–	Gap junctions allow ions to pass from cell to cell; electrically couple adjacent cells
•	Allows heart to be functional syncytium
–	Behaves as single coordinated unit

Chapter 18
The Cardiovascular System: The Heart:
Part B

Cardiac Muscle Contraction
•	Three differences from skeletal muscle:
–	~1% of cells have automaticity (autorhythmicity)
•	Do not need nervous system stimulation
•	Can depolarize entire heart
–	All cardiomyocytes contract as unit, or none do
–	Long absolute refractory period (250 ms)
•	Prevents tetanic contractions

Cardiac Muscle Contraction
•	Three similarities with skeletal muscle:
–	Depolarization opens few voltage-gated fast Na+ channels in sarcolemma 
•	Reversal of membrane potential from –90 mV to +30 mV
•	Brief; Na channels close rapidly
–	Depolarization wave down T tubules  SR to release Ca2+ 
–	Excitation-contraction coupling occurs
•	Ca2+ binds troponin  filaments slide

Cardiac Muscle Contraction
•	More differences
–	Depolarization wave also opens slow Ca2+ channels in sarcolemma  SR to release its Ca2+ 
–	Ca2+ surge prolongs the depolarization phase (plateau)

Cardiac Muscle Contraction
•	More differences
–	Action potential and contractile phase last much longer
•	Allow blood ejection from heart
–	Repolarization result of inactivation of Ca2+ channels and opening of voltage-gated K+ channels
•	Ca2+ pumped back to SR and extracellularly

Energy Requirements
•	Cardiac muscle
–	Has many mitochondria
•	Great dependence on aerobic respiration
•	Little anaerobic respiration ability
–	Readily switches fuel source for respiration
•	Even uses lactic acid from skeletal muscles

Homeostatic Imbalance
•	Ischemic cells  anaerobic respiration  lactic acid 
–	High H+ concentration  high Ca2+ concentration 
•	 Mitochondrial damage  decreased ATP production
•	 Gap junctions close  fatal arrhythmias

Heart Physiology: Electrical Events
•	Heart depolarizes and contracts without nervous system stimulation
–	Rhythm can be altered by autonomic nervous system

Heart Physiology: Setting the Basic Rhythm
•	Coordinated heartbeat is a function of
–	Presence of gap junctions
–	Intrinsic cardiac conduction system
•	Network of noncontractile (autorhythmic) cells
•	Initiate and distribute impulses  coordinated depolarization and contraction of heart

Pacemaker (Autorhythmic) Cells
•	Have unstable resting membrane potentials (pacemaker potentials or prepotentials) due to opening of slow Na+ channels
–	Continuously depolarize
•	At threshold, Ca2+ channels open 
•	Explosive Ca2+ influx produces the rising phase of the action potential
•	Repolarization results from inactivation of Ca2+ channels and opening of voltage-gated 
K+ channels

Action Potential Initiation by Pacemaker Cells
•	Three parts of action potential:
–	Pacemaker potential
•	Repolarization closes K+ channels and opens slow Na+ channels  ion imbalance  
–	Depolarization
•	Ca2+ channels open  huge influx  rising phase of action potential
–	Repolarization
•	K+ channels open  efflux of K+

Sequence of Excitation
•	Cardiac pacemaker cells pass impulses, in order, across heart in ~220 ms
–	Sinoatrial node 
–	Atrioventricular node 
–	Atrioventricular bundle 
–	Right and left bundle branches 
–	Subendocardial conducting network (Purkinje fibers)

Heart Physiology: Sequence of Excitation
•	Sinoatrial (SA) node
–	Pacemaker of heart in right atrial wall
•	Depolarizes faster than rest of myocardium
–	Generates impulses about 75X/minute (sinus rhythm)
•	Inherent rate of 100X/minute tempered by extrinsic factors
•	Impulse spreads across atria, and to AV node

Heart Physiology: Sequence of Excitation
•	Atrioventricular (AV) node
–	In inferior interatrial septum
–	Delays impulses approximately 0.1 second
•	Because fibers are smaller diameter, have fewer gap junctions
•	Allows atrial contraction prior to ventricular contraction
–	Inherent rate of 50X/minute in absence of SA node input

Heart Physiology: Sequence of Excitation
•	Atrioventricular (AV) bundle
(bundle of His)
–	In superior interventricular septum
–	Only electrical connection between atria and ventricles
•	Atria and ventricles not connected via gap junctions

Heart Physiology: Sequence of Excitation
•	Right and left bundle branches
–	Two pathways in interventricular septum
–	Carry impulses toward apex of heart

Heart Physiology: Sequence of Excitation
•	Subendocardial conducting network
–	Complete pathway through interventricular septum into apex and ventricular walls
–	More elaborate on left side of heart
–	AV bundle and subendocardial conducting network depolarize 30X/minute in absence of AV node input
•	Ventricular contraction immediately follows from apex toward atria

Homeostatic Imbalances
•	Defects in intrinsic conduction system may cause
–	Arrhythmias - irregular heart rhythms
–	Uncoordinated atrial and ventricular contractions
–	Fibrillation - rapid, irregular contractions; useless for pumping blood  circulation ceases  brain death
•	Defibrillation to treat

Homeostatic Imbalances
•	Defective SA node may cause
–	Ectopic focus - abnormal pacemaker
–	AV node may take over; sets junctional rhythm (40–60 beats/min)
•	Extrasystole (premature contraction)
–	Ectopic focus sets high rate
–	Can be from excessive caffeine or nicotine

Homeostatic Imbalance
•	To reach ventricles, impulse must pass through AV node
•	Defective AV node may cause
–	Heart block
•	Few (partial) or no (total) impulses reach ventricles
–	Ventricles beat at intrinsic rate – too slow for life
–	Artificial pacemaker to treat

Extrinsic Innervation of the Heart
•	Heartbeat modified by ANS via cardiac centers in medulla oblongata
–	Sympathetic   rate and force
–	Parasympathetic   rate 
–	Cardioacceleratory center – sympathetic – affects SA, AV nodes, heart muscle, coronary arteries
–	Cardioinhibitory center – parasympathetic – inhibits SA and AV nodes via vagus nerves

Electrocardiography
•	Electrocardiogram (ECG or EKG)
–	Composite of all action potentials generated by nodal and contractile cells at given time
•	Three waves:
–	P wave – depolarization SA node  atria
–	QRS complex - ventricular depolarization and atrial repolarization
–	T wave - ventricular repolarization

Electrocardiography
•	P-R interval
–	Beginning of atrial excitation to beginning of ventricular excitation
•	S-T segment
–	Entire ventricular myocardium depolarized
•	Q-T interval
–	Beginning of ventricular depolarization through ventricular repolarization

Heart Sounds
•	Two sounds (lub-dup) associated with closing of heart valves
–	First as AV valves close; beginning of systole
–	Second as SL valves close; beginning of ventricular diastole
–	Pause indicates heart relaxation
•	Heart murmurs - abnormal heart sounds; usually indicate incompetent or stenotic valves

Mechanical Events: The Cardiac Cycle
•	Cardiac cycle
–	Blood flow through heart during one complete heartbeat: atrial systole and diastole followed by ventricular systole and diastole
–	Systole—contraction 
–	Diastole—relaxation
–	Series of pressure and blood volume changes 

Phases of the Cardiac Cycle
•	1. Ventricular filling—takes place in mid-to-late diastole
–	AV valves are open; pressure low 
–	80% of blood passively flows into ventricles
–	Atrial systole occurs, delivering remaining 20%
–	End diastolic volume (EDV): volume of blood in each ventricle at end of ventricular diastole

Phases of the Cardiac Cycle
•	2. Ventricular systole
–	Atria relax; ventricles begin to contract 
–	Rising ventricular pressure  closing of AV valves
–	Isovolumetric contraction phase (all valves are closed)
–	In ejection phase, ventricular pressure exceeds pressure in large arteries, forcing SL valves open
–	End systolic volume (ESV): volume of blood remaining in each ventricle after systole

Phases of the Cardiac Cycle
•	3. Isovolumetric relaxation - early diastole
–	Ventricles relax; atria relaxed and filling
–	Backflow of blood in aorta and pulmonary trunk closes SL valves
•	Causes dicrotic notch (brief rise in aortic pressure as blood rebounds off closed valve)
•	Ventricles totally closed chambers
–	When atrial pressure exceeds that in ventricles  AV valves open; cycle begins again at step 1

Cardiac Output (CO)
•	Volume of blood pumped by each ventricle in one minute
•	CO = heart rate (HR) × stroke volume (SV)
–	HR = number of beats per minute
–	SV = volume of blood pumped out by one ventricle with each beat
•	Normal – 5.25 L/min

Cardiac Output (CO)
•	At rest
–	CO (ml/min) = HR (75 beats/min)  SV (70 ml/beat) 
          	       = 5.25 L/min
–	CO increases if either/both SV or HR increased
–	Maximal CO is 4–5 times resting CO in nonathletic people
–	Maximal CO may reach 35 L/min in trained athletes
–	Cardiac reserve - difference between resting and maximal CO

Regulation of Stroke Volume
•	SV = EDV – ESV
–	EDV affected by length of ventricular diastole and venous pressure
–	ESV affected by arterial BP and force of ventricular contraction
•	Three main factors affect SV:
–	Preload
–	Contractility
–	Afterload

Regulation of Stroke Volume
•	Preload: degree of stretch of cardiac muscle cells before they contract (Frank-Starling law of heart)
–	Cardiac muscle exhibits a length-tension relationship
–	At rest, cardiac muscle cells shorter than optimal length
–	Most important factor stretching cardiac muscle is venous return – amount of blood returning to heart
•	Slow heartbeat and exercise increase venous return 
•	Increased venous return distends (stretches) ventricles and increases contraction force

Regulation of Stroke Volume
•	Contractility—contractile strength at given muscle length, independent of muscle stretch and EDV
•	Increased by
–	Sympathetic stimulation  increased Ca2+ influx  more cross bridges
–	Positive inotropic agents 
•	Thyroxine, glucagon, epinephrine, digitalis, high extracellular Ca2+
•	Decreased by negative inotropic agents
–	Acidosis, increased extracellular K+, calcium channel blockers

Regulation of Stroke Volume
•	Afterload - pressure ventricles must overcome to eject blood
•	Hypertension increases afterload, resulting in increased ESV and reduced SV

Regulation of Heart Rate
•	Positive chronotropic factors increase heart rate
•	Negative chronotropic factors decrease heart rate

Autonomic Nervous System Regulation
•	Sympathetic nervous system activated by emotional or physical stressors
–	Norepinephrine causes pacemaker to fire more rapidly (and increases contractility)
•	Binds to β1-adrenergic receptors   HR 
•	 contractility; faster relaxation
–	Offsets lower EDV due to decreased fill time

Autonomic Nervous System Regulation
•	Parasympathetic nervous system opposes sympathetic effects 
–	Acetylcholine hyperpolarizes pacemaker cells by opening K+ channels  slower HR
–	Little to no effect on contractility
•	Heart at rest exhibits vagal tone
–	Parasympathetic dominant influence 

Autonomic Nervous System Regulation
•	Atrial (Bainbridge) reflex - sympathetic reflex initiated by increased venous return, hence increased atrial filling
–	Stretch of atrial walls stimulates SA node    HR
–	Also stimulates atrial stretch receptors, activating sympathetic reflexes

Chemical Regulation of Heart Rate 
•	Hormones
–	Epinephrine from adrenal medulla increases heart rate and contractility
–	Thyroxine increases heart rate; enhances effects of norepinephrine and epinephrine
•	Intra- and extracellular ion concentrations (e.g., Ca2+ and K+) must be maintained for normal heart function

Homeostatic Imbalance
•	Hypocalcemia  depresses heart
•	Hypercalcemia  increased HR and contractility
•	Hyperkalemia  alters electrical activity  heart block and cardiac arrest
•	Hypokalemia  feeble heartbeat; arrhythmias

Other Factors that Influence Heart Rate
•	Age
–	Fetus has fastest HR
•	Gender
–	Females faster than males
•	Exercise	
–	Increases HR
•	Body temperature
–	Increases with increased temperature

Homeostatic Imbalances
•	Tachycardia - abnormally fast heart rate (>100 beats/min)
–	If persistent, may lead to fibrillation
•	Bradycardia - heart rate slower than 60 beats/min
–	May result in grossly inadequate blood circulation in nonathletes
–	May be desirable result of endurance training

Homeostatic Imbalance
•	 Congestive heart failure (CHF)
–	Progressive condition; CO is so low that blood circulation inadequate to meet tissue needs
–	Reflects weakened myocardium caused by
•	Coronary atherosclerosis—clogged arteries
•	Persistent high blood pressure
•	Multiple myocardial infarcts
•	Dilated cardiomyopathy (DCM) 

Homeostatic Imbalance
•	Pulmonary congestion
–	Left side fails  blood backs up in lungs
•	Peripheral congestion
–	Right side fails  blood pools in body organs  edema
•	Failure of either side ultimately weakens other
•	Treat by removing fluid, reducing afterload, increasing contractility

Developmental Aspects of the Heart
•	Embryonic heart chambers
–	Sinus venosus
–	Atrium
–	Ventricle
–	Bulbus cordis

Developmental Aspects of the Heart
•	Fetal heart structures that bypass pulmonary circulation
–	Foramen ovale connects two atria
•	Remnant is fossa ovalis in adult 
–	Ductus arteriosus connects pulmonary trunk to aorta
•	Remnant - ligamentum arteriosum in adult
–	Close at or shortly after birth

Developmental Aspects of the Heart
•	Congenital heart defects
–	Most common birth defects; treated with surgery
–	Most are one of two types:
•	Mixing of oxygen-poor and oxygen-rich blood, e.g., septal defects, patent ductus arteriosus
•	Narrowed valves or vessels  increased workload on heart, e.g., coarctation of aorta
–	Tetralogy of Fallot
•	Both types of disorders present

Age-Related Changes Affecting the Heart
•	Sclerosis and thickening of valve flaps
•	Decline in cardiac reserve
•	Fibrosis of cardiac muscle
•	Atherosclerosis