| | Venous Return| Their Regulation & Failure

Color index 434 Team Physiology [email protected] us: contact

Explained in: - Important Only in Only in - Further Additions Boys’ Slides Girls’ Slides -Guyton Ch.9, P.110 & Ch.20 - In boys’ slides -Linda’s Ch.4, P.151 Story Time..

You may think the titles of these lectures are confusing! Indeed they are a BIT confusing but when you understand the relation between those titles everything will make perfect sense! Let me tell you a story: Cardiac output (CO) is the volume of pumped by the heart

per minute and one of the most important factors determining CO Slide is left ventricular end diastolic volume (EDV) which depends on Venous Atrial è è venous return (VR), which also determines (AP). Return Pressure Thus, it follows that there is not only a relationship between CO and EDV but also a relationship between CO and AP. CO and VR each can be examined separately as a function of right AP.

Simply EDV VR depends mainly on è right AP which will determines è EDV which will determines è CO

Where is the stroke volume in all this? Stroke volume is the amount of blood pumped per beat! While CO is amount of blood pumped per minute! But READ it for a better understanding... abetter itfor READ But Additional

We will come to know the details of each one of them and the Cardiac ç ç factors that regulates it.. output Don’t you worry, just set back read and enjoy the journey..J Definitions: ² Cardiac Output (CO) [mL/min] : Amount of blood pumped by each per minute. = (5L/min) ² Stroke Volume (SV) [mL/beat]: Volume of blood is ejected by each ventricle per beat. = (70mL/beat) ² End-diastolic volume (EDV) [mL]: Amount of blood remaining in the heart by the end of . =(140mL) ² End-systolic volume (ESV) [mL]: Amount of blood remaining in the heart by the end of . = (70mL) ² (EJ) [%]: The percentage of blood that is pumped out of a filled ventricle as a result of a heartbeat.

ü CO = SV x HR |UNIT : ml/beat x beat/min = ml/min ü SV = EDV - ESV ü EJ = SV / EDV ü = CO / BSA1|UNIT is litres per minute per square metre L/min/m2 Cardiac Index This allows direct comparison Is a haemodynamic parameter that relates the cardiac of the cardiac index of large output(CO)from left ventricle in one minute to body and small patients surface area (BSA),thus relating heart performance to 1: Body surface area the size of the individual. Cardiac Output Cardiac output is the blood flow generated by each ventricle per minute (i.e., the blood pumped by each ventricle per minute).

² The cardiac output is equal; to the volume of blood pumped by one ventricle per beat (stroke volume) times the number of beats per minute () CO = SV x HR ü CO is well regulated according to tissue metabolic demands.

ü Accordingly, if the metabolic rate is increased, the CO and VR are increased to maintain optimal O2 supply to the active tissues.

² The cardiac output at rest is approximately 5 L/min. ² The body’s averages 5 to 5.5 liters. ² Thus, each ventricle pumps the equivalent of the entire blood volume each minute. ² During , the CO can increase to 20 to 25 liters/min and to as high as 40 liters/min in well trained athletes. ² The difference between the resting CO and the maximum volume of blood the heart is capable of pumping per minute is known as the cardiac reserve CO = SV x HR Stroke Volume = EDV - ESV Heart Rate (Beats/min) Recall! Stroke volume is Volume of blood is ejected by each ventricle per beat. (mL/beat) é INCREASE ê DECREASE Due to

The heart’s ability to contract. Due to *Stimulation *Electrical abnormality *Excitation by activity, The force of contraction. *Some medications drugs, medications... The volume of blood available to be pumped. Increase éCO Decrease êCO (venous return). Affected by changes in Excessively Fast!!éé Too slow!!êê . Not have enough time êCO decreased Resistance within the . to adequately fill with significantly. blood between beats. Severe hemorrhage. Innervations required: Shock. Decrease êCO

Other Implanted pacemakers.

Variables Heart damage. ² To increase the Cardiac output: Extreme infection. ü Increase Stroke volume Any factor effects the stroke volume will affect cardiac output as well. ü Increase Heart rate up to a limit ü Increase both like in exercise Ejection fraction: = SV / EDV The percentage of blood that is pumped out of a filled ventricle as a result of a heartbeat. ü The heart does not eject all the blood in the ventricle. ü Only about ⅔ of the blood is normally pumped out with each beat. ü That fraction is referred to as the Ejection Fraction. it’s decrease when the becomes diseased...

Variations of Cardiac output Physiological Variations Pathological Variations Increases CO é

Exercise (700%) Fever

Eating (30%) Hyperthyroidism

High Environmental Temperature Anaemia

Pregnancy Decreases CO ê

Anxiety (50-100%) Hypothermia

Sympathomimetics ‘Epinephrine’ Myocardial Diseases eg. Infarction, failure..etc

Decreases CO ê Rapid Arrhythmias

Sitting Or Standing From Laying Position (20-30%) Hypothyroidism Arrow toward center = Decreases Arrow away from center = Increases Exercise Pregnancy

Eating Anxiety

High Sympathomimetics Temperature

Variations of Cardiac Output

Hyperthyroidism Sitting or standing Hypothyroidism form laying position

Myocardial Fever & diseases Hypothermia

Rapid arrhythmias Anaemia Factors Affecting Cardiac Output CO = Stroke Volume x Heart Rate

An increase or decrease in heart rate will affect the cardiac out put as said previously

Stroke volume with all the factors affecting it (mentioned previously) will affect CO But most important factors are:

Preload Contractility Afterload = = Venous Return Arterial Venous Return (Preload) It represent the amount of blood returning to the heart per minute [Ventricular filling] ² Relationship between Cardiac output & Venous Return Because the cardiovascular system is a closed loop. If they’re not equal è blood accumulate in either: the systemic or pulmonary circulation.

² Its controlled by many factors:

Thoracic pump Frank-starling’s ü é Atrial Contractility ü ü mechanism ü é ü é Ventricular Compliance Muscle pump Gravity ü ü ü é By: - é Blood Volume - ê Venous Compliance ü Blood volume ü Tissue metabolism ü ê Heart Rate

Valsalva maneuver Mean systemic ü ü pressure Will Increase the é Preload Factors Affecting Venous Return (Preload)

-Sympathetic fibers supply veins Mean (sympathetic vasoconstrictor tone) -This is important to maintain venous pressure and hence Systemic creates pressure gradient (from high to low )to push blood Filling to the right atrium. Pressure - Acute venous dilatation can lead to significant drop in VR and so cardiac output.

Skeletal -When the skeletal muscle compress the veins, they force Muscle the blood to the heart. Pump -Valves in the veins prevent backflow of blood .

-The amount of blood push upward decreased and VR decreased. Gravity -CO decreased and that decreased tissue in brain then that will cause unconsciousness.

Factors Affecting Venous Return (Preload)

-Affect blood flow to the heart. During Inspiration: Thoracic pressure become more(-) Thoracic Pressure inside the abdomen is (+) that push blood through the vessels from abdomen to the Pump thoraxes . During Expiration : The thoracic pressure here is (+) Pressure inside the abdomen is(-)

-It is a forced expiration against closed glottis. (Straining) Valsalva -Increase intrathoracic positivity. Maneuvear -Significant compression of the veins.

-Ability of the heart to change it force of contraction and therefore stroke volume in response to changes in venous return. Frank- -Ability of the heart to pump all blood coming to it, without allowing Lo starling’s systemic stasis within limits. -Good filling of the Heart with blood (VR) è Cardiac stretch è Law of the éCardiac contractionè éCO heart -The greater stretch of the myocardial fibers ,the stronger the force of the .مثل الطاط .contraction *قدرة القلب على التكيف مع كمية الدم القادم اليه Mechanism of Starling’s Law REMEMBER: • Increase In preload -Sarcomere: . Between 2 Z lines & its the unit of contraction • Increase in sarcomere length . -Troponin c: The part of troponin where • Increase troponin C calcium sensitivity calcium bind. . -Cross bridge: attachment of the actin & myosin • Increase rate of cross-bridge attachment and . detachment • Amount of tension developed by the muscle . fibers (force of contraction)

Increase the stroke volume The troponin and myosin have to be at optimum (التشابك المثل) interdigitation

The maximum Drop of force of the cardiac stretch leads to contractility & stroke volume. stronger contraction

force of contraction contraction of force Over stretch that leads to loss of (preload) interdiction & can lead to muscle tear End Diastolic Volume (EDV) Recall! EDV is the amount of blood remaining in the heart by the end of diastole =(140mL)

Factors Affecting Increase EDV é Stronger Atrial Contractioné Increased Total Blood Volumeé Increased Venous Toneé The tone that is present in the whole of the veins as a result of The sympathetic discharge that EDV comes to it from the . Increased Skeletal Muscle Pumpé

Increased -ve Intrathoracic Pressureé

Decrease EDV ê Standing The end diastolic volume (affected by the Increased Intrapericardial Pressureé same factor that control the venous return (Previously discussed) Decreased ventricular compliance ê Afterload Can be defined as the (load) that the heart must eject blood against ü The afterload is closely related to the aortic pressure.

• When Arterial pressure is reduced ê .

• The Ventricle can eject blood more rapidly é .

• Increases the Stroke volume é .

• Decreases the End-systolic volume ê . ESV What is The Effect of an Increase in Afterload on Stroke Volume ?

• When afterload increases .

• An increase in End-systolic volume é .

• Decrease in Stroke volume ê .

• Shifts the frank-starling curve down and to the right StrokeVolume (mL) . (from A to B)

Explanation: an increase in afterload decreases the velocity of fibre shortening, This reduces the rate of LVEDP1 (mmHg) volume ejection so that more blood is left within the 1: Left ventricular end diastolic pressure ventricle at the end of systole (increase end-systolic volume) A decrease in afterload shifts the Frank-Starling curve up and to the left (A to C).

Factors Affecting Afterload ü Vascular tone (and therefore blood pressure) ü Aortic stiffness ü Myocardial tension (affected by hypoxia, ) ü Preload ü Valvular regurgitation Afterload is increased when.. ü Aortic stenosis ü Arterial hypertension Extrinsic Regulation of Cardiac output :

² Chemicals ² Nervous: ü Potassium ü Sympathatic ü Catecholamines ü Parasympathatic ü Calcium ü Thyroxin If in a controlled experimental model right atrial pressure1 is varied .التغير (independent variable) and the cardiac output measured .التغير التابع (dependent variable)

Enhanced

10 Normal ü You will find that as RAP is increasing è the CO increases. ü When the PRA2 is about 0 mmHg (note that PRA normally fluctuates Depressed with atrial contraction and respiration), the cardiac output in an 5 adult human is about 5 L/min.

of theانحدار Because of the steepness ² cardiac function curve, very small changes in PRA (just a few mmHg) (preload) can lead to large changes in CO 0 10

1: Venous Return (Preload) èRight atrial pressure èEDV 2: PRA = Pressure of Right Atrial

Volume. Volume. New Way New Which when when Which

dimensions, thus multiplied by the Record Real-Time Record computing Stroke Stroke computing ²

heart rate, gives CO. rate, heart changes in ventricular inventricular changes ²

Example

)

/ml blood /ml

2 ) . /min 2 Heart rate will be given then just multiply the HR by the CO justmultiplybythe HR the 0.15 mLO mlO . ) & ( 0.15 ) /min

. 2 - are expressed as : are expressed 0.2 mL 2 ven ml

2 L/ min L/

O 0.2

5 - 250 ml O ?

/ ( ( / is analyzingexpiredair blood sample from each Ven. & Art. from each Ven. sample blood or 2 CO art

2 /min 2 O content are ( ( ml/min / ven : Mixed venous Mixedvenous :

mlO

2 2 : Body Oxygen consumption. consumption. Body Oxygen : /mL blood blood /mL

/ min/ 2 250 ven

VO

2 5000 2 art : Arterial Oxygen contents. contents. Oxygen Arterial : art

OldWay 2 2 expressed as:

art & O measured by measured 2

measured by measured O O VO

2

Ventricular Stroke Volume : CO / HR/ CO : Volume Stroke Ventricular

Frick Principle Frick mlO

CO= CO= CO= How much will be How much will

VO mL O mL

The blood content of O The blood content

respectively, and VO

if O

²

²

² Measurement of Cardiac Output Output Cardiac of Measurement Pressure Atrial Atrial

Venous Return (Preload) è è EDV EDV 1 min 1 Cardiac Output

ç ç ç ç çç ç Stroke Volume Afterload Afterload

Simple illustration (Congestive Heart Failure) The inability of the heart to pump adequate output for the body metabolism needs ² Manifested mainly by: ü Inadequate cardiac output ü Build-up of blood in veins behind left heart or right heart (increased venous pressure)

Acute Heart Failure Chronic Heart Failure

Development Rapid Long-term

Duration Hours/Days Months/Years

1-Cardiopulmonary Bypass Surgery. 2-Acute infection (Sepsis). -The most common cause of CHF is a heart attack which causes damage to the muscles of Causes 3-Acute Myocardial infarction. left ventricle. 4-Severe Arrhythmias.

Associated with the heart undergoing Does it undergo life threatening because the heart does not Adaptive Responses (E.g. Dilation, Adaptive have time to undergo compensatory Hypertrophy), however it can be Response? adaptations. deleterious. Myocardial Pericarditis Infarction

Idiopathic Thyroid disease cardiomyopathy

Coronary artery Arrhythmias disease

Causes of Heart Failure

Septic Shock Myocarditis

Chronic Hypertension Valve disease

Bacterial Viral Cardiomyopathy Cardiomyopathy Overall Mechanism Route of Heart Failure

In response to these changes the body Causes of the will immediately reduced renal release output of urine (Compensatory during cardiac mechanisms) that failure. will activate the Sympathetic and RAS1 systems.

1: Renal Artery Stenosis RAS System Effect on Heart Failure

Reduced blood flow to the kidneys causes marked increase in renin secretion. this in turn increases the formation of II.

In the chronic stage of heart failure, large quantities of aldosterone are secreted by the adrenal cortex. Which results by the effect of angiotensin. This elevation of aldosterone level increases the reabsorption of sodium and water from the renal tubules. Additional The significance of Natriuretic Peptides

They are a family of peptides that share a common ring structure.

ANP1: is a released by the atrial walls of the heart when they become stretched It increases in the blood by 5- to 10-fold in severe heart failure. ü It has a direct effect on the kidneys to increase greatly their excretion of salt and water. ü ANP plays a natural role to help prevent (BNP) extreme congestive symptoms during cardiac failure.

(ANP) BNP2: Present in high concentrations in cardiac tissues, particularly the ventricles.

ü An elevated BNP level is a marker of increased LV filling pressure and LV dysfunction

Types of Heart Failure

Left-Sided HF Right-Sided HF Increase Aortic pressure causes backward Increase Right Ventricle pressure causes pressure travels to Left Ventricle èThen backward pressure on Right Atria è Increasing Pulmonary Veins èFinally goes to the lung right atrial pressure è Pathogenesis èSort of accumulation of the blood in the lung Stagnation of the blood On the: that can not go back to the heart, Causing ü Superior Vena Cava è Increased Jugular Pulmonary Edema present as area of venous pressure consolation on the X-ray imgings. ü Inferior Vena Cava èAscites1

² Respiratory manifestations: ü Tachypnea: increased work of breathing ² Symptoms: ü Crackle sound: it is a sign of development of ü Ascites (backward pressure of Inferior Signs, pulmonary edema, heard initially in the lung vena cava on the hepatic circulations) Symptoms bases, however if severe it can be heard ü Increased throughout the lung fields. (backward pressure of Superior vena & ü Cyanosis: which suggests severe hypoxemia, is a late sign of severe pulmonary edema. cava on the hepatic circulations) (manifestations) ² Cardiac manifestations: ü Hepatomegaly (backward pressure of ü Lateral displacement of apex beat (Which occurs Inferior vena cava on the hepatic in the case of cardiomegaly –enlargement) circulations) ü : (additional ) may be ü Pitting peripheral edema heard as a marker of increased blood flow, or increased intra-cardiac pressure.

1: An accumulation of fluid in the peritoneal cavity. (Abdomen) Types of Heart Failure (Signs & Symptoms) Signs & Symptoms Left-Sided HF Right-Sided HF

Pitting Edema Mild to moderate Moderate to sever (legs and hands)

Pulmonary edema (fluid in lungs) Abdomen (Ascites) Fluid Retention Pleural effusion (fluid around lungs)

Organ Heart Liver (Mild jaundice may be present) Enlargement

Mild to moderate raised in jugular venous Severe raised in jugular venous vein pressure Neck Veins vein pressure (JVP) (JVP), Neck veins visibly distended

Shortness of Prominent dyspnea Dyspnea present but not as prominent breath Paroxysmal nocturnal dyspnea (PND) Comparison Loss of apatite Bloating (any abnormal general swelling) Present but not as prominent Gastrointestinal Constipation Symptoms are more prominent Left-Sided HF Right-Sided HF

Pulmonary Edema Dyspnea As area of consolation Elevated JVP Ascites Pitting Edema Physiological adaptation to Heart Failure (compensation mechanisms)

² Reduction of cardiac workload, including both preload and afterload. ü Increased sympathetic stimulation: * * éHR * éBP ² Enhancement of . ü Increased sympathetic stimulation: *éForce of contraction

² Control of excessive retention of salt and water. ü Greater blood volume → peripheral and pulmonary edema Starling Curve in Heart Failure

Complications of Progressive HF ² Prolonged sympathetic activation to the heart ² Hypertrophied heart ² Excessive salt and water retention: ² Over-distended ventricle MCQs 1- In normal conditions Venous return (preload) must be: A. Equal to cardiac output B. Less than cardiac output C. Greater than cardiac output

2- Excessive increase in heart rate: A. Increase cardiac output B. Decrease cardiac output

3- Which one of the following causes an increase in stroke volume? A. Increase preload B. Decrease preload C. Gravity

4- 44 years old women came to the ER having a Heart Failure and her physical examination reveals pitting peripheral edema, ascites, and hepatomegaly. Which mostly type of Heart failure is she having ? A. Left-sided heart failure 1.A B. Right-sided heart failure 2.B 3.A 4.B Done by: ² Najoud Alrasheed ² Rana Alhumeamydi ² Najd Alomran ² Naijlaa2020 ² Amal Alaseeri ² Sarah Aljasser ² Hadeel Alsulmi ² Nourah Almofarej ² Nouf Almasoud ² Mada Albatli ² Nouf Alharbi