CARDIOVASCULAR PHYSIOLOGY

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CARDIOVASCULAR PHYSIOLOGY
STUDENT MANUAL Dr. Guido E. Santacana
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CARDIOVASCULAR PHYSIOLOGYLECTURES

• STUDENT LECTURE NOTEBOOK
• Guido E. Santacana Ph.D.
• DEPT. of PHYSIOLOGY

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INTRODUCTION TO CARDIOVASCULAR PHYSIOLOGY

• GENERAL ASPECTS OF THE CARDIOVASCULAR SYSTEM

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MAIN FUNCTIONS OF THE CIRCULATORY SYSTEM

• Transport and distribute essential substances to
  the tissues.
• Remove metabolic byproducts.
• Adjustment of oxygen and nutrient supply in
  different physiologic states.
• Regulation of body temperature.
• Humoral communication.

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THE MAIN CIRCUIT
COLLECTING
PUMP
TUBULES
DISTRIBUTING
THIN VESSELS
TUBULES
6
Pressure Profile of the Circulatory System
7
Distribution of Blood in the Circulatory System
8
Organization in the Circulatory System
SERIES AND PARALLEL CIRCUITS
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CARDIAC ELECTROPHYSIOLOGY

• LECTURE NOTEBOOK
• Guido E. Santacana Ph.D.

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GENESIS OF THE MEMBRANE POTENTIAL AND EQUATIONS
TO REMEMBER!!
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THE RESTING MEMBRANE POTENTIAL OF THE CARDIAC CELL
If membrane permeable only to K
If membrane permeable To both Na and K
If membrane permeable To Na, K plus with A
Na/K Pump
12
WHY NOT Na 0R Ca FOR THE CARDIAC CELL MEMBRANE
POTENTIAL ?
13
ACTION POTENTIALS FROM DIFFERENT AREAS OF THE
HEART
ATRIUM
VENTRICLE
SA NODE
time
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ELECTROPHYSIOLOGY OF THE FAST RESPONSE FIBER
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PHASE 0 OF THE FAST FIBER ACTION POTENTIAL
Chemical Gradient
Electrical Gradient
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K CURRENTS AND REPOLARIZATION

• PHASE 1-TRANSIENT OUTWARD CURRENT (TOC) Ito
• PHASE 1-3-DELAYED RECTIFIER CURRENT IK
• PHASE 1-4-INWARDLY RECTIFIED CURRENT IKl

17
THE PLATEAU PHASE AND CALCIUM IONS
OPEN
CLINICAL VALUE
L Ca CHANNELS
Ca BLOCKERS
10MV
T Ca CHANNELS
-20MV
NO (physiological)
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EFFECTS OF Ca CHANNEL BLOCKERS AND THE CARDIAC
CELL ACTION POTENTIAL
DILTIAZEM
ACTION POTENTIAL
CONTROL
10 uMol/L 30 uMol/L
10
30
CONTROL
10
FORCE
30
TIME
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Clinical CorrelationEarly After-Depolarizations
Torsades de Pointes
0mV
-60mV
-90mV
Early After-Depolarization
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OVERVIEW OF SPECIFIC EVENTS IN THE VENTRICULAR
CELL ACTION POTENTIAL
21
Overview of Important Channels in Cardiac
Electrophysiology
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More Channels!
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ELECTROPHYSIOLOGY OF THE SLOW RESPONSE FIBER
0
2
0
mvs
-40
3
4
ERP
RRP
-80
time (msec)
RECALL INWARD Ca CURRENT CAUSES DEPOLARIZATION
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CONDUCTION OF THE ACTION POTENTIAL IN CARDIAC
FIBERS
LOCAL CURRENTS
-
-
-
-
-
-
-
-







-
-
-
-
-
-
-
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FIBER A
FIBER B
DEPOLARIZED ZONE
POLARIZED ZONE
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CONDUCTION OF THE ACTION POTENTIAL

• FAST RESPONSE Depends on Amplitude,Rate of
  Change,level of Em.
• SLOW RESPONSE Slower conduction.More apt to
  conduction blocks.
• WHAT ABOUT MYOCARDIAL INFARCTS AND CONDUCTION?

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EFFECTS OF HIGH K ON CONDUCTION AND AP OF FAST
FIBERS
0MV
AP-AMP
Em
K3mM
K7mM
K14mM
0MV
K16mM
K3mM
WHAT HAS VARIED? LOOK AT Em,AP SLOPE-AMPLITUDE
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HIGH K AND m/h Na GATES
LOWER Em
HIGH K
CLOSED h GATES (SOME)
LOWER AP AMPLITUDE
LOWER Na ENTRY
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EXCITABILITY OF FAST AND SLOW FIBERS
FAST
m/h GATES COMPLETE RESET AFTER PHASE 3
CONSTANT AND COMPLETE RESPONSE IN PHASE 4
SLOW
LONG RELATIVE REFRACTORY PERIOD.
POST-REPOLARIZATION REFRACTORINESS
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AFTER THE EFFECTIVE OR ABSOLUTE REFRACTORY PERIOD
(FAST FIBER)
0
MV
ARP
-80
RRP
TIME
30
POST-REPOLARIZATION REFRACTORINESS (SLOW FIBER)
200 MSEC
C
0
B
MV
A
-60
POSTREPO
TIME
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RHYTMICITY
AUTOMATICITY
SA NODE
AV NODE
ectopic foci
IDIOVENTRICULAR- PACEMAKERS
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THE SA NODE PACEMAKER POTENTIAL
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CHARACTERISTICS OF THE PACEMAKER POTENTIAL
RECALL PHASE 4-PACEMAKER POTENTIAL(PP) OBSERVED
HERE. FREQUENCY DEPENDS ON
THRESHOLD,RESTING POTENTIALS

AND SLOPE OF THE PP
34
CAUSES OF THE PACEMAKER POTENTIAL
K
OUT
if
iCa
IN
iK
Na
Ca
35
THE PACEMAKER POTENTIAL CURRENTS AFTER
DEPOLARIZATION
iCa
if
iK
WHICH CURRENT WILL BE MORE AFFECTED BY ADRENERGIC
STIMULATION? WHICH BY CHOLINERGIC STIMULATION?
36
LOOKING AT THE PACEMAKER CURRENTS
voltage
iK
if
ionic currents
iCa
37
EFFECTS OF Ca CHANNEL BLOCKERS ON THE PACEMAKER
POTENTIAL
NIFEDIPINE
CONTROL
(5.6 X 10-7 M)
0
MV
-60
TIME
38
OVERDRIVE SUPRESSION AND AUTOMATICITY OF
PACEMAKER CELLS

• Na/K ATPase ENHANCEMENT BY HIGH FREQUENCY.
• CONSEQUENT HYPERPOLARIZATION.
• SUPRESSION OF AUTOMATICITY.
• RECOVERY TIME REQUIRED.
• ECTOPIC FOCI/SICK SINUS SYNDROME.

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THE CONDUCTION SYSTEM OF THE HEART
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ATRIAL AND ATRIOVENTRICULAR CONDUCTION
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NODAL DELAY
REGION OF DELAY
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UNI AND BIDIRECTIONAL BLOCKCLINICAL IMPLICATIONS
B
A
ANTEGRADE BLOCK
NORMAL
D
C
REENTRY UNIDIRECTIONAL BLOCK
BI
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Clinical CorrelationRe-entry TachycardiasParoxys
mal Supraventricular Tachycardia
Ischemic Tissue
Fast Pathway
Slow Pathway
Fast Pathway
Slow Pathway
Normal Conduction
Re-Entry Circuit
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AV NODE AND AV BLOCKS
FOCUS ON N REGION
ECG
NORMAL
1ST DEGREE
PROLONGUED AV CONDUCTION TIME
2ND DEGREE
1/2 ATRIAL IMPULSES CONDUCTED TO VENTRICLES
3RD DEGREE
VAGAL MEDIATION IN N REGION/COMPLETE BLOCK
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CONDUCTION IN THE VENTRICLES

• PURKINJE FIBERS WITH LONG REFRACTORY PERIODS.
• PROTECTION AGAINST PREMATURE ATRIAL
  DEPOLARIZATIONS AT SLOW HEART RATES.
• AV NODE PROTECS AT HIGH HEART RATES.

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QUICK QUIZ
Which of the following is not true about the
effect of acetylcholine (Ach) in the
electrophysiology of the cardiac pacemaker
cell A. Ach lowers the magnitude of the minimum
repolarization potential. B. Ach lowers the slope
of the pacemaker potential. C. Ach decreases the
SA node frequency. D.Ach increases the ik current
of the pacemaker cell. E. Ach decreases the iCa
current of the pacemaker cell. The main reason
why the AV node filters out high stimulation
frequencies from the SA node is A. The long
pathway that the stimulus must traverse in the AV
node. B. Post Repolarization Refractoriness of AV
nodal cells. C. The AV nodal cell is always
hyperpolarized D. Ca is the main ion in Phase 0
of the AV nodal cell. E. I need to review this
section very fast.
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CARDIAC MECHANICS

• MAIN THEMES
• THE HEART AS A PUMP
• THE CARDIAC CYCLE
• CARDIAC OUTPUT

CHAPTER 3 BL
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LENGHT/ TENSION AND THE FRANK-STARLING RELATION
LEFT VENTRICULAR PRESSURE
INITIAL MYOCARDIAL FIBER LENGHT LEFT VENTRICULAR
END-DIASTOLIC VOLUME
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PRELOAD AND AFTERLOAD IN THE HEART

• INCREASE IN FILLING PRESSUREINCREASED PRELOAD
• PRELOAD REFERS TO END DIASTOLIC VOLUME.
• AFTERLOAD IS THE AORTIC PRESSURE DURING THE
  EJECTION PERIOD/AORTIC VALVE OPENING.
• LAPLACESS LAW WALL STRESS, WS P X R / 2(wall
  thickness)

50
LEFT VENTRICULAR PRESSURE AND AFTERLOAD AT
CONSTANT PRELOADS
EFFECT OF INCREASED PRELOAD
LEFT VENTRICULAR PRESSURE
PEAK ISOMETRIC FORCE
AFTERLOAD (aortic pressure)
NOTE WHAT HAPPENS IN THE NORMAL HEART VS ONE IN
THE LAST PHASES OF CARDIAC FAILURE?
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CONTRACTILITYTHE VENTRICULAR FUNCTION CURVE
EFFECT?
CHANGES IN CONTRACTILITY
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dP/dt AS A VALUABLE INDEX OF CONTRACTILITY
MAX dP/dt
B
120
A
C
LEFT VENTRICULAR PRESSURE (mmHg)
40
.6
TIME (s)
.2
53
CARDIAC CYCLE
Rapid Ventricular Filling
Reduced Ejection
Atrial Systole
Rapid Ejection
Isovolumic Relax.
Reduced Ventricular Filling
Atrial Systole
Isovolumic contract.
Aortic opens
Aortic closes
Mitral opens
Mitral Closes
S1
S2
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QUICK QUIZHow to find out that you know the
Cardiac Cycle.
150
Atrial systole
Mitral closes
Aortic opens
LEFT VENTRICULAR VOLUME (ML)
Aortic closes
Mitral opens
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TIME (SEC)
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Clinical CorrelationDiagnosis of Aortic Stenosis
by Pressure Graphs
Aortic Stenosis
Normal
Aorta
Aorta
Ventricle
Ventricle
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LEFT VENTRICULAR PRESSURE/VOLUME P/V LOOP
END OF SYSTOLE
120
F
E
D
80
LEFT VENTRICULAR PRESSURE (mmHg)
40
END OF DIASTOLE
B
A
C
0
100
150
50
LEFT VENTRICULAR VOLUME (ml)
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EFFECT OF PRELOAD ON THE VENTRICULAR P/V LOOP
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EFFECT OF AFTERLOAD IN THE LEFT VENTRICULAR P/V
LOOP
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EFFECT OF CONTRACTILITY ON THE LV P/V LOOP
ESPVR 2
ESPVR 1
LEFT VENTRICULAR PRESSURE (mmHg)
1
2
VOLUME (ml)
60
QUICK QUIZ
PRELOAD
AFTERLOAD
CONTRACTILITY
61
CARDIAC OUTPUT AND THE FICK PRINCIPLE
BODY O2 CONSUMPTION
Lungs
250mlO2/min
PULMONARY ARTERY
PULMONARY VEIN
PaO2
PvO2
0.15mlO2/ml blood
0.20mlO2/ml blood
Pulmonary capillaries
O2 CONSUMPTION (ml/min)
CARDIAC OUTPUT
-
PvO2
PaO2
62
HEMODYNAMICS

• VELOCITY,FLOW,PRESSURE
• LAMINAR FLOW
• POISEUILLES LAW
• RESISTANCE(SERIES-PARALLEL)
• TURBULENT FLOW AND REYNOLDS NUMBER

CHAPTER 5 BL
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REQUIRED CONCEPTS
VELOCITY DISTANCE / TIME V
D / T
FLOW VOLUME / TIME Q VL
/ T
VELOCITY -FLOW- AREA V Q / A
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CROSS SECTIONAL AREA AND VELOCITY
A 2cm2 10cm2 1cm2
Q10ml/s
a
b
c
V 5cm/s 1cm/s 10cm/s
V Q / A
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HYDROSTATIC PRESSURE
100
136cm
0
200
100
0
200
P p x g x h
0
100mmHg
100
136cm
0
200
P Pressure mmHg p density g gravity h
height
100
0
200
0
66
ENERGY OF A STATIC VS A DYNAMIC FLUID
TOTAL ENERGY POTENTIAL E. KINETIC E.
TE PE
KE
FLUID AT REST (HYDROSTATIC )
FLUID IN MOTION (HYDROSTATIC

HYDRODYNAMIC)
67
VELOCITY AND PRESSURE
100
0
200
0
68
POISEUILLES LAW GOVERNING FLUID FLOW(Q) THROUGH
CYLINDRIC TUBES
(Pi - Po) r
4
(FLOW)Q
8nL
DIFFERENCE IN PRESSURE
RADIUS
VISCOSITY
LENGHT
69
RESISTANCE TO FLOW IN THE CARDIOVASCULAR SYSTEM
BASIC CONCEPTS
Rt R1 R2 R3. SERIES RESISTANCE 1/Rt
1/R1 1/R2 1/R3 PARALLEL RES.
R1
PARALLEL
SERIES
R2
R1
R2
R3
R3
WHAT REALLY HAPPENS IN THE CVS?
LOWER R
LOWER R
HIGHER R
CAPILLARIES
ARTERY
ARTERIOLES
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LAMINAR VS TURBULENT FLOWTHE REYNOLDS NUMBER
LAMINAR FLOW
TURBULENT FLOW
p density D diameter v velocity n
viscosity
Nr pDv / n
laminar 2000 or less
71
QUICK QUIZZ
1. Which of the following vessels will produce a
dramatic decrease in blood flow through the
tissues by a change in radius? A. Aorta B.
Venules C. Arterioles D. Capillaries 3. After a
bout with hemorrhagic Dengue you would expect to
find a heart murmur at a lower level than before
the disease. A. True B. False
72
PV Loop Refresher
What happens from A to B?
73
ARTERIAL SYSTEM

• COMPLIANCE
• MEAN ARTERIAL PRESSURE
• PULSE PRESSURE
• PRESSURE MEASUREMENT

CHAPTER 26 BL
74
THE CONCEPT OF THE HYDRAULIC FILTER
SYSTOLE
DIASTOLE
COMPLIANT
RIGID
75
EFFECTS OF PUMPING THROUGH A RIGID VS A COMPLIANT
DUCT
0.1
PLASTIC TUBING
O2 CONSUMPTION (mlO2/100g/beat)
NATIVE AORTA
0
5
15
STROKE VOLUME (ml)
76
STATIC P-V RELATIONSHIP IN THE AORTA
INCREASE IN VOLUME
PRESSURE (mmHg)
77
ELASTIC MODULUS OR ELASTANCE
Ep ELASTIC MODULUS Da MAX. CHANGE IN
AORTIC DIAMETER. Db MEAN AORTIC DIAM.
Ep P / Da/Db
ELASTANCE COMPLIANCE
P
V
P
V
EP IS INVERSELY PROPORTIONAL TO C
78
MEAN ARTERIAL PRESSURE (MAP)
REMEMBER OHMS LAW?
CARDIAC OUTPUT
PERIPHERAL RESISTANCE
INSTANTANEOUS INCREASE
STEADY STATE INCREASE
79
EFFECT OF COMPLIANCE ON MAP
Qh- inflow (CO) Qr- outflow Ca- Compliance Pa- MAP
Pa Qh - Qr / Ca
SMALL Ca
ARTERIAL PRESSURE (mmHg)
LARGE Ca
INCREASE CARDIAC OUTPUT
TIME
80
PULSE PRESSURE
STROKE VOLUME
COMPLIANCE
V4
VB
V3
VOLUME
V2
VA
V1
P1
PA
P2
P3
PB
P4
PRESSURE
81
PULSE PRESSURE EFFECTS OF
TOTAL PERIPHERAL RESISTANCE
COMPLIANCE
TPR
B
A
82
CHAPTER 9 BL
COUPLING OF THE HEART AND BLOOD VESSELS
VASCULAR FUNCTION CURVE
HOW CARDIAC OUTPUT REGULATES CENTRAL VENOUS
PRESSURE
CARDIAC FUNCTION CURVE
HOW CENTRAL VENOUS PRESSURE (PRELOAD) REGULATES
CARDIAC OUTPUT
83
VASCULAR FUNCTION CURVE
HOW CHANGES IN CARDIAC OUTPUT INDUCE CHANGES IN
CENTRAL VENOUS PRESSURE?
8
Pmc
VASCULAR FUNCTION CURVE
B
CENTRAL VENOUR PRESSURE (mmHg)
A
-1
0
8
CARDIAC OUTPUT (L/min)
84
HOW BLOOD VOLUME AND VENOMOTOR TONE CHANGE THE
VASCULAR FUNCTION CURVE?
VASCULAR FUNCTION CURVE
8
TRANSFUSION
CENTRAL VENOUR PRESSURE (mmHg)
NORMAL
HEMORRHAGE
-1
0
8
CARDIAC OUTPUT (L/min)
85
TOTAL PERIPHERAL RESISTANCE AND THE VASCULAR
FUNCTION CURVE.
8
VASCULAR FUNCTION CURVE
CENTRAL VENOUR PRESSURE (mmHg)
VASODILATION
VASOCONSTRICTION
NORMAL
-1
0
8
CARDIAC OUTPUT (L/min)
86
THE CARDIAC FUNCTION CURVE
CARDIAC OUTPUT (L/min)
CENTRAL VENOUS PRESSURE (mmHg)
87
EFFECTS OF SYMPATHETIC STIMULATION ON THE CARDIAC
FUNCTION CURVE
CARDIAC OUTPUT (L/min)
CENTRAL VENOUS PRESSURE (mmHg)
88
HOW BLOOD VOLUME AND PERIPHERAL RESISTANCE CHANGE
THE CARDIAC FUNCTION CURVE?
VOLUME
RESISTANCE
CARDIAC OUTPUT (L/min)
CENTRAL VENOUS PRESSURE (mmHg)
89
THE CARDIAC FUNCTION CURVE IN HEART FAILURE
CARDIAC OUTPUT (L/min)
CENTRAL VENOUS PRESSURE (mmHg)
90
HEART - BLOOD VESSELSCOUPLING
91
CARDIAC ARREST!INMEDIATE EFFECT
FLOW STOPS HERE
PUMP
ARTERIES
VEINS
Qh
0L/min
Pa
FLOW CONTINUES HRE TRANSFER ART--gtVEINS
CPV2mmHgPv
Qr
5L/min
Qr CONTINUES AS LONG AS A PRESSURE GRADIENT IS
SUSTAINED
R 20mmHg/L/min
Qr Pa - Pv/20
92
CARDIAC ARRESTSTEADY STATE
FLOW STOPPED
PUMP
ARTERIES
VEINS
Qh
0L/min
Pa 7mmHg
Pv 7mmHg MEAN CIRCULATORY PRESSURE OR Pmc
95mmHg
FLOW STOPPED
5mmHg
Qr
0L/min
Qr 0 ( NO Pa - Pv DIFFERENCE)
93
WE START PUMPING!INMEDIATE EFFECT
FLOW STARTS
SOME VENOUS BLOOD
PUMP
ARTERIES
VEINS
Qh
1L/min
Pa 7mmHg
Pv 7mmHg
NO FLOW HERE YET
Qr
0L/min
94
FLOW RETURNS AT Qr AT THE NEW Qh
95
THE END