2. Cardiovascular Physiology
Dr. Abdulhalim Serafi, MB ChB,MSc,PhD,FESC
Assistant Professor & Consultant Cardiologist
Faculty of Medicine and Medical Sciences
Umm Al-Qura University
Makkah Al-Mukarramah
Saudi Arabia

3. CARDIAC OUTPUT (COP) Outline: Definition and formal value of:
- Cardiac output & cardiac index.
- End-systolic volume and end-diastolic volume
- Stroke volume and ejection fraction.
Physiological and Pathological variations in COP.
Factors effecting cardiac output:
- Changes in heart rate.
- Changes in stroke volume (venous return, myocardial
strength & ABP).
Further Reading:
Guyton: Textbook of Medical Physiology
Ganong: Review of Medical Physiology

4. CARDIAC OUTPUT
Cardiac Output: (CO or COP) is the amount of blood pumped by each ventricle per minute. It is also called minute volume.
In adults, COP is about 5-6 liters/ minute.
Cardiac output/one square meter of the body surface area is called cardiac index which is normally about 3.2 liters/ min/sq. meter.
Normally, the output of both ventricles is equal I.e the output of the right ventricle into the pulmonary circulation equals the output of the left ventricle into the systemic circulation.
CARDIAC OUTPUT is calculated as follows:
COP = Heart rate X Stroke volume.
Heart rate is the number of heart beats per minute;
normally it is about 70 beat/ minute.

5. Stroke volume is the volume of blood pumped by each ventricle per beat; normally it is about 70 ml/ beat.
END-SYSTOLIC VOLUME (ESV) & END_DIASTOLIC VOLUME (EDV):
During diastole of the ventricles, filling of the ventricles with blood normally increases the volume of each ventricle to about ml.
The volume of blood present in each ventricle at the end of ventricular diastole is called end-diastolic volume (EDV) and it is about ml.
During ventricular systole, as the ventricles empty, the volume decreases about ml.
The volume of blood ejection by each ventricle during each ventricular systole is called stroke volume (=70-80 ml).

6. At the end of ventricular systole, the remaining volume of blood in each ventricle is about ml.
The volume of blood present in each ventricle at the end of ventricular systole is called end-systolic volume (ESV) and it is about ml.
End-Diastolic Volume (EDV) End-Systolic Volume (ESV)
During muscular exercise:
Venous return to the heart is increased   EDV.
Force of ventricular contraction is increased   ESV.
 of EDV &  of ESV  marked  of SV (stroke volume)
The percentation of SV (stroke volume) to EDV (end-diastolic volume) is called ejection fraction (EF). Normally, it is about 65%.
During Muscular Exercise:
 EDV + of ESV    SV (2 or 3 times its normal value e.g. 200 ml/beat

7. Distribution of Cardiac Output (COP):
The COP of the right ventricle is distribute to the lungs.
The COP of the left ventricle is mainly distributed as follows:
Physiological and Pathological variations in COP:
Increase of COP
- Physiological causes:
Anxiety and excitement (50-100%).
Muscular exercise (up to 100%).
Eating (after meals 30%)
Exposure to hot weather.
Late pregnancy

8. - Pathological causes physiological causes:
Anemia.
Hyperthyroidism
Excessive secretion of adrenaline.
Decrease of COP:
- Sitting or standing after prolonged lying down in
recumbent position ( 20-30%).
Pathological Causes:
- Heart disease (heart failure, rapid arrhythmia,
myocardial infarction).
- Decreased blood volume (hemorrhage)
- Acute venous dilatation

9. COP Normal = 5 – 6L/min > COP < COP
Physiological Pathological Physiological Pathological
* Emotion or * Anemia * Change of * Heart disease:
excitement * Hyperthyroidism positive from Myocardial
(50-100%) * Fevers lying down infarction
* Exercise * Excessive (recumbent) Rapid
(up to secretion of position to; arrhythmias
or 100%) adrenaline * Sitting ( * Decreased
* Eating %) blood volume:
after meals * Standing Haemorrhage
50-40%) (20-30%) * Acute venous
* Exposure dilatation
to hot
weather
* Pregnancy
(100%)

10. MEASUREMENT of CARDIAC OUTPUT
Application of Fick’s principle: This method depends on determination of the O2 consumption/ minute and the O2 content in both the arterial and venous blood. The cardiac output = O2 consumption/ difference between the arterial and venous O2 content
Fick’s Principle: “The amount of a substance taken up by an organ per minute = arterial level of this substance minus its venous level x blood flow per minute”
If the organ is the lung O2
If the substance is O2
 O2 consumption = (Arterial O2 content – venous O2 content) x blood flow I the lungs (=COP of the right ventricle)

11. 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

12. Arterial O2 content – venous O2 Content
i.e.
Thus,
If O2 consumption/ minute = 250 ml/ min
Arterial O2 content = 190 ml/ 1000 ml blood
Venous O2 content = 140 ml/ 1000 ml blood
 COP =
250 x 1000 = 250 x 1000 = 5000 ml/ min=5 liters/ min
If consumption/ minute = 250 ml/ min, arterial O2 content
O2 19 ml/100 ml blood% venous=14 ml/ 100 ml blood
250 x 1000 = 250 x 100 = 5000 ml/ min=5 liters/ min
Cardiac output =
O2 Consumption/ minute
Arterial O2 content – venous O2 Content

13. The indicator dilution technique: This method depends on injecting a known amount of a radioactive isotope (or a dye) into the arm vein and its average concentration in the arterial blood and the time it takes during a single circulation through the heart are determined, then the CO is calculated as follows: if 5 mg of the indicator were injected, and its average concentration in the arterial blood was 1.6 mg/liter and the time of a single circulation through the heart was 39 seconds, then the output in this period = 1.6/5=3.1 liters, and the CO/ minute = 3.1 x 6039 = 4.7 liters.
Thermodilution Technique (in which cold saline is used as an indicator)
Echocardiography (unlike other methods, it is a non-invasive method).

14. CONTROL OF CARDIAC OUTPUT
FACTORS AFFECTING CARDIAC OUTPUT
Changes in COP may be due to:
Changes in heart rate (HR) or
Changes in the stroke volume (SV) or
Changes in both HR and SV as during muscular exercise.
Heart Rate: is controlled by the cardiac centers in the medulla oblongata and the autonomic nerves (sympathetic and parasympathetic) which supply the cardiac muscle, changes in heart rate may be due to:
Nervous Factors i.e. impulses from the different parts of the body which modify the activity of the cardiac centers.
Chemical Factors i.e. changes in the chemical composition of blood.
Physical Factors i.e. changes in the body or blood temperature.

15. Changes in COP may occur due to changes in HR or SV (or
Stroke Volume is controlled by:
Length of the cardiac muscle fibers which is not dependent on cardiac innervations. The force of contraction and consequently the amount of blood ejected (=SV) depends on:
- Preload i.e. the degree of stretch of the muscle fibers before contraction and this is affected by venous return.
- After-load i.e. resistance against which blood is ejected and this is affected by arterial BP.
Cardiac Nerves (sympathetic and parasympathetic) which may increase or decrease the force of contraction.
COP = HR X SV
Changes in COP may occur due to changes in HR or SV (or
both e.g. during muscular exercise).

16. Effect of heart rate on cardiac output:
Therefore, there are 4 factors that affect COP:
1. Heart rate
2. Venous return (preload)
3. Myocardial stretch (contractility)
4. ABP (after load)
COP = HR X SV
Effect of heart rate on cardiac output:
Moderate or physiological changes of the heart rate, exert almost no effect on COP. Provided that venous return remains constant, moderate changes in heart rate are compensated by opposite changes in the stroke volume, so the COP remains constant i.e.
 HR   SV (due to shortening of the diastolic period and this ventricular filling). Thus the increase in HR is compensated by  SV and the COP remains normal.

17. Excessive or pathological changes of the heart rate, will decrease COP provided that venous return: remains constant. Excessive increase of the heart rate (as in paroxysmal tachycardia) or excessive decrease of heart rate (as in complete heart block) will decrease COP because the changes in the SV will be insufficient to balance the changes in heart rate.
In muscular exercise, both HR and SV are increased because the venous return is increased, therefore the COP is increased.

18. Moderate changes (physiological changes) in heart rate with constant venous return  no effect on COP. This is because these changes are compensated by opposite changes in the stroke volume; so COP remains constant e.g.
Excessive changes (physiological changes) in heart rate with constant venous return   of COP. This is because these changes can not be compensated b sufficient changes in the stroke volume e.g.
Moderate  of HR (up to 100/min)
COP=HR X SV
 
=100 x 50
=5000
ml/m
(normal
COP)
Moderate  of HR (up to 100/min)
 
= 50 x 100
(normal COP)
Marked  of HR (up to 200/min as in paroxysmal take up)
COP=HR x SV
 
=200 x 20
=4000
ml/min
( COP)
Marked  of HR (30/min as in complete heart block)
 
=30 x 130
=3900

19. During muscular exercise venous return to the heart is   
HR &  SV marked  of COP:
 VR   EDV (up to 200 as 250 ml/min)
 EDV  stronger contraction of the ventricles (Starling’s Law)   ESV ( to 30 ml or even 10 ml)
 EDV +  ESV  marked  of SV (SV  2 or 3 times its normal value e.g.  SV to 200 ml)
 VR + many other factors  marked  of HR (HR  up to 140/min or more).
In heavy m. exercise COP is  up to L/min or even
more in well trained athletes (COP is  up to L/min).

20. Effect of venous return on COP:
The volume of blood pumped by each ventricle per minute (=COP) depends on the volume of blood returning to the heart per minute (=venous return). Normally, COP=VR.
Increased venous return, increases the EDV and the
preload of the ventricular muscle and according to
Starling’s Law, the force of contraction becomes stronger leading to an increase in both the SV and COP. Thus, the excess VR is pumped to prevent stagnation of blood in veins.

21. Factors affecting venous return to the heart:
Venous pressure gradient:
Normally, the pressure difference between the venous pressure at the start of venules and the right atrial pressure is more than enough to help return of venous blood from the tissues to the heart during recumbent position.
VR is directly proportional to the pressure gradient i.e  pressure gradient   venous return and VV.
Respiratory movements (thoracic pump):
The VR increases during inspiration due to increased negativity of the intra – thoracic pressure from – 3 to – 8 mmHg. Deep inspiration produces much increase in VR.
VR decreases during expiration and is markedly decreased during deep (forced) expiration.

22. Skeletal muscle contraction (muscle pump):
The squeezing effect of contracting muscles on veins during contraction helps VR. The valves present in the lumen of large veins prevent back of blood during muscle relaxation.
Skeletal muscles are peripheral pumps because by their repeated contraction and relaxation, they act as pumps which push the blood towards the heart.
Diameter of arterioles:
Vasodilatation of the arterioles increases while vasoconstriction of the arterioles decreases venous return to the heart.

23. Capillary tone:
Capillary tone refers to the number of closed capillaries at rest. Normally about 90% of the capillaries are closed and the blood passes in about 10% o the capillaries which are open.
If all capillaries are opened e.g. by histamine, this leads to accumulation of blood in capillaries leading to marked decrease of VR, COP and ABP (=histamine shock).
Vasomotor tone (diameter of veins:
Veins contain normally about 60% of the blood volume. Decrease of the venous tone  dilatation of veins  increased capacity of veins  decrease of VR and vice versa (vasoconstriction   VR).
Blood volume:
Venous return is directly proportional to blood volume i.e. decrease of blood volume as in haemorrhage  decrease of VR while increase of blood volume  increase of VR.

24. Gravity:
In the erect posture, gravity increases VR from parts above the level of the heart (head & neck) and decreases VR from parts below the level of the heart (lower limbs).
However, the effect of gravity on VR from the lower limbs is antagonized by:
Respiratory movements (thoracic pump).
Muscular activity (muscle pump).
Vasomotor tone.
Normally, venous return/minute (5 L/minute) = cardiac output (5 L/minute). Therefore, the volume of blood pumped by the heart/min depends on the volume of blood returning to the heart/min.
 VR   EDV   force of ventricular contraction (Starling’s Law)   COP.

25. FACTORS THAT DETERMINE THE PUMPING CAPACITY OF THE HEART
Under normal conditions, the pumping capacity of the heart
is determined by the following four factors:
THE END-DIASTOLIC VOLUME (Starling’s Law):
The pumping power of the heart is directly proportionate to the end-diastolic volume within limits.
THE SYMPATHETIC TONE TO THE HEART:
The sympathetic tone to the heart increases its pumping capacity. The resting sympathetic tine to the heart increases its pumping capacity of the heart down to 13 L/min. maximal sympathetic denervation decreases the pumping capacity of the heart down to 10 L/min. maximal sympathetic stimulation increases the pumping capacity up to 25 L/min.

26. HYPERTROPHY OF THE HEART:
When the heart is exposed to repeated or prolonged high work load, the heart hypertrophies. Physiological cardiac hypertrophy (e.g. as in athletes) increases the pumping capacity up to 35 L/min.
AORTIC IMPEDANCE:
Aortic impedance is the resistance which meets the blood as it flows from the left ventricle into the aorta. It is normally determined by the arterial blood pressure level.
Aortic impedance increases by an increase in the arterial blood pressure or by aortic valve stenosis.
The work capacity of the heart = (the pumping capacity) x (the aortic impedance). If the work capacity of the heart is constant, so any increase in the aortic impedance would decrease the pumping capacity of the heart.

27. FACTORS THAT DETERMINE THE VENOUS RETURN
The venous return is determined by three basic factors:
I- The mean systemic filling pressure (MSFP or PS): This is the pressure measured everywhere in the systemic circulation one minute after blood flow has been stopped by clamping the large blood vessels at the heart. Normally, it is about 7 mmHg. It is an indicator if the degree of filling of the systemic circulation. The MSFP is the driving force for the venous return. The venous return is directly proportionate to the MSFP level.
II- The right atrial pressure (RAP): This is the mean pressure in the right atrium. Normally, it is about 2 mmHg. It is also called the “central venous pressure”. The difference between the MSFP and the RAP is called the “pressure gradient for venous return”. Any increase in the RAP decreases the venous return. At RAP of 7 mmHg, with other factors constant, the venous return stops.

28. III-. The resistance to venous return (RVR): This is the
III- The resistance to venous return (RVR): This is the resistance which the blood meets during its flow from the arterial side up to the right atrium. This resistance occurs at the arterioles and veins.
The relationship between these factors and venous return is
expressed by the formula:
MSFP – RAP
RVR
where,
VR = Venous return
MSFP = Mean systemic filling pressure (PS)
(normal value = 7 mmHg)
RAP = Right atrial pressure. (Normal value=2 mmHg)
RVR = Resistance to venous return.
(normal value = 1 mmHg/L/min)
VR =

29. EFFECT OF ABP (after-load) on COP
Arterial BP represents on after-load to the ventricular muscle i.e. resistance against which blood is ejected into the arteries.
If ABP is increased, the resistance to blood flow in increased  decrease of SV (for several beats)  temporary decrease of COP.
However, blood accumulation in the left ventricle increases the EDV, and according to Starling’s Law, the force if ventricular contraction increases, thus the SV will increase and the normal level of COP will be restored.
N.B:
Pumping of normal COP against high ABP   LV work
LV dilation if hypertension is not treated  LV failure.

30. (contractility) ON COP
 ABP LV work   resistance to blood blow from the left ventricle into the aorta   SV (for several beats)  temporary  COP.
However, the accumulated blood in LV   EDV   myocardial contraction   SV &  COP to normal.
EFFECT OF MYOCARDIAL STRENGTH
(contractility) ON COP
The force of contraction of the ventricular muscle affects the stroke volume and consequently the cardiac output. COP is directly proportional to the strength of the myocardium which depends mainly on:
Initial length of the ventricular muscle during diastole (EDV):
The COP is directly proportional to the initial length of the ventricular muscle during diastole “Starling’s Law”, thus increased EDV  increase of ventricular contraction  SV & COP. The EDV depends mainly on VR.

31. O2 is supplied to the myocardium through the coronary arteries
O2 is supplied to the myocardium through the coronary arteries. If coronary blood flow decreases, this leads to  O2 supply to the myocardium (hypoxia)   myocardial strength   COP.
Coronary thrombosis  myocardial infarction  heart failure   COP.
Positive inotropic factors e.g.:
Sympathetic stimulation,   contractility   SV &  COP.
Catecholamine   contractility   SV &  COP.
Digitalis (drug)   contractility   SV &  COP.
 ischemia of the cardiac muscle   O2 supply (hypoxia   myocardial strength   COP.
Coronary thrombosis in big branch of the coronary arteries  myocardial infarction  heart failure and death may occur.