ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Conducting System of the Heart
Superior Atrioventricular node The sinoatrial node initiates the impulse for cardiac contraction.
vena cava (AV node) The atrioventricular node receives the impulse from the
Sinoatrial node sinoatrial node and transmits that impulse to the ventricles
(SA node) Left atrium through the bundle of His. The bundle divides into the right and
Pulmonary veins left bundle branches and Purkinje fibers to the two ventricles.
Right atrium
His bundle Sympathetic innervation from the T1 to T5 spinal cord segments
Right ventricle Left ventricle increases the heart rate, while the parasympathetics by way of
Inferior the vagus nerves slow the heart rate.
vena cava Bundle
branches
Purkinje
fibers
►►Associations of Common Traumatic Injuries with Vessel and Nerve Damage
Subclavian Brachiocephalic External iliac artery
artery trunk Inguinal ligament
Femoral artery
Clavicle Lateral
Axillary artery circumflex artery
Surgical neck Anterior humeral 1 Aortic arch Deep femoral artery Medial circumflex artery
fracture of circumflex artery (Supplies anterior (Major source of blood
humerus Medial epicondyle Superior thoracic and posterior thigh supply to head of femur)
Lacerates fracture artery and shaft of femur)
posterior humeral Superior ulnar collateral artery Popliteal artery
circumflex artery (may lesion ulnar n.) Thoracoacromial Popliteal artery
(may lesion axillary n.) Inferior ulnar collateral artery artery Anterior tibial artery
Common interosseus artery Anterior tibial artery Posterior tibial artery (Compressed
Teres major Pectoralis minor (Compressed with with tibial nerve in posterior
deep fibular nerve compartment syndrome)
Midshaft Lacerates Lateral thoracic in anterior compartment Peroneal artery
fracture of profunda brachii artery syndrome)
humerus artery (may lesion Medial plantar artery
radial n.) Subscapular artery Lateral plantar artery
(anastomoses with Plantar arch artery
Supra-condylar Lacerates suprascapular artery
fracture of to provide collateral
humerus brachial artery circulation around
(may lesion median n.) the axillary artery)
Radial collateral
artery
Radial artery
Ulnar artery
Deep palmar arch
Superficial palmar arch Dorsalis pedis artery
Anterior Posterior
Figure III-5-3. Arterial Supply to the Lower Limb
236
Cardiovascular Physiology ORGAN SYSTEMS │ 2. The Cardiovascular System
►► Comparison of ►►Cardiac Action Potentials—Ionic Mechanisms
Cardiac Action
PotentialsComparison of cardiac action potentials Unique Cardiac Ion Channels
+20 1 2 Ventricle iK Delayed rectifier; slow to open/close; depolarization opens
3 iK1
Em (mV) 0 L-type Inward rectifier; open at rest; depolarization closes it
0 if
Ca2+, slow channel, long acting; depolarization opens
4 4
-100 Na+; “funny channel”; repolarization opens it; causes the pacemaker
spontaneous depolarization
0
SA node Ionic Basis of Ventricular AP Ionic Basis of SA Node AP
Em (mV) 0 1 2 Slow Response (SA node) Cell Action Potential
3 0 and its Ionic Basis
44 200 msec
-80
0
+20 1 Atrium Em 0 3 Em 0 3
0 2 (mV) 4 (mV) 4 iK
Em (mV)
03 -65
4 4 -90 4 CURRENTS
-100 INWARD OUTWARD
Conductances gNa+ gK+ if
iCa
gCa++
►► Important Conductances show changes only, and do not reflect
Implications absolute values or relative values of different ions.
of Ion Currents
Conductances show changes only and do
Force development not reflect absolute values of different ions.
Ca2+ current of plateau (phase 2) has
major influence Ventricles and Atria SA Node and AV Node
Timing/heart rate Phase 4resting potential Phase 4pacemaker
if is increased by sympathetics → ↑ gK+ occurs via iK1 channels ↑HiggNh ag+Kv+iabuift “funny channel”
increased heart rate; parasympathetics iK channels are closing or closed ↓ as iK channels close
increase gK+ → decreased heart rate
Phase 0upstroke Phase 0upstroke
Premature beats ↑ gNa+ via typical fast Na+ channels ↑ gCa2+ via T-type (fast, transient) chan-
Action potential amplitude and shape not ↓ gK+ as iK1 channels close nels, then L-type (slow) open
all-or-none; early beats abnormal with
low force Phase 1rapid partial repolarization No phase 1 because no fast sodium chan-
↓ gNa+ as fast channels close nels
Susceptible period ↑ gK+ transiently via iKto
Arrhythmia risk high during relative Phase 2 usually absent
refractory period Phase 2plateau
↑ gCa2+: slow (L-type) channels
at end of phase 2, ↑ gK+ via iK channels
Phase 3repolarization Phase 3repolarization
↓ gCa2+ as L-type channels close ↓ gCa2+ as slow channels close
↑ gK+ via iK; then iK1 opens ↑ gK+ via iK channels
237
ORGAN SYSTEMS │ 2. The Cardiovascular System►►Refractory Periods
millivolts
Relative refractory period
Em (mV)
Summation is difficult to achieve in cardiac muscle and tetany does not occur. In fact, the abnormal shape of action potentials initiated
during the relative refractory period reduces calcium influx and thus contractile force, as shown.
Muscle Twitch Versus Refractory Periods Effect of AP Initiation During the Relative
Refractory Period
+30 +40 100 msec
Effective
refractory Muscle Twitch Force 0
period
0 1 4
23
-100 4
Active 3
Force
2
0 100 1
-100 200 300 400
Time Time (msec)
►►Basic Principles of the Electrocardiogram
A moving wave of depolarization in the heart produces a positive deflection as it moves toward the positive terminals of the ECG
electrodes. A depolarizing wave moving away from the positive (toward the negative) terminals produces a negative deflection. A wave
of depolarization moving at right angles to the axis of the electrode terminals produces no deflection. Upon repolarization, the reverse
occurs.
►►Sequence of Myocardial Excitation and Conduction
Event/Tissue Electrocardiogram
R R Sinoatrial node (SA) depolarizes Beginning of P wave
PR (primary pacemaker) P wave
Interval ST PT Between P wave and QRS complex
QS Conduction of depolarization through (PR interval)
segment QT interval atrial muscle QRS complex begins
QRS complex
PT Conduction through atrioventricular
node (AV) ST segment
QS T wave
Conduction through His-Purkinje
QRS system and ventricular septum
duration
Ventricular depolarization apex to
base; septum to lateral wall;
endocardial to epicardial
Ventricles are in the plateau phase
of depolarization
Repolarization of ventricles in
reverse sequence
238
Important ECG Values ORGAN SYSTEMS │ 2. The Cardiovascular System
PR interval 0.12–0.20 sec Length measures AV conduction time
QRS duration
QT interval <0.12 sec Measures ventricular conduction time
Heart rate, normal resting 0.35–0.45 sec Total time of ventricular depolarization and repolarization
Varies with heart rate, age
60–100 beats/min <60/min = bradycardia; >100/min = tachycardia
►►Principles of the Electrocardiogram (EKG or ECG)
Moving Electrical Charge Creates Electrical Field Movement That Causes Ion Currents in Skin
Standard limb leads I – right arm; ⊕ left arm; positive lead at 0°
(frontal plane) II – right arm; ⊕ left leg; positive lead at +60°
III – left arm; ⊕ left leg; positive lead at +120°
Augmented limb leads aVR; aVL, aVF aVR positive lead at –150°; aVL positive lead at −30°;
(frontal plane) aVF positive lead at +90°
Precordial V1−V6 (chest) Horizontal plane; positive leads front; negative leads back of chest
Chart speed 25 mm/sec Each horizontal mm = 0.04 sec (40 msec)
Voltage 1 mV/10 mm Measure ± voltages of QRS, add to get net voltage of each lead
Mean electrical axis Vector sum of two Measure of overall wave of ventricular depolarization: normal axis, left or right axis
leads deviation
Begin 1 sec 2 sec 3 sec
300
150
100
75
60
50
Lead I
Four intervals = 75 beats/min
OR
Four beats in 3 sec = 4 X 20 = 80 beats/min
Estimation of Heart Rate
Triplet Method Interval
How many dark lines are between R waves (5 mm apart)? Measure time interval (longer interval is better)
1 = 300/min; 2 = 150; 3 = 100; 4 = 75; 5 = 60; 6 = 50 Count R waves
Multiply count to convert to 1 minute
e.g., four R waves in 3 sec = 4 × 20 = 80 beats/min
239
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Important Rhythms to Recognize
Rhythm Characteristics
Sinus rhythm Each beat originates in the SA node; therefore, the P wave precedes each
Normal rate = 60−100 QRS complex; PR interval is normal
Bradycardia rate <60
Tachycardia rate >100
AV conduction block Abnormal conduction through AV node
First degree PR interval (> 0.20 sec); 1:1 correspondence; P wave:R wave
Second degree Mobitz I Progressively increased PR interval; then dropped (missing) QRS and then
(Wenckebach) repeat of sequence
Second degree Mobitz II Regular but prolonged PR interval; unexpected dropped QRS; may be a regular
pattern, such as 2:1 = 2 P waves:1 QRS complex or 3:1, etc.
Third degree (complete) No correlation of P waves and QRS complexes; usually high atrial rate
and lower ventricular rate
Premature ventricular contraction (PVC) Large, wide QRS complex originates in ectopic focus of irritability in
ventricle; may indicate hypoxia
Ventricular tachycardia Repeated large, wide QRS complexes like PVCs;
Rate 150−250/min; acts like prolonged sequence of PVCs
Ventricular fibrillation Total loss of rhythmic contraction; totally erratic shape
►►Evolution of an Infarction: Signs on the EKG
Features to observe QRS complex Presence of prominent Q waves in leads where
normally absent: infarct damage
ST segment Elevation or depression: acute injury
T wave Inversion; e.g., downward in lead where usually
positive: acute ischemia
Acute myocardial infarction (MI) Minutes to a few days ST segment elevation or depression
Inverted T waves
Prominent Q waves
Resolving infarction (healing) Weeks to months Inverted T waves
Prominent Q waves
Stable (old) MI Months to years Prominent Q waves as result of MI persist for the
rest of life
Caution: Not all infarctions produce Q waves. Inverted T waves and/or ST abnormalities should always be investigated, even
in absence of significant Q waves.
►►Identifying Location of an Infarction
Location Principal Feature of ECG Vessel Involvement
Posterior Large R with ST depression in V1 and V2: Right coronary artery
Mirror test or reversed transillumination
Lateral Q waves in lateral leads I and AVL Circumflex coronary artery
Inferior Q waves in inferior leads II, III & AVF Right or left coronary artery
Anterior Q waves in V1, V2, V3 & V4 Anterior descending coronary artery
240
►►Mean Electrical Axis (MEA) ORGAN SYSTEMS │ 2. The Cardiovascular System
Definition • Overall direction and force (vector) of the events of ventricular depolarization: obtained
by vector sum of net voltage of two leads or by quadrant method using leads I and aVF
• MEA tends to shift toward large mass and away from an MI
Normal axis • Expected in the absence of cardiac disease
• R wave: lead I, +; lead II, +; lead III, +
Left axis deviation • May indicate left heart enlargement, as in hypertrophy or left dilated failure
• Abnormally prolonged (slow) left ventricular conduction
• Right heart MI, expiration, obesity, lying down
• R wave: lead I, +; lead II, +; lead III, –
Right axis deviation • Right ventricular hypertrophy or dilation
• Prolonged right conduction
• Left heart MI, inspiration, tall lanky people, standing up
• R wave: lead I, –; lead II, +; lead III, +
Extreme right axis deviation Difficult interpretation; one example: depolarization proceeding from abnormal focus in
LV apex
Einthoven’s Triangle: Leads I, II, and III* Vector Cardiogram
–90° lead aVF - lead aVF -
–120 +90° –60 Voltages:
aVF lead l + lead l +
+180 lead l - extreme left axis lead l + lead l -
right axis deviation lead aVF+
+120 deviation normal axis
III
– I+ right axis normal lead aVF +
–– deviation lead aVF -
II III
0I lead l +
++
lead aVF +
lead aVF -
+60 lead l + lead l -
II lead l -
Essentials of the EKG lead aVF + lead aVF +
Heart rate
Rhythm Voltages: Voltages
lead l+ lead l -
Axis deviation lead aVF- lead aVF+
Hypertrophy left axis deviation right axis deviation
Infarction
*The figure adds aVF because the quadrant method of determining axis uses leads I and aVF.
241
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Cardiac Mechanical Performance
Factor Definition Effects
↑ preload causes ↑ active force development up
Preload Cardiac muscle cell length (sarcomere length) before
contraction begins to a limit
↑ afterload ↓ the volume of blood ejected during
Afterload Load on the heart during ejection of blood from the ventricle
a beat
Contractility Capacity of the heart to produce active force at a specified High contractility ↑ ability to work
Rate preload Low contractility ↓ ability to work
↑ output of blood per minute, but ↓ output per
Heart rate (HR): number of cardiac cycles per minute
beat; very high rate (>≈150/min) ↓ output
►►Cardiac Performance: Definitions
Stroke volume (SV) Blood ejected from ventricle per beat = EDV – ESV
End diastolic volume (EDV) Volume of blood in ventricle at end of diastole; the preload
End systolic volume (ESV) Volume of blood remaining in ventricle at end of systole
Cardiac output (CO) Volume of blood per minute pumped by the heart; CO = SV × HR
Ejection fraction (EF) Measure of contractility: EF = SV/EDV
Left ventricular dP/dT (mm Hg/sec) Measure of contractility: maximum rate of change of pressure during
isovolumic contraction
►►Cardiac and Vascular Function Curves
Cardiac function curve • CFC generated by controlling preload and measuring cardiac output, stroke volume or other measure of
(CFC) systolic performance
• ↑ preload improves actin-myosin interdigitation and thus ↑ SV, CO, etc.
• CFC shifts up with ↑ contractility; down with ↓ contractility; so a new curve is produced when
contractility changes
• Moving to a different point on the same CFC is a change only of preload: moving to a different CFC is
change of contractility
Vascular function • VFC relates venous return to right atrial pressure
curve (VFC) • ↑ blood volume shifts VFC up, ↓ volume shifts VFC down
Equilibrium point Cardiac output is determined by both CFC and VFC. Intersection of the CFC and VFC is the stable operating
point; if contractility or blood volume changes, the system will operate at the intersection
of the two new curves.
►►Cardiovascular Responses in Exercise
Heart Rate TPR MAP Cardiac Output
Aerobic, Increased Decreased Minimal change Increased
Dynamic
Anaerobic, Increased Increased Increased Increased, unchanged,
Static or decreased*
*Cardiac output during static or anaerobic exercise is highly dependent on the type and
intensity of exercise.
Definition of abbreviations: MAP, mean arterial pressure; TPR, total peripheral resistance.
242
►►Cardiac and Vascular Function Curves: Examples ORGAN SYSTEMS │ 2. The Cardiovascular System
Stability of Typical CFC and VFC Changes in Blood Volume
10 10
8 Increased blood volume
Cardiac Output (L/min) Cardiac Function Cardiac Output (L/min)
Curve
8 CB
6D 6
A Initial Point
4 4 Normal Volume
2
Equilibrium Vascular Function Curve
2 Point
Hemorrhage
0 0 10
-2 0 2 4 6 8 -2 0 2 4 6 8
Central Venous Pressure (mmHg) 10 Central Venous Pressure (mmHg)
Diagram shows that cardiac output (CO, 5 L/min) changes only Increased blood volume (e.g., transfusion) shifts the VFC
transiently when CFC and VFC are not changed. Point A: venous upward, which increases preload. Increased CO follows.
pressure is increased from 3 to 6 mm Hg because of sudden removal Decreased blood volume (e.g., hemorrhage) shifts the VFC
of blood from arterial system and injection into venous system. This downward, which decreases preload. Decreased CO follows.
causes CO to increase to point B. CO then returns to equilibrium Increases and decreases in preload produce increases and
point in steps (B → C, C → D) as blood is pumped from venous decreases in CO by the Frank-Starling mechanism.
system back to arterial system.
Sympathetic Stimulation of Heart Changes in CO After Heart Failure
10 Progressive Changes of Heart Failure
Cardiac Output (L/min) 8B Cardiac Output (L/min) 10 NMoormdearlaVtoeluHmySepeevrevroeleVmoilaume Extreme Volume Normal
C 8
6 Compensated Failure
6D
A AC
4 4 Decompensated
2 B DE
Initial Point 2
0 0 10
-2 0 2 4 6 8 -2 0 2 4 6 8
Central Venous Pressure (mmHg) 10 Central Venous Pressure (mmHg)
Increased contractility by cardiac sympathetic nerve stimulation shifts Reduced contractility shifts CO down (point B), but preload
the CFC upward (dashed line); however, this does not change the immediately increases to intersect with the normal volume
VFC. The initial large increase in CO (point B) returns to point D on curve as shown. Within hours to days, blood volume increases,
the VFC as blood is transferred from the venous system to the arterial shifting VFC upward, and point C becomes the equilibrium
system. point. With progressive failure, blood volume cannot increase
enough to maintain CO at a normal level. (point D). Blood
volume continues to increase, which overstretches the heart
(point E).
243
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►The Cardiac Cycle: the Wigger’s Diagram
Pressure (mmHg) Ejection Isovol. relax.
Atrial Systole Rapid ventricular
Isovol. contract. filling
Slow ventricular
filling
Diastasis
120 Aortic aortic valve aortic valve
mitral valve opens closes
0 closes
5 mitral valve
Ventricular opens
left atrial pressure
Aortic Blood aortic flow is measured at the root, or origin
Flow (L/min)
0
Ventricular 40
Volume (ml)
20 1 23
4
Venous Pulse
Electrocardiogram (mmHg) Heart a c v
6
Sounds
0 R
P
T P
QS
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
Time (sec)
Left ventricular pressure Systole: begins at isovolumic contraction, ends at Diastole: begins at beginning of isovolumic
beginning of isovolumic relaxation: two phases are relaxation and ends at onset of isovolumic
isovolumic contraction and ventricular ejection contraction: two phases are isovolumic relaxation
and ventricular filling
Aortic pressure Maximum is systolic pressure. During ejection, Minimum is diastolic pressure. Pressure falls during
aortic pressure is slightly below ventricular diastole as blood flows from aorta into capillaries
pressure. and then veins.
Left atrial pressure Systole; isolated from ventricular pressure Diastole, blood flows from atrium into ventricle
because mitral valve is closed because mitral valve is open. Note mitral closed
during isovolumic relaxation.
Aortic flow (measured Systolic ejection begins when ventricular pressure Ejection ends when rapidly falling ventricular
at root)
exceeds aortic diastolic and aortic valve opens. pressure causes aortic valve to close.
Ventricular volume Maximum at end of diastole; does not change Minimum at end of ejection phase; does not change
during isovolumic contraction because mitral and during isovolumic relaxation (both valves closed).
aortic valves are closed.
Heart sounds Systole: S1 caused by sound of mitral closure S2 caused by sound of aortic valve closure
Venous pulse Rises with atrial systole Drops as atrium fills
EKG QRS begins before isovolumic contraction T wave begins during late ejection phase
244
►►Cardiac Pressure–Volume Loops (PV Loops) ORGAN SYSTEMS │ 2. The Cardiovascular System
Phase Pressure Volume
Filling Slightly ↑ Large ↑; point C = EDV
Isovolumic contraction Rapid ↑; maximum dp/dt No change, valves closed
Ejection Continues to rise ↓ as ejection proceeds
No change, valves closed
Isovolumic relaxation Rapid ↓
Area within loop = stroke work output Applications
Increase work by ↑ stroke volume (volume work) or by ↑ LVP
Decreased blood volume (pressure work)
(hemorrhage, dehydration, urination) Line C−D shift left (↓ preload); ↓ stroke volume ↓ stroke work
Increase in contractility
(sympathetics, or β-adrenergic drugs, digitalis) Line F−A shifts left (↓ ESV) a major effect; slight ↓ EDV; overall ↑
Decreased contractility, as in heart failure stroke volume, ↑ stroke work
Loop shifts to right and systolic pressure is lower: ↑↑ ESV, ↑ EDP,
Volume expansion (normal heart) ↓ SV, ↓ stroke work
Line C−D shifts right (↑ EDV); ↑ SV; ↑ stroke work
Normal PV Curve Blood Volume Changes
150 E 150
F
100
Stroke Volume
50
Hemorrhage
0
0 50 100 150
Left Ventricular Volume (ml)
Left Ventricular Pressure (mm Hg) aortic valve
Left Ventricular Pressure (mm Hg)opens
Increased Blood Volume
100
aortic valve closes
Stroke Volume D
50
mitral valve opens
mitral valve closes
A B C
0 50 100 150
Left Ventricular Volume (ml)
0
A–B: rapid filling D–F: ejection phase • D ecreased blood volume (hemorrhage, dehydration):
B–C: reduced or slower filling F: end systolic volume (ESV) Line C–D shifts left (↓ preload); ↓ stroke volume, ↓ stroke work
C: end diastolic volume (EDV) F–A: isovolumic relaxation • Volume expansion (normal heart):
C–D: isovolumic contraction Line C–D shifts right (↑ EDV), ↑ SV, ↑ stroke work
• Diastolic dysfunction tends to ↓ EDV despite ↑ EDP
• Area within loop = stroke work • S ystolic dysfunction tends to ↑ ESV and ↓ systolic LVP
• I ncrease work by ↑ stroke volume (volume work) or by
(Continued)
↑ LVP (pressure work)
245
ORGAN SYSTEMS │ 2. The Cardiovascular System
Left Ventricular Pressure
Left Ventricular Pressure
Left Ventricular Pressure
►►Cardiac Pressure–Volume Loops (PV Loops; Cont’d.)
Increased Afterload Decreased Afterload Progressive Heart Failure
Increased 150 150
Afterload Normal (A)
150 Decreased
Afterload
100 100 100 B
Stroke Volume Stroke Volume C
50
D
0 50 50
0 50 100 150
Left Ventricular Volume (ml) 0
0 0 50 100 150
With increased afterload (e.g., ↑ aortic 0 50 100 150 Left Ventricular Volume (ml)
pressure), the velocity of shortening Left Ventricular Volume (ml)
and the distance shortened are both A. Normal left ventricular function. B. Immediate effec
decreased. Thus, ESV increases, of reduced contractility, no compensation.
causing SV to decrease. C. Compensated LV failure: SV is partially restored
because of moderately increased preload.
Decreased afterload produces the opposite D. AD:eNcoomrmpeanlsated failure: despite extreme increases
changes as increased afterload. Thus, ESV of pBre: lAoacdu,tethleoSssV oref mcoanintsralocwti,litayndwinthfoauct the heart is
beingcovmeprley nsstraeticohned, so additional "compensation" is
decreases and SV increases. actuCa:llCy ohmarmpefunls. ated LV failure (SV partially
restored because of moderate increase in
preload)
D: Decompensated failure (SV remains low
despite ↑↑↑ in preload)
Overall: Curves shift to the right and systolic
pressures ↓.
Heart failure: ↑↑↑ ESV, ↑ EDV, ↓ SV,
↓ stroke work
►►The Cardiac Valves
Mitral Between LA and LV Open during filling Closed during ventricular systole and isovolumic relaxation
Open during ejection Closed during diastole and isovolumic contraction
Aortic Between LV and aorta Open during filling Closed during ventricular systole and isovolumic relaxation
Open during ejection Closed during diastole and isovolumic contraction
Tricuspid Between RA and RV
Pulmonic Between RV and
pulmonary artery
Isovolumic Both Valves Closed Isovolumic
Contraction Relaxation
Left Ventricular Volume
Aortic Valve Time
OPEN
Mitral Valve
OPEN OPEN
Second Heart Sound
First Heart Sound aortic and pulmonic
mitral closure closure
246
►►Valvular Disorders Aortic Regurgitation ORGAN SYSTEMS │ 2. The Cardiovascular System
Aortic Stenosis 160
160
Pressure (mm Hg) 90 Aortic Pressure Pressure (mm Hg)
0 Atrial Pressure 40 Aortic Pressure
Ventricular Pressure
0 Atrial Pressure
SM Ventricular Pressure
• Discrepancy of systolic LV and systolic aortic pressures • D iastolic aortic P decreases rapidly as blood flows
• Causes crescendo-decrescendo systolic murmur back into ventricle; ventricular diastolic P is elevated.
Mitral Valve Stenosis • Causes diastolic murmur
Mitral Regurgitation
100
Aortic Pressure 120
Aortic Pressure
Pressure (mm Hg) Pressure (mm Hg)
80
20 Atrial Pressure
0 Ventricular Pressure Atrial Pressure
0 Ventricular Pressure
SM
• Discrepancy of diastolic LVP and left atrial P during filling • I ncompetent valve allows backflow into left atrium
• Causes diastolic murmur during ventricular systole
Definition of abbreviation: SM, systolic murmur. • Causes systolic murmur
247
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Hemodynamics • Flow (Q); P1 (input pressure); P2 (output pressure); R (resistance); (P1 − P2) = pressure gradient
• ↑ pressure gradient → ↑ flow
Poiseuille’s equation:
Q = (P1 – P2)/R • ↑ resistance → ↓ flow
Series circuits:
RT = R1 + R2 + R3 …..Rn • RT = total resistance Series system Q equal at all points Po
• Flow is equal at all points in series circuit; Pressure drops across each resistor
Parallel circuits: Pi P1 P2
I/RT = 1/R1 + 1/R2 +1/R3... pressure drops across each resistor
..1/Rn R1 R2 R3
• A dding more resistors in series
Hydraulic Resistance increases RT. Pressure drop increases Q Q Q QQ
Equation: along circuit with constant flow, and flow
decreases with constant input pressure Pi = input pressure Po = output pressure
R = (P1 – P2)/Q = 8ηl/πr4 (P1).
Pi - Po = (Pi -P1) + (P1-P2) + (P2 - Po)
Total peripheral resistance • Various types of blood vessels lie in series.
(TPR) RT = (Pi - Po) /Q
Total peripheral resistance • Flow divided between parallel resistors
equation Pi Q- PRo1 = (Pi - P1) + (P1 - P2) +(P2 - Po)
• R T is always lower than the lowest resistor QQ Q
TPR = (MAP – RAP)/CO • Adding more resistors in parallel
RT = R1Q+1 R2 + R3
Compliance (C): decreases RT. R2
C = ∆V / ∆P • Produces low resistance circuit QT P1 Q2 P2 QT
Pulse pressure (PP): • Organs lie in parallel R3
PP = SP – DP
Q3
QT = Q1 + Q2 + Q3
1 = 1 + 1+ 1
RT = R1 R2 R3
• η = viscosity; l = length; r = radius • 2× radius = 1/16 R → 16 × flow
• ½ radius = 16 × R → 1/16 × flow
• Viscosity ↑ by ↑ hematocrit • Control of radius is the dominant mechanism
• Viscosity ↓ in anemia to control resistance.
• l is usually constant; r changes greatly for
normal regulation and in disease.
• Resistance of peripheral circuit: aorta → right atrium
• TPR ↑ by sympathetics, angiotensin II, and other vasoconstrictors
• Highest TPRs in arterioles; also main site of blood flow regulation
• Mean arterial pressure (MAP); right atrial pressure (RAP)
• Pressure gradient is between aorta and right atrium.
• TPR is calculated from MAP and cardiac output (CO). RAP is assumed to be 0 mm Hg, unless
specified.
• TPR is also known as SVR (systemic vascular resistance)
• ∆V = volume change; ∆P = pressure change Aorta
Arteries
• High compliance means vessels easily Arterioles
distended by blood. Capillaries
Venules
• Elasticity is inverse of compliance; vessels Veins
are stiff when elasticity is high Vena Cavae
Right Atrium
120
• S P = systolic pressure; DP = diastolic 80mmHg
pressure
40
↓ compliance (e.g., arteriosclerosis) → ↑ SP
and ↓ DP, so PP ↑ 0
• Compliance: systemic veins > pulmonary • MAP = diastolic + 1/3 (pulse pressure)
circuit > systemic arteries (volume of blood is • MAP = 80 + 1/3(120 – 80) = 80 = 13 =
in same order)
93 mm Hg
(Continued)
248
►►Hemodynamics (Cont’d.) ORGAN SYSTEMS │ 2. The Cardiovascular System
Cardiac output • CO = V• O2 /(Ca – Cv) • Used to measure cardiac output; most accurate
(Fick method) • V • O2 = oxygen consumption, Ca = arterial if Ca is pulmonary venous and Cv is pulmonary
arterial
oxygen content, Cv = venous oxygen content
►►Area-Velocity Relationship
• V∝ 1/cross sectional area 4000Cross sectional Area (cm2) 50
• V ∝1/r2, 2000 Aorta Mean
• V = velocity; r = radius Arteries Velocity
0 Arterioles
• A ssuming total flow is equal in all vessel types, velocity Capillaries 25 (cm/sec)
increases as radius decreases. Venules 0
Veins
• T he aorta is a single large vessel, but its total area is small Vena Cavae
compared with numerous capillaries in parallel. Right Atrium
• I f low capillary velocity allows adequate time for diffusion,
exchange is perfusion limited.
• I f velocity is high, metabolic exchange may become diffusion
limited.
= cross sectional area
= mean velocity
►►Pressures of the Cardiovascular System
Pulmonary Lungs Pulmonary • The cardiac output and stroke volume of the left
Artery RA LA Vein and right heart are nearly equal.
RV LV Aorta & Systemic • The mean pressures are different because the systemic
Peripheral Arteries resistance is about 6× higher.
Organs • The pulse pressure in the pulmonary circulation
is lower because its compliance is higher.
Systemic
Veins
Pressures in the Pulmonary Circulation (mm Hg) Pressures in the Systemic Circulation (mm Hg)
Right ventricle 25/0 Left ventricle 120/0
Pulmonary artery 25/8 Aorta 120/80
Mean pulmonary artery 14 MAP 93
Capillary 7–9 Capillary: skeletal <30
Renal glomerular 45–50
Pulmonary vein 5 Peripheral veins <15
Left atrium <5
Pressure gradient 15 – 5 = 10 Right atrium 0
Pressure gradient 93 – 0 = 93
249
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Factors That Control Filtration and Reabsorption in Capillaries
Factors that influence ultrafiltration and reabsorption in capillaries.
Favor Filtration Favor Reabsorption
Plasma Pcap πcap or
Kf
Interstitial Fluid πtissue Ptissue
Tissue
Filtration = Kf ( forces favor - forces opposed)
Filtration = Kf [ (Pcap + πtissue) - (Ptissue + πcapillary) ]
Filtration = Kf (forces favor − forces opposed)
Filtration = Kf [(Pcapillary + πtissue) − (Ptissue + πcapillary)]
Ultrafiltration coefficient (Kf) • Related to surface area, capillary porosity; different in each tissue/organ
Capillary hydrostatic pressure (Pcap) • Determines amount of ultrafiltration to given filtration pressure
Tissue (interstitial) oncotic pressure (πtissue)
Capillary (plasma) oncotic pressure (πcap) • Favors filtration; ↑ Pcap → ↑ filtration
• Controlled by input pressure, arteriolar diameter, venous pressure
Tissue (interstitial) hydrostatic pressure (Ptissue)
• Favors filtration; ↑ πtissue →↑ filtration
• Directly related to [protein] in interstitial fluid
• Example: ↑ permeability (e.g., sepsis) →↑ πtissue →↑ filtration
• Opposes filtration; ↑πcap →↓ filtration
• Directly related to [protein] in plasma
• Examples:
− Liver failure ↓πcap → edema
− Dehydration ↑πcap → reabsorption
• I ncreases filtration when negative (is normally negative in many but not all
tissues)
• Opposes filtration when positive; edema causes positive pressure in
interstitium, even when pressure is normally negative.
250
►►Factors That Alter Capillary Flow and Pressure ORGAN SYSTEMS │ 2. The Cardiovascular System
Resistance Capillary Capillary Example
Flow Pressure β-adrenergic agonist, α-adrenergic blocker,
decreased sympathetic nervous system activity,
Arteriole dilation ↓ ↑↑ metabolic dilation, ACE inhibitors
Arteriole constriction ↑ ↓↓ α-adrenergic agonist, β-adrenergic blocker,
increased sympathetic nervous system activity,
Venous dilation ↓ ↑↓ angiotensin II
Venous constriction ↑ ↓↑
Increased metabolism of tissue
Increased arterial pressure N ↑↑
Decreased arterial pressure N ↓↓ Physical compression, increased sympathetic
activity
Increased venous pressure N ↓↑
Decreased venous pressure N ↑↓ Increased cardiac output, volume expansion
Decreased cardiac output, hemorrhage,
dehydration
Congestive heart failure, physical compression
Hemorrhage, dehydration
►►Wall Tension: Law of Laplace
T=P×r • Tension (T) in wall Aortic Aneurysm
• ↑ pressure and ↑ radius → ↑ tension Increased radius
Applications Arterial aneurysm: Pressure
• Weak wall balloons
• Vessel radius ↑, causing ↑ wall tension. Increased Tension
• ↑ tension causes ↑ radius (vicious cycle), increasing risk of Risk of dissection and rupture!
rupture
Dilated heart failure:
• ↑ ventricular volume → ↑ ventricular radius, which in turn causes
↑ wall tension.
• Thus, dilated ventricle must work harder than normal heart
251
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Autonomic Control of Heart and Circulation Parasympathetic
Sympathetic Acetylcholine: muscarinic
↓ rate (↑ gK, ↓ if ): – chronotropic
Heart Norepinephrine: β1-adrenergic Modest effects: – inotropic
Transmitter-receptor ↑ rate (if and Ca2+ currents): ⊕ chronotropic ↓cAMP; ↓gCa2+ mainly at very high levels of
Heart rate
↑ force (dp/dt, EF): ⊕ inotropic activity only
Contractility ↑ gCa2+, ↑ cAMP, ↑ Ca2+ release from SR, ↓ ↓ atrial and ventricular conduction
duration: fast, strong, short duration ↓ conduction AV node
↑ PR interval of EKG
Conduction ↑ atrial and ventricular conduction No direct innervation of vascular smooth muscle
Arteries/arterioles ↑ conduction AV node
Veins ↓ PR interval of EKG No direct innervation
Norepinephrine: α1 (mainly) constriction
Epinephrine (adrenal): β2 dilation
High levels: α1 constriction
Norepinephrine: α1 (mainly) constriction but
not usually much ↑ resistance,
rather, ↓ capacitance shifts blood
toward heart
►►Control of Organ Blood Flow
Organ/Tissue Neural Metabolic/Other
• Metabolic vasodilation dominates in exercise
Skeletal muscle Resting: α-adrenergic constriction • Compression during static exercise blocks flow
Exercising: β-adrenergic dilation
Skin • Heat dilates, cold constricts, a direct effect
Heart (epinephrine, adrenal medulla)
• Metabolic dilation is dominant
• Thermoregulatory center • ↑ Cardiac work → ↑ O2 consumption →↑ coronary
• α-adrenergic constriction only
flow
• α-adrenergic constriction • Compression during systole, so most coronary flow
• β-adrenergic dilation
• Overridden by metabolism is during diastole
• Metabolism dominates: ↑ CO2 → dilation
Brain Not generally under neural control:
autoregulation
►►AutoregulationBlood Flow Regulation of blood flow within the organ itself
Autoregulatory Range Autoregulating Organs
Blood Pressure (mmHg) • Cerebrum
• Heart
• Exercising muscle
• Gastrointestinal tract
• Kidney (not metabolic autoregulation)
252
►►Basics of Integrated Control of Arterial Pressure and Cardiac Output ORGAN SYSTEMS │ 2. The Cardiovascular System
Control Major Actions
Baroreceptors: ↑ pressure →↑ activity ↑ activity → ↑ PNS and ↓ SNS
Carotid sinus (primary) ↓ pressure →↓ activity ↓ activity → ↓ PNS and ↑ SNS
Aortic arch (secondary)
Sympathetic (SNS) ↑ pressure → ↓ SNS • Vasoconstriction (↑ α-adrenergic) → ↑ TPR
Parasympathetic (PNS) ↓ pressure → ↑ SNS • ↑ Contractility heart (↑ β-adrenergic) → ↓ ESV → ↑ SV
Renal • ↑ Heart rate (β-adrenergic)
↑ pressure → ↑ PNS • ↑ Cardiac output (CO)
↓ pressure → ↓ PNS
• ↓ heart rate (major); ↓ contractility (minor)
↑ MAP → ↓ renin, angiotensin II (AII) • At rest, PNS dominant control of heart rate
↑ MAP →↑ urination →↓ volume →↓ • ↓ cardiac output
preload • AII vasoconstricts
• Renal control of blood volume and TPR dominant
long-term control of blood pressure and CO
►►Selected Applications of the Diagram
Heart Rate Contractility Preload Hemorrhageenter at blood volume (↓)
Stroke Volume Blood Volume Heart failureenter at contractility (↓)
Vasodilator drugenter at TPR (↓)
Cardiac Output Total Peripheral
Resistance
Mean Arterial Pressure Urine Volume Vasoconstrictor drugenter at TPR (↑)
Baroreceptor Activity renin Diureticsenter at urine volume (↑)
Carotid massageenter at baroreceptor (↑)
angiotensin II ACE inhibitorenter at angiotensin II* (↓)
Parasympathetic Nervous Sympathetic Nervous
System Activity System Activity
Stimulates
Inhibits
*Note: also would increase urine flow through reduction of aldosterone (not shown in figure)
253
ORGAN SYSTEMS │ 2. The Cardiovascular System Cardiovascular Pathology
►►Congenital Abnormalities of the Heart
• Congenital abnormalities occur before the end of week 16 (completion of heart development).
• Clinical significance depends on degree of shunt.
• Up to 90% of congenital heart disease is of unknown etiology.
• Maternal rubella: exposure at fifth to tenth week can lead to PDA, ASDs, and VSDs.
• Fetal alcohol syndrome: cardiovascular defects, including VSD
Acyanotic (Late Cyanosis) Congenital Heart Disease (Left-to-Right Shunts)
Initially a left-to-right shunt; causes chronic right heart failure and secondary pulmonary hypertension. Increased pressure causes
reversal of shunt flow with late onset cyanosis: Eisenmenger syndrome
Ventricular septal defect • Usually of membranous interventricular septum
(VSD) • Often associated with other defects, including trisomy 21
Atrial septal defect (ASD) Ostium primum defect (5% of ASDs):
• Defect in lower atrial septum above the atrioventricular valves
• Associated with anomaly of AV valves
• Requires antibiotic prophylaxis for invasive procedures
Ostium secundum defects (90% of ASDs):
• Defect is in center of the atrial septum at the foramen ovale
• Results from abnormalities of septum primum and/or septum secundum
• AV valves normal
• Antibiotic prophylaxis not needed
Complete endocardial Combination of ASD, VSD, and a common atrioventricular valve
cushion defect
Sinus venosus • Defect in the upper part of the atrial septum
• May cause anomalous pulmonary venous return into superior vena cava or right atrium
Patent foramen ovale • Remnant of the foramen ovale, usually not of clinical significance
• Risk of paradoxical emboli
Patent ductus arteriosus In the fetal circulation, the PDA shunts blood from the pulmonary artery into aorta. At birth, the pressure
(PDA) differential changes, and the flow is reversed (from aorta to pulmonary artery). This leads to pulmonary
hypertension due to excess blood flowing through pulmonary artery.
Pharmacology:
• Indomethacin: closes PDA
• Prostaglandin E: keeps PDA open
Cyanotic Congenital Heart Disease (Right-to-Left Shunts)
• Right-to-left shunt bypasses the lungs and hence produces cyanosis as early as birth.
• Paradoxical embolism (DVT causes systemic infarct) may occur.
Tetralogy of Fallot • Most common cyanotic congenital heart disease in older children and adults
• Associated with trisomy 21
• Four lesions:
1) VSD
2) An overriding aorta that receives blood from both ventricles
3) Right ventricular hypertrophy
4) Pulmonic stenosis (right ventricular outflow obstruction)
(Continued)
254
Cyanotic Congenital Heart Disease (Right-To-Left Shunts; Cont'd.) ORGAN SYSTEMS │ 2. The Cardiovascular System
Transposition of the • Failure of the truncoconal septum to spiral
great vessels
• The aorta arises from the right ventricle, and the pulmonary artery arises from the left ventricle,
producing two closed loops. This is fatal if a shunt (e.g., PDA, VSD, ASD, patent foramen ovale) is not
present to mix the venous and systemic blood.
Persistent truncus • Failure of the truncus arteriosus to separate into the aorta and pulmonary arteries
arteriosus • Usually a membranous VSD
• Truncus arteriosus receives blood from both ventricles, so cyanosis results.
Definition of abbreviation: DVT, deep venous thrombosis.
►►Obstructive Congenital Heart Disease
Does not usually cause cyanosis
Coarctation of the aorta Preductal (infantile) type:
• Narrowing of the aorta proximal to the opening of the ductus arteriosus
• May be associated with cyanosis of the lower half of the body
• Often requires surgery
Postductal (adult) type:
• Narrowing of the aorta distal to the opening of the ductus arteriosus
• Most common type; allows survival into adulthood
• Disparity in pressure between the upper and lower extremities
• Collateral circulation leads to rib notching
Pulmonic valve stenosis or • U nequal division of the truncus arteriosus so that the pulmonary trunk has no lumen or opening at
atresia the level of the pulmonary valve
• May cause cyanosis if severe
Aortic valve stenosis Complete atresia: incompatible with life
or atresia
Bicuspid aortic valves: asymptomatic, can lead to infective endocarditis, left ventricular overload, and
sudden death
• Calcify fifth to sixth decade (tricuspid aortic valves usually calcify 10 years later)
• Most common cause of aortic stenosis (more than rheumatic fever)
Diseases Associated with Congenital Heart Defects
Marfan syndrome: 1/3 patients have aortic dilatation and incompetence, aortic dissection, and ASD
Down syndrome: 20% of patients may have congenital cardiovascular disease
Turner syndrome: Coarctation of the aorta
22q11 syndromes (DiGeorge syndrome and velocardial facial syndrome): Truncus arteriosus and tetralogy of Fallot
Congenital rubella: Septal defects, patent ductus arteriosus, pulmonary artery stenosis
Maternal diabetes: Transposition of great vessels
255
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Ischemic Heart Disease
• Leading cause of death
• Most angina pectoris caused by severe atherosclerotic narrowing of coronary arteries
• Result of decreased supply (anemia, carbon monoxide, pulmonary disease) and/or increased demand (exertion, hypertrophy)
• Sudden cardiac death the presenting symptom in 25% of patients with IHD
Angina pectoris • Paroxysmal substernal or precordial chest pain
• Transient myocardial ischemia without myocardial infarction
Stable angina pectoris • Paroxysms are associated with a fixed amount of exertion, e.g., after walking three blocks
• Typical attacks last less than 10 minutes and are relieved with rest or sublingual nitroglycerin
• ECG may show ST segment depression (ischemia limited to subendocardium)
Prinzmetal angina • Vasospasm causes decreased blood flow through atherosclerotic vessels
• This form of attack frequently occurs at rest with ST-segment elevation on ECG
• Treat with calcium channel blockers
Unstable angina • C hest pain with progressively less exertion, then occurring at rest, often precedes myocardial infarction
• May be unresponsive to nitroglycerin
►►Myocardial Infarction
• Ischemic necrosis of myocardium, most commonly transmural, but can be subendocardial
• Highest incidence of fatal MI: 55 to 64 years old
• R isk factors: male sex, hypertension, hypercholesterolemia, cigarette smoking, family history, diabetes mellitus, oral contraceptive
use, sedentary lifestyle, type A personality, family history of MI in men under 45, women under 55 years of age
Clinical • A cute, severe, crushing chest pain, often radiating to the jaw or left arm; diaphoresis; little or no chest pain may
features be present in diabetic and elderly patients
• ECG: ST elevation and T-wave inversion with or without Q-waves
• Elevated cardiac enzymes
Prognosis • Sudden cardiac death: secondary to a fatal arrhythmia, occurs in 25%
• Mortality after myocardial infarction: 35% in the first year, 45% in second year, and 55% in third year
• Complications: arrhythmias, CHF, cardiogenic shock, systemic emboli from mural thrombi, aneurysm
• W all/papillary muscle rupture (3−7 days after infarct), postinfarction pericarditis (Dressler syndrome;
2–10 weeks postinfarction)
Treatment and • Coronary artery bypass: saphenous vein or internal mammary artery grafts restore circulation; grafts
management last approximately 10 years before restenosis typically occurs
• Angioplasty (balloon dilatation) also restores circulation, half re-stenose in 1 year
• F ibrinolytic therapy (e.g., tissue plasminogen activators): highly effective in reducing mortality if administered
early in the course of the MI.
256
►►Appearance of Infarcted Myocardium Cardiac Enzymes ORGAN SYSTEMS │ 2. The Cardiovascular System
Time Gross Histologic Troponin I peaks first (4 h): remains
elevated 7–10 days
1 hour No gross changes evident Intracellular edema
CK-MB peaks within 24 h: remains
6–12 hours Pale, cyanotic, edematous Wavy myocardial fibers, elevated 2–3 days
12–24 hours vacuolar degeneration,
contraction band necrosis, LDH peaks later (about 2 days): remains
beginning neutrophilic elevated 8–14 days
infiltrate
AST also rises and falls predictably in
24–48 hours Well-demarcated, soft, pale Neutrophilic infiltrate, myocardial infarction, but may indicate
increased cytoplasmic liver damage instead
eosinophilia, and
coagulation necrosis Definition of abbreviations: AST, aspartate
become evident aminotransferase; CK-MB, creatine kinase
MB fraction; LDH, lactate dehydrogenase.
3–10 days Infarct becomes soft, yellow, Monocytic infiltrate
surrounded by hyperemic rim predominates at 72 hours
2 weeks Infarct area is surrounded by granulation tissue that is gradually
replaced by scar tissue.
►►Rheumatic Fever and Rheumatic Heart Disease
Acute • Onset is typically 1–3 weeks after group A β-hemolytic streptococcal pharyngitis, otitis media
rheumatic fever • Children: 5–15 years old
• Declining incidence secondary to penicillin use
• Antistreptococcal antibodies cross-react with host connective tissue
• Diagnosed using Jones criteria (two major or one major and two minor)
Jones Criteria Major Minor
Mnemonic: • Migratory polyarthritislarge joints that become red, • Previous rheumatic fever
Jones swollen, and painful • Fever
• Arthralgias
♥ carditis • E rythema marginatummacular skin rash, often in “bathing • Prolonged PR interval
suit” distribution • Elevated ESR
Nodules • Leukocytosis
Erythema marginatum • S ydenham choreainvoluntary, choreiform movements of • Elevated C-reactive protein
Sydenham chorea the extremities
• Subcutaneous nodules
• Carditismay affect the endocardium, myocardium, or
pericardium; myocarditis causes most deaths during the acute
stage
Rheumatic • Repeated bouts of endocarditis and inflammatory insult lead to scarring and thickening of the
heart disease valve leaflets with nodules along lines of closure
• Mitral valve most commonly (75–80%) affected; fibrosis and deformity lead to “fish mouth” or “buttonhole”
stenosis. Next in frequency are the aortic and mitral valves together. Tricuspid and pulmonic valves are
rarely affected.
• Aschoff bodies are pathognomonic lesions; focal collections of perivascular fibrinoid necrosis surrounded
by inflammatory cells including large histiocytes (Anitschkow cells)
• Left atrial dilatation, mural thrombi, and right ventricular hypertrophy
• Predisposes to infective endocarditis
257
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Congestive Heart Failure (CHF)
Types Etiology Comments
Left-sided • Ischemic heart disease • Increased back pressure produces pulmonary congestion and edema
heart failure • Aortic stenosis • Dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and cough
• Aortic insufficiency • Renal hypoperfusion stimulates renin-angiotensin-aldosterone axis
• Hypertension • Retention of salt and water compounds the pulmonary edema
• Cardiomyopathies
• C hronic passive congestion of the liver (nutmeg liver),
Right-sided • Left-sided heart failure peripheral edema, ascites, jugular venous distension
heart failure • Cor pulmonale
• Pulmonary stenosis • Renal hypoperfusion with salt and water retention
• Pulmonary insufficiency
• Cor pulmonale is right ventricular failure, resulting specifically
Cor pulmonale • Parenchymal disease (e.g., COPD, from pulmonary hypertension
causing increased pulmonary vascu-
lar resistance) • May be acute (massive pulmonary embolus) or chronic.
• Vascular disease (e.g., vasculitis,
shunts, multiple emboli)
►► Shock
Decreased Effective Circulatory Volume
Causes • Decreased cardiac output (myocardial infarction, arrhythmia, tamponade)
• Reduction of blood volume (hemorrhage, adrenal insufficiency, fluid loss)
• Pooling in periphery: massive vasodilation caused by bacterial toxins and vasoactive substances
Complications • Cellular hypoxia, lactic acidosis
• Encephalopathy
• Myocardial necrosis and infarcts
• Pulmonary edema, adult respiratory distress syndrome
• Acute tubular necrosis
Stages Compensated: reflex tachycardia, peripheral vasoconstriction
Decompensated: ↓ blood pressure, ↑ tachycardia, metabolic acidosis, respiratory distress, and
↓ renal output
Irreversible: irreversible cellular damage, coma, and death
258
►►Endocarditis ORGAN SYSTEMS │ 2. The Cardiovascular System
Classic Signs
Janeway lesionserythematous, nontender lesions on palms and soles
Roth spotsretinal hemorrhages
Osler nodeserythematous, tender lesions on fingers and toes
(Also see anemia, splinter hemorrhages)
Acute • Organismhigh virulence; Staphylococcus aureus (50%) and streptococci (35%)
• Affects previously normal valves
• Often involves the tricuspid valve in intravenous drug users
• V egetations may form myocardial abscesses, septic emboli, or destroy the HACEK valve, causing
insufficiency.
• High fever with chills
Subacute bacterial • Organismlow virulence. Streptococcus viridans, gram-negative bacilli, Staphylococcus epidermidis,
endocarditis gram-negative bacilli (both are normal oral flora), Staphylococcus epidermidis (IV drug use)
Nonbacterial • Candida is a rare cause (associated with indwelling vascular catheters)
thrombotic (marantic) • Affects previously abnormal valves
endocarditis • More insidious onset, with positive blood cultures, fatigue, low-grade fever without chills, splinter
hemorrhages
• Associated with chronic illness
• Mitral valve most commonly affected
• Sterile, small vegetations, loosely adhering along lines of closure
• May embolize and provide a nidus for infective endocarditis
Nonbacterial • Mitral and tricuspid valvulitis in patients with systemic lupus erythematosus (SLE)
verrucous (Libman- • Small, warty vegetations on both sides of their valve leaflets
Sacks) endocarditis • Does not embolize and rarely provides a nidus for infection
►►Myocarditis
• M ay have dilatation and hypertrophy of all four chambers, diffuse or patchy pallor with foci of hemorrhage, peripheral edema
• Inflammatory lesions with characteristic cellular infiltrate:
Neutrophilicbacterial myocarditis
Mononuclearviral myocarditis
EosinophilicFiedler myocarditis
Noninfectious Collagen vascular diseases, rheumatic fever, SLE, and drug allergies
myocarditis
Viral myocarditis • Most common form of myocarditis
• Coxsackie B (positive-sense RNA viruses, picornavirus family); also, polio, rubella, and influenza
• Self-limited, but may be recurrent and lead to cardiomyopathy and death.
• 1/3 of AIDS patients show focal myocarditis on autopsy
Bacterial myocarditis Diphtheria (toxin-mediated), meningococci
Protozoal • Trypanosoma cruzi: Chagas disease; myocardial pseudocysts can lead to CHF
• Toxoplasmosis also causes pseudocysts
• Myocardial involvement appears days to weeks after the primary infection
• May be asymptomatic versus acute onset of dyspnea, tachycardia, weakness, or severe CHF
• Most recover fully
259
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Valvular Heart Disease
Mitral valve • Mitral leaflets (usually posterior) project into left atrium during systole, leading to insufficiency
prolapse • 7% of the United States population, most commonly in young women
• Seen in most patients with Marfan syndrome
• Characteristic midsystolic click and high-pitched murmur
• Usually asymptomatic, but may have associated dyspnea, tachycardia, chest pain
• Complications: atrial thrombosis, calcification, infective endocarditis, systemic embolization
Mitral stenosis • Stenosis may be combined with mitral valve prolapse
• Increased left atrial pressure and enlarged left atrium
• Early diastolic opening snap
• Complications: pulmonary edema, left atrial enlargement, chronic atrial fibrillation, atrial thrombosis
and systemic emboli
Aortic valve • Acute (infective endocarditis)
insufficiency • Sudden left ventricular failure, increased left ventricular filling pressure, inadequate stroke volume
• Chronic (aortic root dilation):
− Volume overload, eccentric hypertrophy
− Wide pulse pressure (bounding pulse)
− Etiologies include congenitally bicuspid aortic valve, rheumatic heart disease, or syphilis
Aortic valve • Rheumatic heart disease, bicuspid aortic valve
stenosis • Thickening and fibrosis of valve cusps without fusion of valve commissures (fusion present in
rheumatic heart disease)
• Asymptomatic until late, presents with angina, syncope, and CHF
• Systolic ejection click
• Complications: sudden death, secondary to an arrhythmia or CHF
►►C ardiomyopathies
Diseases Not Related to Ischemic Injury
Dilated (congestive) • Gradual dilatation of all four chambers, producing cardiomegaly, ↓ contractility, stasis, formation of
cardiomyopathy mural thrombi.
• Death from progressive CHF, thromboembolism, or arrhythmia
• E tiologies: idiopathic, alcohol (reversible), doxorubicin (irreversible), thiamine deficiency, pregnancy,
postviral
Hypertrophic • M arked asymmetric hypertrophy of the ventricular septum, left ventricular outflow obstruction
cardiomyopathy (idiopathic • Decreased cardiac output may cause dyspnea, angina, atrial fibrillation, syncope, sudden death
hypertrophic subaortic • Classic case: young adult athletes who die during strenuous activity
stenosis) • Etiologies: genetic (50%, autosomal dominant pattern)
Restrictive (infiltrative) • Diastolic dysfunction (impaired filling)
cardiomyopathy • Infiltration of extracellular material within myocardium
• E tiologies: elderlycardiac amyloidosis (may induce arrhythmias); young (<25 years old)
sarcoidosis associated with systemic sarcoidosis
• Secondary cardiomyopathy: metabolic disorders, nutritional deficiencies
260
►►Pericardial Disease ORGAN SYSTEMS │ 2. The Cardiovascular System
• Usually secondary; local spread from adjacent mediastinal structures
• Primary pericarditis is usually due to systemic viral infection, uremia, and autoimmune diseases
Fibrinous • Exudate of fibrin
pericarditis • Etiologies: post myocardial infarction, trauma, rheumatic fever, radiation, SLE
• Loud pericardial friction rub with chest pain, fever
Serous • Small exudative effusion with few inflammatory cells
pericarditis • Etiologies: nonbacterial, immunologic reaction (rheumatic fever, SLE), uremia, or viral
• Usually asymptomatic
Suppurative • Purulent exudate; leads to constrictive pericarditis and cardiac insufficiency
pericarditis • Etiologies: bacterial, fungal, or parasitic infection
• May have systemic signs of infection and a soft friction rub
Hemorrhagic • Exudate of blood with suppurative or fibrinous component
pericarditis • Etiologies: tuberculosis or a malignant neoplasm; organization
• May lead to constrictive pericarditis
Caseous • Caseous exudate with fibrocalcific constrictive pericarditis
pericarditis • Etiologies: tuberculosis
►►Pericardial Effusion
Pericardial effusion is leakage of fluid (transudate or exudate) into the limited pericardial space. It may result in cardiac tamponade.
Generally, the rate of filling rather than the absolute volume determines the degree of tamponade.
Serous effusion • Etiology: hypoproteinemia or CHF
• Develops slowly, rarely causing cardiac compromise
Serosanguineous • Etiology: history of trauma (e.g., cardiopulmonary resuscitation), tumor, or TB
effusion • Develops slowly, rarely causing cardiac compromise
Hemopericardium • Etiology: penetrating trauma, ventricular rupture (after myocardial infarction), or aortic rupture
• Develops quickly; can cause cardiac tamponade and death
►►Cardiac Neoplasms
Primary tumors Myxoma: most common primary cardiac tumor in adults
(rare, majority benign) • Most occur in the left atrium
• May be any size; sessile or pedunculated
• Complications include ball-valve obstructions of the mitral valve, embolization of tumor fragments
Rhabdomyoma: most common primary cardiac tumor in children (especially those with tuberous
sclerosis)
Metastases Lung and lymphoma, predominantly involving the pericardium
261
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Vasculitides
Disease Involvement Clinical Comments Treatment
Smoking cessation
Buerger disease • Involves small and Causes severe pain • Neutrophilic
medium-sized arteries (claudication) and Raynaud vasculitis that Corticosteroids,
(thromboangiitis and veins in the phenomenon in affected tends to involve the occasionally
obliterans) extremities extremity extremities of young immunosuppressants
men (usually under
• Microabscesses and Associated with bronchial 40) who smoke • Most patients
segmental thrombosis asthma, granulomas, and heavily treated with
lead to vascular eosinophilia supportive therapy
insufficiency, ulceration, • C ommon in Israel,
gangrene • T ypically develops after India, Japan, and • Usually self-limited
a URI South America • Cyclophosphamide
Churg-Strauss Lung, spleen, kidney
syndrome • “ Palpable purpura” skin • Variant of sometimes used in
(allergic • Affects small vessels, rash on buttocks and legs polyarteritis nodosa cases with severe
granulomatosis most commonly in IgA nephropathy
and angiitis) the skin, joints, and • A rthralgias • P-ANCA ⊕
gastrointestinal system • GI symptoms: abdominal IV immunoglobulin
Henoch- • Most common (IVIG), aspirin,
Schönlein pain, intestinal form of childhood sometimes
purpura hemorrhage, melena systemic vasculitis anticoagulants
• N ephritis in cases with IgA (peak at age 5)
Kawasaki disease • Segmental necrotizing nephropathy Prednisone and
vasculitis involves large, • IgA-mediated cyclophosphamide
(mucocutaneous medium-sized, and small • Fever leukocytoclastic to induce remission
lymph node arteries • Conjunctivitis vasculitis with or treat relapse;
syndrome) • E rythema and erosions of circulating IgA methotrexate or
• C oronary arteries immune complexes azathioprine to
commonly affected (70%) the oral mucosa maintain remission
• Generalized • L inked to HLA-
Microscopic • I nvolves small vessels B35 and human (Continued)
polyangiitis in a pattern resembling maculopapular skin rash parvovirus
Wegener granulomatosis, • Lymphadenopathy
but without granulomas • Mortality rate is 1–2% due Commonly affects
infants and young
• Resembles polyarteritis to rupture of a coronary children (age < 4) in
nodosa in some vessels aneurysm or coronary Japan, Hawaii, and
thrombosis U.S. mainland
• S egmental fibrinoid
necrosis of the media may • F ever, malaise, myalgia, • 8 0% are ANCA
be present weight loss positive, with 60%
P-ANCA positive
• S ome vessels show • Skin rash in 50%, and 40% C-ANCA
infiltration with including ulcerations positive
fragmented neutrophils = and gangrene
leukocytoclastic angiitis • Immune complexes
• Can affect vessels in are rare
many organ systems
• E tiology unclear
• R oughly ¾ of patients
survive 5 years
262
►►Vasculitides (Cont'd.) ORGAN SYSTEMS │ 2. The Cardiovascular System
Disease Involvement Clinical Comments Treatment
Polyarteritis • S mall and medium-sized • Affects young adults (male • H epatitis B antigen Corticosteroids and
nodosa arteries in skin, joints, > female) cyclophosphamide
peripheral nerves, kidney, (HBsAg) ⊕ in 30% (often fatal without
heart, and GI tract • L ow-grade fever, weight of cases treatment)
loss, malaise
• Lesions will be at different
stages (acute, healing, • H ematuria, renal failure,
healed) hypertension
• A bdominal pain, diarrhea,
GI bleeding
• Myalgia and arthralgia
Sturge Weber • Congenital vascular • S eizures and other • T hought to be • Laser therapy can
syndrome disorder affecting capillary- neurologic manifestations due to a failure ameliorate the port-
type vessels due to altered blood flow of regression of wine stain
(“vascular steal”) in brain embryonal vessels
• Angiomas of the adjacent to leptomeningeal that normally occurs • Medical treatment
leptomeninges and skin angiomas around the ninth of secondary
week of gestation conditions such as
• Cutaneous angiomas • Glaucoma, blindness seizures, glaucoma,
(port-wine stains) • Microscopically, and headaches
involving the skin of the • M ental deficiency may the port-wine stain,
face in the distribution be present which is a type of • S ome patients
of ophthalmic and nevus flammeus, require surgery for
maxillary divisions of • M ay have hemiparesis shows dilated and intractable seizures
trigeminal nerve contralateral to ectatic capillaries or other major
leptomeningeal neurologic problems
• L eptomeningeal angiomatosis
angiomatosis
Takayasu arteritis • G ranulomatous vasculitis • Fever, night sweats, Most common in Asia, Corticosteroids
with massive intimal muscle and joint aches, especially
(pulseless fibrosis that tends to loss of pulse in upper in young and middle-
disease) involve medium-sized to extremities aged women (ages
large arteries, including 15–45)
the aortic arch and major • May lead to visual loss
branches and other neurologic
abnormalities
• P roduces characteristic
narrowing of arterial orifices
Temporal arteritis • Usually segmental • Headache, facial pain, • M ost common form Corticosteroids
granulomatous involvement tenderness over arteries, of vasculitis (important to avoid
(giant cell of small and medium-sized and visual disturbances blindness)
arteritis) arteries, esp. the cranial (can progress to • A ssociated with
arteries (temporal, facial, blindness) HLA-DR4
and ophthalmic arteries)
• Fever, malaise, weight • P olymyalgia
• Multinucleated giant cells loss, muscle aches, rheumatica:
and fragmentation of the anemia systemic flu-like
internal elastic lamina symptoms; joint
seen in affected segments. • Patient usually middle- involvement also
aged to elderly female present
• Elevated ESR
Wegener • Necrotizing granulomatous • Middle-aged adults, males Associated with Corticosteroids,
granulomatosis vasculitis that affects small > females C-ANCA (autoantibody immunosuppressants
arteries and veins against
• Bilateral pneumonitis proteinase 3)
• Classically involves nose, with nodular and cavitary
sinuses, lungs, and pulmonary infiltrates
kidneys
• Chronic sinusitis
• N asopharyngeal
ulcerations
• Renal disease
(focal necrotizing
glomerulonephritis)
263
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Additional Vascular Diseases
Arteriolosclerosis
• Refers to small artery and arteriolar changes, leading to luminal narrowing that are most often seen in patients with diabetes, hypertension,
and aging
• Hyaline and hyperplastic (onion-skinning) types
Atherosclerosis
Characterized by lipid deposition and intimal thickening of large and medium-sized arteries. Abdominal aorta more likely involved than the
thoracic aorta. Within the abdominal aorta, lesions tend to be more prominent around the ostia. After the abdominal aorta, others commonly
affected are the coronary, popliteal, and internal carotid arteries.
Key process: intimal thickening and lipid accumulation produces atheromatous plaques
The earliest lesion is the fatty streak, which is seen almost universally in children and may represent reversible precursor. The progression
of the disease is thought in part due to a response to injury from such agents as hypertension, hyperlipidemia, and tobacco smoke. This
leads to inflammatory cell adherence, migration, and proliferation of smooth muscle cells from the media into the intima.
The mature plaque has a fibrous cap, a cellular zone composed of smooth muscle cells, macrophages, and lymphocytes and a
central core composed of necrotic cells, cholesterol clefts, and lipid-filled foam cells (macrophages). Complicated plaques are
seen in advanced disease. These plaques may rupture, form fissures or ulcerate, leading to myocardial infarcts, strokes, and mesenteric
artery occlusion. Damage to the cell wall predisposes to aneurysm formation.
Major Risk Factors Minor Risk Factors
Hyperlipidemia, hypertension, smoking, diabetes Male sex, obesity, sedentary lifestyle, stress, elevated
homocysteine, oral contraceptive use, increasing age, familial/
genetic factors
Mönckeberg Medial Calcific Sclerosis
Asymptomatic medial calcification of medium-sized arteries
Raynaud Disease
An idiopathic small artery vasospasm that causes blanching and cyanosis of the fingers and toes; the term Raynaud phenomenon is used
when similar changes are observed secondary to a systemic disease, such as scleroderma or systemic
lupus erythematosus.
264
►►Hypertension ORGAN SYSTEMS │ 2. The Cardiovascular System
Most cases (90%) are idiopathic and termed essential hypertension. The majority of the remainder is secondary to intrinsic renal
disease; less commonly, narrowing of the renal artery. Infrequent secondary causes include primary aldosteronism, Cushing disease,
and pheochromocytoma.
Renal causes of hypertension can usually be attributed to increased renin release. This converts angiotensinogen to angiotensin I, which is
converted to angiotensin II in the lung. Angiotensin II causes arteriolar constriction and stimulates aldosterone secretion
and therefore sodium retention, which leads to an increased intravascular volume.
Classification of Blood Pressure for Adults*
BP Classification Systolic BP (mm Hg) Diastolic BP (mmHg)
Normal < 120 and < 80
Prehypertension 120-139 or 80-89
Stage 1 Hypertension 140-159 or 90-99
Stage 2 Hypertension ≥ 160 or ≥ 100
* Guidelines from 7th Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)
►►Aneurysm
• A congenital or acquired weakness of the vessel wall media, resulting in a localized dilation or outpouching
• Complications: thrombus formation, compression of adjacent structures, and rupture with risk of sudden death
Type of Aneurysm Associations Anatomic Location Comments
Atherosclerotic Atherosclerosis, hypertension Usually involve abdominal Half of aortic aneurysms
aorta, often below renal >6 cm in diameter will rupture
arteries within 10 years
Syphilitic Syphilitic obliterative endarteritis of Ascending aorta (aortic root) May dilate the aortic valve ring,
vasa vasorum causing aortic insufficiency
Marfan syndrome Lack of fibrillin leads to poor Ascending aorta (aortic root) May dilate the aortic valve ring,
elastin function causing aortic insufficiency
Dissecting aneurysm Hypertension, cystic medial Blood enters intimal tear Presents with severe tearing
(aortic dissection) necrosis (e.g., Marfan syndrome) in aortic wall and spreads pain
through media
Berry aneurysm Congenital; some associated with Classic location: Circle of Rupture leads to subarachnoid
adult polycystic kidney disease Willis hemorrhage
►►Venous Disease Involves deep leg veins Major complication: pulmonary embolus
Deep vein thrombosis Dilated, tortuous veins caused by increased • Superficial veins of legs
Varicose veins intraluminal pressure • Hemorrhoids
• Esophageal varices
265
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Vascular Tumors
Angiosarcoma • Malignant vascular tumor with a high mortality
• Occurs most commonly in skin, breast, liver, soft tissues
Glomus tumor • Small, painful tumors most often found under fingernails
Hemangioma • Common, benign tumors that may involve skin, mucous membranes, or internal organs
Hemangioblastoma • Associated with von Hippel-Lindau disease
• Tends to involve the central nervous system and retina
Kaposi sarcoma • Low-grade malignancy of endothelial cells
• Viral etiology: human herpesvirus 8 (HHV8)
• Most often seen in AIDS patients in the U.S.
►►Edema and Shock
Edema • Fluid is maintained with vessels via balance between hydrostatic pressure (“pushing fluid out”)
and oncotic pressure (“pulling fluid in”).
• Most causes of edema can be related to either increased hydrostatic pressure or reduced plasma osmotic
pressure. Other causes included lymphatic obstruction, sodium retention.
• C linically, may see pitting edema in extremities (dependent) or massive generalized edema (anasarca).
Increased Hydrostatic Pressure Reduced Plasma Osmotic Pressure
Local: deep vein thrombosis Cirrhosis, nephrotic syndrome, protein losing enteropathy
Generalized: congestive heart failure
Shock Three major variants: cardiogenic, septic, and hypovolemic
Type Comments Heart Rate Systemic Cardiac
Vascular Output
Resistance
Cardiogenic Intrinsic pump failure. As the heart fails, stroke volume ↑ ↑ ↓
decreases, with compensatory increases in heart rate
and systemic vascular resistance.
Septic Endotoxin mediated. Massive peripheral vasodilation ↑ ↓ ↑
with a decrease in systemic vascular resistance. There
is peripheral pooling of blood (decreased effective
circulatory volume). The heart compensates with an
increase in heart rate.
Hypovolemic Blood loss. The effective circulatory volume decreases ↑ ↑ Unchanged
through actual loss. The heart is able to attempt to
compensate with an increase in heart rate.
266
Cardiovascular Pharmacology ORGAN SYSTEMS │ 2. The Cardiovascular System
►►Antiarrhythmic Drugs
Drugs Mechanism of Effect Indications Toxicities Notes
Action
Class I: Na+ Channel Blockers (Local Anesthetics)
These agents block the open or inactivated channel preferentially and therefore block frequently depolarized (e.g., abnormal) tissue
better (use dependence; state dependence). Class I drugs are subdivided into three groups based on their effect on AP duration.
Class IA • ↓ Na+ influx • ↓ K+ efflux (↑ Atrial and • Quinidine: cinchonism • H yperkalemia
AP duration, ventricular (headache, tinnitus, enhances
quinidine • S lows phase 0 ↑ ERP, slows arrhythmias vertigo), ↑ QT interval, cardiotoxic
procainamide depolarization conduction) torsades de pointes, effects
disopyramide in His-Purkinje autoimmune reactions (e.g.,
fibers and cardiac thrombocytopenia) • Quinidine
muscle enhances
• P rocainamide: reversible digoxin toxicity
SLE-like syndrome
Class IB • ↓ Na+ influx • ↓ AP Ventricular CNS toxicity Hyperkalemia
in ischemic or duration arrhythmias enhances
lidocaine depolarized (e.g., post MI, cardiotoxic effects
mexiletine Purkinje and • Prolongs digitalis toxicity)
tocainide ventricular tissue diastole
(little effect on
atrial or normal
tissue)
• Shortens phase 3
repolarization
Class IC • ↓ Na+ influx • No effect on Refractory Proarrhythmic Can precipitate
AP duration ventricular cardiac arrest
flecainide • M arkedly arrhythmias and sudden
propafenone slows phase 0 • S lows (used as last death in patients
encainide depolarization conduction resort) with preexisting
in His-Purkinje velocity cardiac
fibers and cardiac abnormalities
muscle • Increase QRS
duration
Class II: Beta Blockers
These drugs slow AV conduction.
propranolol • β -adrenoreceptor • ↓ AV node • SVT Impotence, bradycardia, • Used post MI;
metoprolol blockade conduction depression, worsens asthma has a protective
esmolol • P ost-MI effect
− ↓ cAMP • ↑ PR interval arrhythmia
− ↓ Ca2+ current prophylaxis • May mask
premonitory
• ↓ phase 0 signs of
depolarization in hypoglycemia
AV node
• E smolol-very
• ↓ phase 4 short acting
depolarization in
SA node
(Continued)
267
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Antiarrhythmic Drugs (Cont'd.)
Drugs Mechanism of Effect Indications Toxicities Notes
Action • S otalol: also
Class III: K+ Channel Blockers class II
These agents prolong the AP and increase the ERP.
sotalol ↓ K+ current (delayed • ↑ AP Atrial fibrillation/ • General: torsade de
ibutilide rectifier current), duration flutter, pointes, sinus bradycardia
dofetilide prolonging phase ventricular
amiodarone 3 repolarization • ↑ERP arrhythmias, • A miodarone: pulmonary
of AP refractory fibrosis, hepatotoxicity,
arrhythmias cutaneous,
photosensitivity, corneal
deposits, thyroid dysfunction
• Bretylium: new arrhythmias,
↓ BP
• Sotalol: excessive β
blockade
Class IV: Ca2+ Channel Blockers
By blocking L-type Ca2+ channels, these agents slow AV node conduction.
verapamil Block L-type Ca2+ Decreased • Atrial Constipation, dizziness,
diltiazem channels conductivity fibrillation/ flushing, AV block, strong
SA/AV nodes flutter negative inotropic effect,
hypotension
• Atrial
automaticities
• A V nodal
reentry
Unclassified
Adenosine: used for AV nodal arrhythmias; extremely short acting
Mg2+: used in digitalis-induced arrhythmias, torsade de pointes
K+: used in digitalis-induced arrhythmias; ↓ other ectopic pacemakers
Digoxin: used in rapid atrial flutter/fibrillation, AV nodal reentrant arrhythmias
268
►►Antihypertensives ORGAN SYSTEMS │ 2. The Cardiovascular System
Class Drugs Mechanism Side Effects/Notes
SYMPATHOPLEGICS
α1 antagonists Prazosin Block α1 receptors on Orthostatic hypotension and syncope, especially with the
α2 agonists Doxazosin arterioles and venules first dose
Terazosin
Decrease sympathetic Rebound hypertension, dry mouth, sedation,
Clonidine outflow by stimulating α2 bradyarrhythmias
receptors in the CNS
Methyldopa Sedation, hemolytic anemia; it is a prodrug that is
Block postsynaptic β converted to α-methyl norepinephrine
β blockers Propranolol receptors
Atenolol CV disturbances, impotence, sleep disturbances,
Postganglionic Metoprolol, others sedation, asthma
sympathetic Reserpine
terminal blockers Destroys adrenergic Rarely used; depression, sedation, dry mouth, edema,
Guanethidine synaptic vesicles, bradycardia, night terrors
decreasing NE release
Depletes NE and blocks Rarely used; orthostatic hypotension, sexual dysfunction;
NE release uses uptake site to enter nerve terminal
Ganglionic Hexamethonium Ganglionic nicotinic Rarely used; side effects result from blocking both
blockers Mecamylamine antagonists that inhibit sympathetic and parasympathetic tone
postganglionic sympathetic
neurons
VASODILATORS
Ca2+ channel Amlodipine Block L-type Ca2+ channels Constipation, edema, headache, bradycardia, GI
blockers Diltiazem in cardiac and smooth disturbances, dizziness, AV block, CHF, tachycardia
Nifedipine muscle (nifedipine)
Drugs acting Verapamil
through nitric Hydralazine Release endothelial NO Reversible lupus erythematosus-like syndrome, edema;
oxide (NO) → stimulation of smooth arteriolar dilation
Nitroprusside muscle guanylate cyclase
Drugs acting → ↑ cGMP For hypertensive emergencies, arteriolar and venous
by opening K+ Minoxidil dilation; cyanide poisoning
channels
Diazoxide Open K+ channels → For severe hypertension; hirsutism, pericardial effusion,
D1 agonist Fenoldopam hyperpolarization of edema
vascular smooth muscle
For hypertensive emergencies; hypoglycemia
Vasodilate renal vessels For hypertensive emergencies
INHIBITORS OF ANGIOTENSIN
Angiotensin- Captopril Block formation of Dry cough, hyperkalemia, angioedema, renal damage in
converting Enalapril angiotensin II, leading also preexisting renal disease; contraindicated in pregnancy
enzyme inhibitors Fosinopril to a ↓ in aldosterone (fetal renal damage)
(ACEIs) Ramipril
Lisinopril
Angiotensin II Losartan Block angiotensin II at AT1 Renal damage in preexisting renal disease,
receptor blockers Valsartan receptor; ↓ in aldosterone hyperkalemia; contraindicated in pregnancy (fetal renal
(ARBs) Candesartan damage)
↓ angiotensin I (and Hyperkalemia
Renin inhibitor Aliskiren therefore ATII and
aldosterone) (Continued)
269
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Antihypertensives (Cont’d.)
Class Drugs Mechanism Side Effects/Notes
DIURETICS
Thiazides Hydrochlorothiazide Inhibit Na+/Cl- transporter Useful in mild hypertension; ↓ K+, ↓ Mg2+, ↑ Ca2+, ↓ Na+,
Loop diuretics Metolazone ↑ uric acid, ↑ glucose, ↑ LDL cholesterol, ↑ triglycerides
Furosemide Inhibit Na+/K+/2Cl-
Aldosterone transporter Used in moderate to severe hypertension; ↓ K+, ↓ Mg2+,
antagonists Spironolactone ↓ Ca2+, ↓ Na+, ↑ uric acid, ↑ glucose, ↑ LDL cholesterol,
Aldosterone antagonist in ↑ triglycerides
the distal convoluted tubule
Hyperkalemia, metabolic acidosis, gynecomastia; can be
safely used in pregnancy
Concomitant Disease States
Disease State Agents Initially Agents Contraindicated Other Notes
Indicated
Pregnancy Methyldopa ACE; ARB
Hydralazine
Diabetes ACEI, ARB BB (high dose) Additional treatment with lower-dose BB is
acceptable. Diuretics are also good secondary
agents
Heart Failure ACEI BB (high dose), verapamil; Additional treatment with BB (low dose), ARB,
diltiazem diuretics (all classes); can use select CBs
(amlodipine, felodipine)
COPD / Asthma CB BB (Non-selective high ACE not recommended due to chronic cough
dose) side effect
Chronic Kidney ACEI, ARB Loop diuretics can be used; do not use other
Disease diuretics in renal insufficiency
Benign Prostatic Alpha blockers
Hypertrophy
Severe Depression BB, reserpine, methyldopa
Post-MI BB, spironolactone, ACEI also acceptable
verapamil, diltiazem
Recurrent Stroke Diuretics, ACEI
Prevention
Definition of Abbreviations: ACEI, Angiotensin-Converting Enzyme Inhibitor; ARB, Angiotensin Receptor Blocker; BB, Beta Blocker;
CB, Calcium Channel Blocker
270
►►Antianginal Drugs ORGAN SYSTEMS │ 2. The Cardiovascular System
Angina pectoris, the primary symptom of ischemic heart disease, occurs in periods of inadequate oxygen delivery to the myocardium.
Classically, this symptom is described as a crushing, pressure-like pain that occurs during periods of exertion. Strategies used to treat this
condition include:
− increasing oxygen delivery through increased perfusion
− decreasing myocardial oxygen demands
Drug Class
Nitrates Calcium Channel Blockers Beta blockers
(nitroglycerin, isosorbide dinitrate) (nifedipine, verapamil, diltiazem) (propranolol, atenolol, metoprolol)
Molecular Generation of endothelial NO Inhibits voltage-gated “L-type” Ca2+ β-adrenergic antagonism
mechanism activates GC → ↑ cGMP → channels and ↓ Ca2+ influx in cardiac
dephosphorylates MLCK → and vascular smooth muscle → ↓ muscle
relaxation of vascular smooth contractility
muscle
Physiologic • V enodilation → ↓ preload → ↓ • Arteriolar vasodilation → ↓ afterload ↓ contractility, ↓ HR, ↓ BP (mild),
mechanism afterload • ↓ myocardial O2 demand AmVyoncoadredicaol nOd2udcetimonanvedl,ocity
• ↓ AV node conduction velocity ↓
Indications • ↓ myocardial O2 demand ↓
Angina, HTN, SVT (except nifedipine)
Acute angina (nitroglycerin), Angina, HTN, arrhythmia
pulmonary edema
Adverse Reflex tachycardia, orthostatic Cardiac depression, peripheral edema, Impotence, depression,
effects hypotension, headache, constipation bradycardia
tachyphylaxis
Notes Contraindicated in patients taking Selectivity for vascular Ca2+ channels: Non-CV indications include
sildenafil → hypotension and Nifedipine > diltiazem > verapamil migraine, familial tremor, stage
sudden death fright, thyrotoxicosis, glaucoma;
Verapamil primarily affects myocardium beta blockers with ISA are
contraindicated in angina/MI
patients
Definition of abbreviations: AV, atrioventricular; cGMP, cyclic guanosine monophosphate; GC, guanylate cyclase; HTN, hypertension;
ISA, intrinsic sympathomimetic activity; SVT, supraventricular tachycardia.
►►Drugs Used in Heart Failure
Heart failure results when tissue demands for circulation cannot be met by an ailing myocardium. Inadequate cardiac output secondary
to decreased contractility leads to decreased exercise tolerance and muscle fatigue. Neurohumoral responses to this physiologic
shortcoming play an integral role in the pathogenesis of heart failure; thus, drugs used to treat this condition may be aimed at these
responses. Physiologically, these drugs may reduce afterload, reduce preload, or increase contractility.
Drug Class Mechanism of Action Effects Indications Toxicities Notes
ACE inhibitors Inhibits angiotensin- • D ecreased • CHF Dry cough, • Cornerstone of CHF
converting enzyme aldosterone → • Post-MI hypotension, therapy
captopril (ACE) → ↓ angiotensin ↓ fluid retention proteinuria,
enalapril II and ↑ bradykinin to prevent fetal renal • Prophylactic in
lisinopril • Vasodilation → pathologic toxicity, post-MI because
↓ preload and remodeling angioedema they oppose
Cardiac Inhibits Na+/K+ afterload • Hypertension “remodeling” that
glycosides ATPase → • Chronic renal Yellow vision, leads to heart
↑ intracellular Na+ → • Increased myocardial disease nausea, failure
digoxin ↓ Na+ gradient → Ca2+ → increased vomiting,
↓ Na+-Ca2+ exchange contractility • C HF (because diarrhea, • Hypokalemia
→ ↑ intracellular Ca2+ ↑ contractility) anorexia, enhances toxicity
• Delayed conduction hallucination,
at AV node. • Atrial fibrillation life- • Q uinidine →
(parasympathomimetic (because ↓ AV threatening ↑ dig toxicity
effect) conduction) arrhythmias (↓ dig clearance)
• D igoxin antibodies
(FAb fragments)
used in overdose
• D igoxin does not
improve survival
following MI
(Continued)
271
ORGAN SYSTEMS │ 2. The Cardiovascular System ►►Drugs Used in Heart Failure (Cont’d.)
Drug Class Mechanism of Action Effects Indications Toxicities Notes
Angiotensin Block angiotensin II Same as ACE inhibitors Same as ACE Fetal renal Not as well studied as
II−receptor receptors inhibitors toxicity, ACEIs, but seem to
blockers have same efficacy
no cough
losartan
candesartan
Vasodilators ↑ nitric oxide → cGMP Nitroglycerin, isosorbide CHF, HTN, Tachycardia, • Nitroprusside,
→ vasodilation dinitrate: angina, headache nitroglycerin
nitroglycerin pulmonary edema hypotension (extended release):
nitroprusside predominantly used in acute HF
isosorbide venodilators
• Hydralazine,
dinitrate Nitroprusside: dilation isosorbide dinitrate:
hydralazine of arteries = veins used in chronic HF
Beta-receptor These agents were once contraindicated in heart failure; now they are used to reduce the progression of mild to
antagonists moderate heart failure.
carvedilol • Carvedilol, labetalol: nonselective β antagonist, α1 antagonist
labetalol • Metoprolol: β1 antagonist
metoprolol • Contraindicated in patients with asthma or severe bradycardia
Beta-1 Used in acute heart failure
agonists Dopamine: ↓ dose → improves renal blood flow; moderate dose: stimulates myocardial contractility; ↑ doses →
dobutamine vasoconstrictor (alpha1 receptors); used for cardiogenic shock
dopamine Dobutamine: β1 selective
Diuretics Used to reduce symptoms of fluid retention (pulmonary congestion, edema); loop diuretics most effective, thiazides
can be effective in mild cases
►►Antihyperlipidemics
Drug Class/Agents Mechanism Side Effects/Comments
• Myalgia, myopathy (check creatine kinase)
HMG-CoA Reductase Inhibit rate-limiting step in cholesterol synthesis • R habdomyolysis
Inhibitors • ↑ serum aminotransferases
↓ Liver cholesterol • Teratogenic
(“-statins”: lovastatin, ↑ LDL-receptor expression • P 450 inhibitors can ↑ risk of hepatotoxicity,
atorvastatin, fluvastatin ↓ LDL
pravastatin, simvastatin, ↑ HDL myopathy
rosuvastatin,) ↓ VLDL synthesis
↓ Triglycerides • G I disturbances
• M alabsorption of lipid-soluble vitamins
Bile Acid Sequestrants ↓ Enterohepatic recirculation of bile salts, leading • ↓ Absorption of drugs (e.g., warfarin, thiazides,
(cholestyramine, colestipol, to:
colesevelam) digoxin, pravastatin, fluvastatin)
↑ Synthesis of new bile salts by liver
↓ Liver cholesterol Flushing (↓ by aspirin and over time), pruritus,
↑ LDL-receptor expression hepatoxicity
↓ LDL
• G allstones
Niacin Liver: ↓ VLDL synthesis • Myopathy (especially when combined with
Adipose tissue: ↓ lipolysis
↓ VLDL reductase inhibitors)
↓ LDL • C an ↑ LDL in some patients, so often combined
↑ HDL
↓ Triglycerides with other cholesterol-lowering agents
Fibrates Ligands for PPAR-α → activation of lipoprotein Possible ↑ of hepatotoxicity with reductase
(gemfibrozil, fenofibrate) lipases inhibitors
↓ Triglycerides
↓ VLDL and IDL
Modest ↓ LDL
Ezetimibe Blocks intestinal absorption of cholesterol
↓ LDL
272
The Respiratory System
Chapter 3
Respiratory Embryology and Histology Respiratory Pathology
Development of the Respiratory System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274 Ear, Nose, Throat, and Upper Respiratory System Infections . . . . . . . . . . . . 289–290
The Alveoli and Blood-Gas Barrier . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274 Middle Respiratory Tract Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291–292
Gross Anatomy Granulomatous Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
Obstructive Lung Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293–294
Pharynx and Related Areas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275 Drugs for Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294
The Larynx . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275 Restrictive Lung Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295
Intrinsic Muscles of the Larynx . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275 Respiratory Distress Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .295
Pleura and Pleural Cavities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276 Tumors of the Lung and Pleura . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296
Diseases of the Pleura . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
Respiratory Physiology Pulmonary Vascular Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
Lung Volumes and Capacities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
Dead Space and Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277–278
Mechanics of Breathing
Muscles of Breathing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
Elastic Properties of the Lung . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
Elastic Properties of the Lung and Chest Wall . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
Surface Tension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
Airway Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
The Breathing Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
Pulmonary Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
Summary of Classic Lung Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
Gas Exchange
Partial Pressures of O2 and CO2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
Diffusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283
Oxygen Transport and the Hemoglobin–O2 Dissociation Curve . . . . . . . . . . . . . 284
Additional Changes the Hemoglobin–O2 Dissociation Curve . . . . . . . . . . . . . . . 284
CO2 Transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
Pulmonary Blood Flow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
Ventilation-Perfusion Relationships . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286
Disorders That Affect Arterial Oxygen Pressure or Content . . . . . . . . . . . . . . . . . 287
Control of Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
Chemoreceptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
Response to High Altitude . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
273
ORGAN SYSTEMS │ 3. The Respiratory System Respiratory Embryology and Histology
►►Development of the Respiratory System
The respiratory (laryngotracheal) diverticulum forms
in the ventral wall of the foregut. The lung bud forms at
the distal end of the diverticulum and divides into two
bronchial buds. These branch into the main bronchi,
lobar bronchi, and segmental bronchi. The right bud
divides into three main bronchi, and the left divides into
two.
The tracheoesophageal septum divides the foregut into
the esophagus and trachea.
Clinical Correlate
A tracheoesophageal fistula is an abnormal communication between the trachea and esophagus caused by a malformation of the
tracheoesophageal septum. 90% occur between the esophagus and distal third of the trachea. It is generally associated with
esophageal atresia and polyhydramnios. Symptoms include gagging and cyanosis after feeding and the reflux of gastric contents
into the lungs, causing pneumonitis.
►►The Alveoli and Blood-Gas Barrier
Type I cell Alveolar The conducting zone of the lungs does not participate
macrophage in gas exchange and is anatomic dead space. It is
Alveolar composed of the trachea, bronchi, bronchioles, and
macrophage Connective terminal bronchioles. The trachea and bronchi contain
tissue pseudostratified ciliated columnar cells and goblet cells
Alveolus (secrete mucous). Bronchioles and terminal bronchioles
Type II cells contain ciliated epithelial cells and Clara cells (which
Capillary Endothelial cell secrete a surfactant-like substance, aid in detoxification,
Alveolus and are stem cells for the ciliated cells).
Capillary Red blood cell
The respiratory zone carries out gas exchange and
Type I cell consists of respiratory bronchioles, alveolar ducts, and
Basal lamina alveoli.
Endothelial cell
Terminal bronchioles divide into respiratory bronchioles,
which contain alveoli and branch to form alveolar ducts.
The ducts terminate in alveolar sacs and are lined by
squamous alveolar epithelium.
Alveoli are thin-walled sacs responsible for gas exchange.
They contain:
• T ype I epithelial cells, which provide a thin surface
for gas exchange.
• Type II epithelial cells, which produce surfactant.
• Alveolar macrophages, which are derived from
monocytes and remove particles and other irritants via
phagocytosis.
There are approximately 300 million alveoli in each lung.
274
Gross Anatomy ORGAN SYSTEMS │3. The Respiratory System
►►Pharynx and Related Areas
The pharynx is a passageway shared by the digestive and respiratory systems. It has lateral, posterior, and medial walls throughout but
is open anteriorly in its upper regions (nasopharynx, oropharynx), communicating with the nasal cavity and the oral cavity.
The nasopharynx is the region of the pharynx located directly posterior to the nasal cavity. It communicates with the nasal cavity
through the choanae (i.e., posterior nasal apertures).
The oropharynx is the region of the pharynx located directly posterior to the oral cavity. It communicates with the oral cavity through
a space called the fauces. The fauces are bounded by two folds, consisting of mucosa and muscle, known as the anterior and
posterior pillars.
• The anterior pillar of the fauces, also known as the palatoglossal fold, contains the palatoglossus muscle.
• The posterior pillar of the fauces, also known as the palatopharyngeal fold, contains the palatopharyngeus muscle.
• The tonsillar bed is the space between the pillars that houses the palatine tonsil.
The laryngopharynx is the region of the pharynx that surrounds the larynx. It extends from the tip of the epiglottis to the cricoid
cartilage. Its lateral extensions are known as the piriform recesses.
►►The Larynx
Thyroid cartilage Lateral The larynx is the voice box. It also maintains a patent airway and acts
Vocalis muscle arytenoid as a sphincter during lifting and pushing.
Vocal ligament muscle
Thyroarytenoid Action of lateral Skeleton of the larynx:
muscle (↓ tension) cricoarytenoid muscle
Posterior (adduction of vocal ligament) • Three unpaired laryngeal cartilages (i.e., thyroid, cricoid, epiglottis)
cricoarytenoid and three paired cartilages (i.e., arytenoid, cuneiform, corniculate)
muscle
• The fibroelastic membranes include the thyrohyoid membrane and the
Action of posterior cricothyroid membrane (conus elasticus).The free, upper border of the
cricoarytenoid muscle latter is specialized to form the vocal ligament on either side.
(abduction of vocal ligament)
Corniculate Hyoid bone Cricothyroid
cartilage Thyroid cartilage muscle (↑ tension)
Arytenoid Cricoid cartilage
cartilage Trachea
Transverse
arytenoid
muscle
Posterior
cricoarytenoid
muscle
Posterior Lateral
►►Intrinsic Muscles of the Larynx*
Muscle Function
Posterior cricoarytenoid Abducts vocal fold
Lateral cricoarytenoid Adducts vocal fold
Cricothyroid Tenses vocal fold
Thyroarytenoid (including vocalis) Relaxes vocal fold
Thyroepiglotticus Opens laryngeal inlet
Aryepiglotticus Closes laryngeal inlet
Oblique and transverse arytenoids Close laryngeal inlet
*N ote that the cricothyroid is innervated by the external laryngeal nerve, a branch of the superior laryngeal branch of the vagus nerve.
All other intrinsic laryngeal muscles are supplied by the recurrent laryngeal branch of the vagus nerve.
275
ORGAN SYSTEMS │ 3. The Respiratory System ►►Pleura and Pleural Cavities
Parietal pleura lines the inner surface of the thoracic cavity; visceral pleura follows the contours of the lung itself. Inflammation of the
central part of the diaphragmatic pleura may produce pain referred to the shoulder (phrenic nerve; C3, C4, and C5).
Costomediastinal
recess
Right lung Left lung Anterior view
Superior lobe Superior lobe
Middle lobe
Inferior lobe Inferior lobe
Costodiaphragmatic Diaphragm Mediastinum Costodiaphragmatic
recesses recess
Posterior view
• The costal line of reflection is where the costal pleura becomes continuous with the diaphragmatic pleura from Rib 8 in the
midclavicular line, to Rib 10 in the midaxillary line, and to Rib 12 lateral to the vertebral column.
• Costodiaphragmatic recesses are spaces below the inferior borders of the lungs where costal and diaphragmatic pleurae are in
contact.
• The costomediastinal recess is a space where the left costal and mediastinal parietal pleurae meet, leaving a space due to the
cardiac notch of the left lung. This space is occupied by the lingula of the left lung during inspiration.
Structure of the Lungs
• The right lung is divided by the oblique and horizontal fissures into three lobes: superior, middle, and inferior.
• The left lung has only one fissure, the oblique, which divides the lung into upper and lower lobes. The lingula of the upper lobe
corresponds to the middle lobe of the right lung.
• B ronchopulmonary segments of the lung are supplied by the segmental (tertiary) bronchus, artery, and vein. There are 10 on the
right and eight on the left.
Arterial Supply
• R ight and left pulmonary arteries arise from the pulmonary trunk. The pulmonary arteries deliver deoxygenated blood to the lungs
from the right side of the heart.
• Bronchial arteries supply the bronchi and nonrespiratory portions of the lung. They are usually branches of the thoracic aorta.
Venous Drainage
• There are four pulmonary veins: superior right and left and inferior right and left.
• Pulmonary veins carry oxygenated blood to the left atrium of the heart.
• The bronchial veins drain to the azygos system. They share drainage from the bronchi with the pulmonary veins.
Lymphatic Drainage
• Superficial drainage is to the bronchopulmonary nodes; from there, drainage is to the tracheobronchial nodes.
• Deep drainage is to the pulmonary nodes; from there, drainage is to the bronchopulmonary nodes.
• Bronchomediastinal lymph trunks drain to the right lymphatic and the thoracic ducts.
Innervation of Lungs
• Anterior and posterior pulmonary plexuses are formed by vagal (parasympathetic) and sympathetic fibers.
• Parasympathetic stimulation has a bronchoconstrictive effect.
• Sympathetic stimulation has a bronchodilator effect.
276
Respiratory Physiology ORGAN SYSTEMS │3. The Respiratory System
►►Lung Volumes and Capacities
Vt Tidal Air inspired and expired in normal breathing
volume
6
TLC Total lung Volume in lungs with maximal inspiration
capacity
5 FRC Functional Volume in lungs at end of quiet, passive expiration; the
Inspiratory residual equilibrium point of the system
reserve Inspiratory Total capacity
4 volume capacity lung
capacity RV Residual Volume at end of maximal forced expiration
Vital volume
3 capacity
Liters VC Vital Volume expired from maximal inspiration to maximal
Tidal
capacity expiration
volume
2 Expiratory IRV Inspiratory The volume inspired with a maximal inspiratory effort in
reserve volume
reserve excess of the tidal volume
1 Functional ERV volume The volume expelled with an active expiratory effort after
Residual residual capacity Expiratory
volume
0 reserve passive expiration
volume
IC Inspiratory The volume of air inspired with a maximal inspiratory
capacity effort after passive expiration
Note: FRC and RV cannot be measured with a spirometer. Spirometry can only
measure changes in volume.
►►Dead Space and Ventilation
VT = 500 ml
VD End of Inspiration Vd = dead space (no gas Standard Symbols
VD = 150 ml exchange)
a = alveolar
VA = VT - VD Anatomic Vd = conducting
airways a = arterial
VA VA = 350 ml
Contains CO2 Alveolar Vd = alveoli with poor V = volume
blood flow (ventilated but not V• = minute ventilation
perfused)
P = pressure
Physiologic Vd = anatomic +
alveolar dead space Paco2 = alveolar pressure of CO2
Paco2 = arterial pressure of CO2
Peco2 = Pco2 in expired air
Abbreviation Name Definition Normal Values
Vd 150 mL
Va Dead space Volume that does not exchange gas with blood 350 mL
Vt 500 mL
Alveolar volume Portion of tidal volume that reaches alveoli during inspiration
n 15/min
V• e Tidal volume: Amount of gas inhaled and exhaled during normal breathing 7,500 mL/min
Vt = Va + Vd – the sum of dead space volume and alveolar volume
(Continued)
Respiratory frequency Breaths/minute
Total ventilation: Total ventilation per minute
VV•etn==V•Vaa+n V+• dVdn
VV• etn==5(,325500 mL × 15/min) + (150 mL × 15/min) = 7,500 mL/min
mL/min + 2,250 mL/min = 7,500 mL/min
277
ORGAN SYSTEMS │ 3. The Respiratory System ►►Dead Space and Ventilation (Cont’d.)
V• a AV • lave=o(laVrtv–enVtdila) t×ionn Amount of inspired air that reaches the alveoli each minute. 5,250 mL/min
It is the effective part of ventilation.
V• a = V• co2 ×K The adequacy of alveolar ventilation can be determined from
Pco2 t•h e V•ccoon2c=enCtrOa2tiopnroodfuecxtipoinre(dgecnaerbraolnlydaiosxsiudme.e is normal and
constant)
• ↑ alveolar ventilation → ↓ Paco2
• ↓ alveolar ventilation → ↑ Paco2
Physiologic Dead Space
VD = PaCO2 − PECO2 All expired CO2 comes from alveolar gas, not from dead space gas. Therefore, the fraction shows the dilution
VT PaCO2 of CO2 by the dead space. In the normal individual, anatomic dead space = physiologic dead space, and Vd/
Vt = 0.2−0.35. In lung disease, this number can increase.
� Mechanics of Breathing
►►Muscles of Breathing
Muscles of • Diaphragm—most important
inspiration • O ther muscles of inspiration are used primarily during exercise or in diseases that increase airway resistance (e.g.,
asthma):
− External intercostal muscles (move ribs upward and outward)
− Accessory muscles (elevate first two ribs and sternum)
Muscles of • Expiration is passive during quiet breathing.
expiration • Muscles of expiration are used during exercise or increased airway resistance (e.g., asthma):
− Abdominal muscles (help push diaphragm up during exercise or increased airway resistance)
− Internal intercostal muscles (pull ribs downward and inward)
►►Elastic Properties of the Lung
Pressure-Volume Curve
Lung Compliance
6,000
Change of lung volume (ml) 5,000 Normal Distress Syndrome • Compliance (∆V/∆P) is used to estimate the distensibility of the lungs.
Emphysema4,000 It is inversely related to elasticity (tendency of a material to recoil when
3,000 Respiratory stretched).
2,000
1,000 • T he steeper the slope, the higher the compliance. The flatter the slope,
the lower the compliance (stiffer).
0
• N ormal curve: Compliance = ∆V/∆P = 800 mL/4 cm H2O = 200 mL/cm H2O
• A telectasis requires an extreme effort to open collapsed alveoli.
• C ompliance of lungs also ↑ with age.
∆V = 800
∆P = 4 Atelectasis (collapse)
4 8 12 16 20 24 28 32
Airway Pressure (cmH2O)
Clinical Correlation: Changes in Lung Compliance
↑ Compliance Emphysema • Less elastic recoil of lungs, so FRC ↑
• Chest wall expands and becomes barrel-shaped
• Also, ↑ RV, ↑ TLC, ↓ FVC, ↑ Raw
↓ Compliance* Fibrosis, respiratory • Tendency of lungs to collapse ↑, so FRC ↓
distress syndrome • Also, ↓↓ TLC, ↓ RV, ↓↓ FVC
Definition of abbreviation: Raw, airway resistance.
*Restrictive lung disease: a condition that reduces the ability to inflate the lungs (e.g., ↓ compliance).
278
►►Elastic Properties of the Lung and Chest Wall ORGAN SYSTEMS │3. The Respiratory System
100 At FRC the forces (see arrows)Chest Wall Emphysema The figure to the left shows the pressure−volume relationships of
Vital are in equilibrium the lung, the chest wall, and the lung and chest wall together.
Capacity FRC
Lung & ChEemstpWhyaslel,mNaFoirbmroasils • A t FRC, the system is at equilibrium and the airway pressure
% 80 = 0 cm H2O. At FRC, the elastic recoil of the lungs tends to
collapse the lungs. The tendency of the lungs to collapse is
60 balanced exactly by the tendency of the chest wall to spring
outward.
40
• The result of the opposing forces of the lungs and chest
wall cause the intrapleural pressure (Pip) to be negative (a
vacuum). The Pip is the pressure in the intrapleural space,
which lies between the lungs and chest wall.
Lung
20 Clinical Correlation
Fibrosis
0 If sufficient air is introduced into the intrapleural space, the Pip
becomes atmospheric (0 mm Hg), and the lungs and chest wall
follow their normal tendencies: the lungs collapse and the chest
_20 _10 0 +10 +20 +30 wall expands. This is a pneumothorax.
Airway Pressure (cmH2O)
►►Surface Tension • T he attractive forces between adjacent molecules of liquid are stronger than
those between liquid and gas, creating a collapsing pressure.
P T/r
Psmall > Plarge 2T
• Laplace’s Law: P = , where P = collapsing pressure
r T = surface tension
r = radius of alveoli
• Large alveoli (↑r) have low collapsing pressures (easy to keep open).
• S mall alveoli (↓r) have high collapsing pressures (difficult to keep open).
• Surfactant reduces surface tension (T). With ↓ surfactant (e.g., premature
infa�nts), smaller alveoli tend to collapse (atelectasis).
• Surfactant, produced by type II alveolar cells, ↑ compliance.
►►Airway Resistance
Airflow Q = ∆P where Q = airflow
R ∆P = pressure gradient
R = airway resistance
Airway R= 8hl where R = resistance
resistance p r4
η = viscosity of inspired gas
� l = airway length
Changes in r = airway radius
airwa�y Medium-sized bronchi are the major sites of airway resistance
(not the smaller airways because there are so many of them).
resistance
• Bronchial smooth muscle:
− Parasympathetic nervous system → bronchoconstriction via M3 muscarinic recep-
tors (↑ resistance)
− Sympathetic nervous system → bronchodilation via β2 receptors (↓ resistance)
• Lung volume:
↑ lung volume → ↓ resistance (greater radial traction on airways)
↓ lung volume → ↑ resistance
• Viscosity or density of inspired gas:
↑ density → ↑ resistance (deep sea diving)
↓ density → ↓ resistance (breathing helium)
279
ORGAN SYSTEMS │ 3. The Respiratory System ►►The Breathing Cycle
Inspiration Expiration At rest (FRC): Pa = Patm = 0 mm Hg
0.5 Inspiration
0.4 1. Inspiratory muscles contract.
0.3 2. Thoracic volume ↑.
3. Pip becomes more negative.
0.2 VT
0.1 Change in Lung Volume (l) FRC 4. Lungs expand (also causes Pip to be more negative because
of ↑ elastic recoil).
0
5. Pa becomes negative.
-5 Intrapleural Pressure
(cmH2O) 6. Air flows in down pressure gradient (Patm − Pa).
-6 Expiration
-7 1. Muscles relax.
2. Thoracic volume ↓.
-8 Flow (l/sec) 3. Pip is less negative.
+ 0.5 4. Lungs recoil inward (also causes Pip to be less negative).
5. Pa becomes positive.
0 6. Air flows out down pressure gradient (Pa − Patm).
Clinical Correlation
_ 0.5 Alveolar Pressure Obstructive lung disease: a condition that causes an abnormal
+1 (cmH2O) increase in Raw. Chronic obstructive pulmonary disease
(COPD) such as emphysema → destruction of elastic tissue → ↑
0 lung compliance → collapse of airways on expiration (dynamic
compression). This occurs in normal individuals during a forced
expiration but can occur during normal expiration in COPD. COPD
patients learn to expire slowly and with pursed lips.
_1 +30 _11
+38 +19
Definition of abbreviations: FRC, functional residual capacity; Pa, alveolar pressure; Patm, atmospheric pressure.
280
►►Pulmonary Disease Obstructive Disease Restrictive Disease ORGAN SYSTEMS │3. The Respiratory System
Normal
7 7 7
FEV1
6 6
6
5
FEV1 FVC
5
4
FVC
3
Lung Volume (liters) 5
Lung Volume (liters)
Lung Volume (liters)4 4
3 FEV1
3
FVC
2 2
2
1 1
1
0 0
0 1 second 1 second FVC FRC TLC RV
1 second
FEV1 = 80% (or 0.80) FEV1 FVC FRC TLC RV FEV1 = 88%
FVC FVC FVC
= 50%
• Forced vital capacity (FVC) is the TLC RV FRC FVC FEV1 FEV1/FVC Most
volume of air that can be expired with a ↓↓ ↓↓ Diagnostic
maximal effort after a maximal inspiration. Obstructive ↑ ↑↑ ↑↑ NC ↓
pattern or ↓ NC or ↑ ↓wiFthE↑V1T/FLVCC
• Forced expiratory volume 1 (FEV1) is ↓↓ ↓ ↓
the volume of gas expired during the first Restrictive ↓↓ ↓ FVC with
second. pattern ↓ TLC
Definition of abbreviation: NC, no change.
►►Summary of Classic Lung Diseases
Disease Pattern Characteristics
Asthma Obstructive Raw is ↑ and expiration is impaired. All measures of expiration are ↓ (FVC, FEV1, FEV1/FVC). Air
is trapped →↑ FRC.
COPD Obstructive • Combination of chronic bronchitis and emphysema
• There is ↑ compliance, and expiration is impaired. Air is trapped →↑ FRC.
− “Blue bloaters” (mainly bronchitis): impaired alveolar ventilation → severe hypoxemia with
cyanosis and ↑ Paco2. They are blue and edematous from right
heart failure.
− “Pink puffers” (mainly emphysema): alveolar ventilation is maintained, so they have
normal Paco2 and only mild hypoxemia. They have a reddish complexion and breathe
with pursed lips at an ↑ respiratory rate.
Fibrosis Restrictive • There is ↓ compliance, and inspiration is impaired.
• A ll lung volumes are decreased, but because FEV1 decreases less than FVC,
FEV1/FVC may be increased or normal.
281
ORGAN SYSTEMS │ 3. The Respiratory System Gas Exchange
►►Partial Pressures of O2 and CO2
Dalton’s Law of Partial Pressures: Partial pressure (pgas) = total pressure (Pt) × fractional gas concentration (Fgas)
Alveolar ventilation Alveolar gas =e q V•ucaot2io×nK: P/Paaoc2o=2P; (ioK2=− Pco2/R = 760 − 47 = 713)
equation: V• a Pb − Ph2o
. 160 mm Hg Ambient PO2 = F(Patm)
150 mm Hg PIO2 = F(Patm – 47)
Alveolar Ventilation (VA)
I = Inspired
PAO2 = 100 mm Hg
PACO2 = 40 mm Hg
End Capillary
PvO2 = 40 mm Hg PO2 = 100 mm Hg Systemic
PvCO2 = 45 mm Hg PCO.2 = 40 mm Hg Arterial
PaO2 = 95 mm Hg
Pulmonary Capillary Blood Flow (Qc) PaCO2 = 40 mm Hg
A = alveolar, a = systemic arterial
Equation O2 CO2
Dry inspired air (any Fgas 0.21 0
altitude)
Dry air at sea level Pgas = Fgas × Pb 0.21 (760) = 160 0
Pgas = Fgas × (Pb – Ph2o) 0.21 (760 − 47) = 150 0
Inspired, humidified COO2:2P: Va• oco2 2=KP/Rio2 − Paco2/R
tracheal air (Pio2) 150 – 40/0.8 = 100 (280 mL/min × 713)/5,000 mL/min = 40
Alveolar air (Pagas) —
100 40
Systemic arterial (completely equilibrates with (CO2 is from pulmonary capillaries and
blood (Pagas) alveolar O2 if no lung disease)
equilibrates with alveolar gas)
(MPiv-xceod2v) enous blood — 40
(O2 has diffused from arterial 45
(CO2 has diffused from tissues to venous
blood into tissues)
blood)
All pressures are expressed in mm Hg.
Definition of abbreviations: K, constant; Paco2, partial pressure of alveolar icnasrpbiorenddoioxxyigdeen; ;PVa• coo2,2,pCarOtia2 lpprroedsuscutrioeno; fRa,lvreesoplairraotoxryygeenxc; hPabn,ge
barometric pressure; Ph2o, water vapor pressure; Pio2, partial pressure of
ratio.
282
►►Diffusion • Vgas ∝ D(P1 – P2) × A/T ORGAN SYSTEMS │3. The Respiratory System
Fick’s Law of Diffusion where Vgas = diffusion of gas, D = diffusion coefficient of a specific gas, A =
surface area, T = thickness.
Time course in
pulmonary capillary • A and T are physical factors that change mainly in disease.
• D of CO2 >>> O2
Intense Normal Cardiac
Exercise Output
PO2 in blood (mmHg)100 Abnormal Alveolar • A red blood cell remains in capillary for
Normal Grossly Abnormal Venous 0.75 seconds (s)
50 • E quilibrium is reached in 0.25 s in normal
lung at resting state.
• Exercise reduces equilibration time,
but there is still enough reserve for full
equilibration of oxygen in a healthy
individual.
0 0.25 0.50 0.75
Time in capillary (sec)
Perfusion-Limited Gases Diffusion-Limited Gases
Gases that equilibrate between the alveolar gas and Gases that do not equilibrate between the alveolar gas and the
pulmonary capillaries are perfusion-limited. The amount of pulmonary capillaries are diffusion-limited. The amount of gas
gas transferred is not dependent on the properties of the transferred is dependent on the properties of the blood-gas barrier.
blood-gas barrier.
• O2:
• O2 (under normal conditions) − Blood-gas barrier is thickened in fibrosis.
• N2O (nitrous oxide) − Surface area is ↓ in emphysema.
• CO2 − I ntense exercise ↓ time for equilibration in pulmonary
capillaries (can occur in normal lungs).
− L ow O2 gas mixture (less partial pressure gradient, can
occur in normal lungs)
• CO: Binds so avidly to Hb, Paco does not ↑ much. Used to
measure the pulmonary diffusing capacity.
283
►►Oxygen Transport and the Hemoglobin−O2 Dissociation Curve
ORGAN SYSTEMS │ 3. The Respiratory System
Total O2 content at high pressure • Each hemoglobin (Hb) molecule has four subunits.
Hemoglobin saturation (%)100 includes dissolved O2 20
80 Temperature PCO2 16 O2 Content (ml/100ml) • Each subunit has a heme moiety with an iron in the ferrous
Hb-O2 H+ 2,3-DPG 12 state (Fe2+), and two α and two β polypeptide chains.
60 • O2 capacity: maximal amount of O2 that can bind to Hb
• O2 content*: Total O2 in blood (bound + dissolved)
= (O2 capacity × % saturation) + dissolved O2
40 8 = (1.39 × Hb × Sat ) + 0.003 PO2
100
20 4 • Content reflects O2 bound to Hb (the amount of O2 that is
dissolved is trivial compared to bound).
0 20 40 60 80 100 120 140 600 • Partial pressure reflects dissolved O2.
PO2 (mmHg)
Key Pressures Key Saturation % Shift to Right (↑ P50) Shift to Left (↓ P50)
Pao2 = 100 mm Hg Almost 100% saturated • Facilitates unloading • Facilitates loading
• ↑ temperature, ↑ Pco2, • ↓ temperature, ↓ Pco2,
Pv-o2 = 40 mm Hg 75% saturated
P50 = 27 mm Hg 50% saturated ↓ pH, ↑ 2,3-DPG ↑ pH, ↓ 2,3-DPG
• E xercising muscle is hot, • CO poisoning
acidic, and hypercarbic
Definition of abbreviations: Hb, hemoglobin concentration; Sat, saturation; P50, Po2 at 50% saturation.
*1.39 mL of O2 binds 1 g of Hb (some texts use 1.34 or 1.36).
►►Additional Changes in the Hemoglobin–O2 Dissociation Curve
Polycythemia
24 Arterial O2 Content (vol%) Normal
content CO
increase
20 Normal Hb = 15
16 Arterial 100%
O2 Content content sat.
decrease Anemia
(vol%) 12
38°C 100% PO2 in Blood
8 pH = 7.40 sat. (mm Hg)
100% CO poisoning is dangerous for three reasons:
sat.
1. CO left-shifts the curve (↓ P50), causing ↓ O2
4 unloading in tissues.
P50
2. C O has 240 times greater affinity for Hb as O2,
0 thus ↓ the O2 content of blood.
0 10 20 30 40 50 60 70 80 90 100 110 120 130 140
3. CO inhibits cytochrome oxidase
PO2 (mm Hg)
• Polycythemia and anemia change arterial O2 content.
• Pao2 and P50 remain the same.
284
►►CO2 Transport ORGAN SYSTEMS │3. The Respiratory System
CO2
CO2 Plasma Cl–
HCO3–
CO2 + H2O H2CO3 H+ + HCO3–
Carbonic
Anhydrase
Hb - CO2 Hb - H
Red Blood Cell
Forms of CO2
Percentages reflect contribution in arterial blood.
1. HCO3− = 90%
2. C arbamino compounds (combination of CO2 with proteins, especially Hb) = 5%
3. Dissolved CO2 = 5%
►►Pulmonary Blood Flow
Resistance (R) Very low
Compliance Very high
Pressures Very low compared with systemic circulation
Effect of Pao2 • Alveolar hypoxia → vasoconstriction.
• This is a local effect and the opposite of other organs, where hypoxia → vasodilation.
• This directs blood away from hypoxic alveoli to better ventilated areas
• This is also why fetal pulmonary vascular resistance is so high. Pulmonary resistance ↓ when the
first breath oxygenates the alveoli, causing pulmonary blood flow to rise.
Gravity Upright posture: greatest flow in base; lowest in apex
Filter Removes small clots from circulation
Vasoactive substances Converts angiotensin I → AII; inactivates bradykinin; removes prostaglandin E2 and F2α and
leukotrienes
285
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[libribook.com] MedEssentials for the USMLE Step 1 14th Edition
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