Cardiac Output and Regulation of Blood Pressure

Cardiac output is important for regulating blood pressure. What is cardiac output?

The volume of blood flowing through either the systemic or pulmonary circuit

Anything that decreases cardiac output also decreases?

Blood pressure

Anything that increases cardiac output also increases?

Blood pressure

Anything that affects heart rate or stroke volume affects _____ _____ and thus, blood pressure?

cardiac output

How is cardiac output calculated?

Calculated by multiplying heart rate by stroke volume

• Cardiac output (CO) = Heart rate (HR) x Stroke Volume (SV)

What is the normal adult cardiac output at rest?

5 L/min

What are three factors that govern stroke volume?

Preload, Contractility, and Afterload

What is preload?

The amount of pressure in the left ventricle immediately before the heart contracts - this pressure is determined by the amount of blood in the left ventricle just before systole

• volume of the blood in the ventricles right before the heart contracts, also called end-diastolic volume

• pressure in the left ventricle at the end of diastole. the immediate moment just before systole begins

What is contractility?

The force with which the heart contracts

• Contraction for a GIVEN preload

Increased preload results in increased or decreased SV?

Increased SV

Increased contractility results in increased or decreased SV?

Increased SV

What is afterload?

The pressure downstream of the heart and the aorta and on into the body (the force or load against which the heart pumps)

• The resistance to ejection during systole and the load that the muscle must move during the contraction

If you increase afterload, what happens to SV?

SV decreases. This is because the heart must work against a higher pressure, so the volume of blood that’s leaving the heart for a given preload and given force of contraction will be less

What is the difference between preload and afterload?

Preload is the stretch of the heart ventricles at the end of filling (diastole), while afterload is the pressure the heart must push against to eject blood into the body

What is preload determined by?

• Amount of venous return to the ventricle at the end of systole (end-systolic volume)

  • increased venous return would mean increased pressure in the ventricle which would yield increased preload, which means you’ll have increased stroke volume and therefore increased CO

• Blood in the left ventricle AFTER systole

  • Also known as end-systolic volume

  • The larger the volume of blood in the ventricle just before systole, the greater the pressure in the ventricle, leading to greater CO

Preload is estimated by measuring:

Measuring the central venous pressure for the right side of the heart and the wedge pressure of the left side of the heart

• Normal values:

  • 1-5mmHg for the right side

  • 4-12mmHg for the left side

When there is an increase in preload above normal limits, it reduces the force of the ventricular contraction and the ability of the heart to contract properly. What does this cause?

Causes decline in stroke volume and also increases ventricular end diastolic pressure. This causes pressures to increase or back up into pulmonary or systemic venous circulation, increasing plasma outflow and causing fluid to accumulate in lung tissues or peripheral tissues, leading to pulmonary edema or peripheral edema

What is the Frank-Starling law of the heart?

It describes the relationship of the heart stretch and the force of contraction

• Ventricles eject as much blood volume as they receive, and the more the ventricles are stretched (representing an increase in preload) the greater the force of the contraction

• Stroke volume is proportional to the end diastolic volume

• The law is valid as long as ventricular end-diastolic pressure stays in normal physiologic range (1-5mmHg in right ventricle and 4-12mmHg in left ventricle)

Examine the Frank-Starling relationship among end-diastolic volume/preload, myocardial stretch, force of contraction, stroke volume, and cardiac output.

Increased venous return increases the volume of blood in the resting ventricle, stretching the myocardial sarcomeres. Within normal physiological limits, greater resting stretch produces a proportionately stronger force of contraction during the next systole, increasing stroke volume and cardiac output.

What happens when preload exceeds the physiologic range?

Further muscle stretching causes a decline in cardiac output

• When preload exceeds this upper limit, excessive sarcomere stretching causes actin and myosin filaments to partially disengage. This impairs contractility, causing a decline in stroke volume and cardiac output, elevating ventricular end-diastolic pressure (VEDP), and causing fluid to back up into the pulmonary or systemic circulation (leading to pulmonary or peripheral edema).

The greater the preload the greater the _____ force

contraction

What are other factors aside from preload that increase contractility (positive inotropes)?

• Hypercalcemia - extra calcium in the blood is going to diffuse into the cardiomyocytes and produce a strong prolonged contraction

  • this is good up to a point, but as the distance between the ventricular depolarization and ventricular repolarization becomes more prolonged, there’s an increased risk for serious dysrhythmia

• Catecholamines

• Digitalis (this is a medicine)

• Excess thyroid hormone

• Dobutamine (this is a medicine)

What are some factors that decrease contractility (negative inotropes)?

• Hyperkalemia

  • if severe enough, can result in decreased contractility to the point that it can actually cause the heart to stop

    • membrane may become less excitable bc of inactivation of sodium channels and impaired function of the sodium-potassium pump. This reduced excitablity can result in slower impulse conduction, often observed as a widening QRS complex on EKG. If untreated, this can lead to cardiac arrest, as the heart can no longer repolarize effectively

  • as potassium levels exceed a certain level, the absolute resting membrane potential decreases or becomes less negative. This can lead to characteristic changes on an EKG including peak T waves, as hyperkalemia worsens

• Hypocalcemia

• Hypoxia

• Alcohol

• Beta blockers - intended to reduce contractility and lower BP

  • the reduced contractility improves the heart’s efficiency

What pressure is a good index of afrterload for the left ventricle?

Aortic systolic pressure

In individuals with hypertension, increased systemic vascular resistance means that the afterload is chronically what?

elevated

What happens if we have decreased afterload?

The heart is able to contract more rapidly and efficiently and move more blood

What happens if we have increased afterload?

Heart contractions will be slower and the workload will increase

Activity of what node is the primary determinant of heart rate?

Sinoatrial (SA) node

What is the average HR of healthy adults compared to resting HR in athletes?

• HR in average adult is 70bpm

• Resting HR in well-conditioned athletes is 50-60 bpm

• Resting HR in elite athletes can be as low as 50 bpm

Control of the HR includes activities of the:

• Central nervous system

• Autonomic nervous system

• Natural reflexes

• Atrial receptors

• Hormones

What is heart rate variability (HRV)?

The ability of the heart to change its rate and a measure of cardiac autonomic function

• adequate amounts of HRV in response to physiologic conditions is believed to be an important indicator of health

Ex: HR varies with respiration

What is the normal alteration in heart rate related to respiration called?

Sinus arrhythmia - caused by changes that occur with the chest cavity because of respiration

What pathophysiologic factors are linked to decreased HRV?

• Neurologic diseases

• Cardiovascular diseases

• Psychological distress

• Lack of effective coping mechanisms

• Mental health disorders

Where is the cardiovascular vasomotor control center (CVS) located?

Located in the medulla and pons

• Additional areas:

  • hypothalamus - regulates cardiovascular responses to changes in temp

  • cerebral cortex - adjust cardiac reaction to emotional states

  • thalamus - regulates HR and blood pressure

CVS and autonomic nervous system influence the ___ node rate

SA

• At rest, the HR in healthy individuals is primarily under the control of parasympathetic stimulation

  • Administration of drugs that block parasympathetic functions, such as anticholinergics, or physical interruption to the vagus nerve, cause tachycardia because this inhibitory parasympathetic influence is lost

Another factor that affects HR are the neural reflexes, specifically the baroreceptors. What are the two baroreceptors located?

One is in the carotid arteries and the other other is in the aortic arch

What does the output from the baroreceptor reflexes influence?

Influences the short-term regulation of the vessel diameter of arteries, the myocardial contractility, and the HR

• all three of these are components of blood pressure control

What do the baroreceptors do if blood pressure is too low (sympathetic response)?

• Increase the HR

• Increase myocardial contractility

• Increase systemic vascular resistance and cause vasoconstriction

What do the baroreceptors do if blood pressure is too high (parasympathetic response)?

The arteries will vasodilate and we will see decreased myocardial contractility and HR

• Pathway is glossopharyngeal nerve through vagus nerve to medulla CV to control center

Neural receptors that influence HR are also present in both atria.These are called atrial volume receptors. Where are they located?

They are located where the superior and inferior vena cava enter the right atria and where the pulmonary veins enter the left atria

The atrial volume receptors are stimulated when there’s too much plasma volume in the atria, and this stimulation increases what?

Urine volume

• In addition, atrial natriuretic peptides are going to be released from the atrial tissue in response to the increased blood volume. These peptides have diuretic or water excretion properties and natriuretic or salt excretion properties. The excretion of both water and salt is going to result in a decreased blood volume and pressure. Overall effect is that afterload is going to decrease and this is allows the heart to contract more rapidly and efficiently

What are the three layers of a blood vessel?

• Tunica intima

  • most inner layer that contains the endothelium and basement membrane

• Tunica media

  • middle layer that contains all the smooth muscle that allows the vessels to vasodilate and vasoconstrict

• Tunica externa

  • the external layer. contains nerves and lymphatic vessels

Blood vessel walls vary in thickness depending on the role of the vessel and the absence of one or more layers. What is an example of this?

Example of this is that the only layer that is present in the capillary is the endothelium

What are some important roles of the endothelium?

• Substance transport

• Coagulation, thrombus prevention , and fibrinolysis

• Immune system function

• Tissue and vessel growth

• Wound healing

The goal of anyone who is managing diabetes or hypertension is protecting the endothelium

What are arteries?

Thick-walled vessels that transport blood away from the heart

Arterial walls are made up of what kind of tissue?

• Connective tissue

• Fibrous connective tissue

• Smooth muscle

What are the two types of arteries?

Elastic arteries and muscular arteries

What are characteristics of elastic arteries?

They have a thick tunica media with more elastic fibers than smooth muscle fibers

• They are located close to the heart

• Elasticity allows the vessels to absorb energy and stretch as the blood is ejected from the heart during systole, and then during diastole, the elasticity promotes recoil of the arteries, which will help to maintain blood pressure within the vessels

What are characteristics of muscular arteries?

They make up medium and small arteries and are further from the heart than the elastic arteries

• They contain more muscle fibers and fewer elastic fibers than the elastic arteries

• They function to distribute blood to arterioles throughout the body. This plays a role in blood flow control and directing how diff body parts get blood flow

  • Ex: if running during exercise, more blood will be sent to the skeletal muscles

What is the capillary network composed of?

Connective channels called metarterioles and true capillaries

• metarterioles have smooth muscle cells in their tunica media

• true capillaries have no smooth muscle cells

  • There’s a ring of smooth muscle called a pre-capillary sphincter at the point where the capillary branches from the metarterioles

    • as these sphincters contract/relax, they are going to regulate blood flow through the capillary beds

    • The pre-capillary sphincters help to maintain the arterial pressure and regulate selective flow to vascular beds

A person’s heart rate is reduced. What is happening physiologically?

Stimulation of the parasympathetic nervous system

Compared to arteries, what are some characteristics of veins?

They are thin-walled, have fibrous connective tissue, and have a larger diameter

• some veins have valves that facilitate one-way flow of blood towards the heart

What is the skeletal muscle pump in the veins?

When the legs compress the deep veins, which assists the flow of blood toward the heart and against the force of gravity

The goal of having adequate blood pressure is to supply the oxygen and nutrients to the cells and the body. To make sure that happens, blood pressure determined by what three factors?

Cardiac output, blood volume, and peripheral resistance

There are a lot of inputs to peripheral resistance, and one of the concepts within that is the importance of arterial elasticity. What should elasticity in healthy arteries look like?

Should be good expansion and recoil that maintains steady blood flow throughout the cardiac cycle, which smooths out pressure fluctuation and decreases stress on small arteries

Why does BP rise with age?

Arteries become less distensible or less elastic

Blood pressure regulates blood flow to the body. What are three factors that affect blood flow?

Blood viscosity, vessel length, and vessel radius

How does thick blood viscosity impact blood flow?

Thick fluids move more slowly and cause greater resistance to flow than thin fluids

• This means the heart has to increase its cardiac output to maintain the same flow

Ex: when a person is dehydrated and water is lost from the blood, their blood is said to be more viscous. The red blood cells, white blood cells, and proteins like albumin are more densely packed. This causes greater resistance as the blood flows through the bloodstream

How does vessel length impact blood flow?

The longer the vessel, the greater the pressure and flow are going to decline

• A shorter length vessel is going to produce less resistance while a longer vessel is going to produce more resistance

How does vessel radius impact blood flow?

It has a very powerful influence over blood flow and is the most adjustable variable in what affects blood flow

• It controls resistance, and therefore, blood pressure

• Blood flow is proportional to the fourth power of radius

  • arterioles with a radius of 3mm the blood flow is 81 mL/sec. if the arteriole vasoconstricts to 1mm, the flow drops by a factor of 4

From the aorta to the capillaries, does blood flow increase or decrease?

Blood flow decreases. It decreases because:

• Greater distance traveled, more friction to decrease flow

• Greater cross-sectional area

• Farther from the heart, greater the total cross-sectional area

From the capillaries to vena cava, does blood flow increase or decrease?

Blood flow increases

• Large amount of blood forced into smaller channels

• Never regains velocity of large arteries due to friction losses along the vessel walls

What is laminar flow?

Occurs when concentric layers of molecules move “straight ahead”

• Flow is smooth and orderly with parallel fluid layers

• Flow increases at you get more towards the center of the vessel

What is turbulent flow?

Occurs where flow is obstructed, the vessel turns, or blood flows over rough surfaces, producing a murmur

• Flow is perpendicular or oblique to vessel

What are two mechanisms of venous return?

The thoracic pump (respiratory pump) and the skeletal muscle pump

How does the thoracic pump (respiratory pump) assist in venous return?

As we inhale there’s abdominal veins that can be compressed by expansion of the diaphragm. As those are compressed, that’s going to decrease that cross-sectional area and increase blood flow. These veins also contain valves that prevent venous flow from flowing backward as we exhale

• Increased negative pressure in the right atrium and right ventricle

• Increased abdominal pressure moves blood toward the heart

Which cardiac chambers have the thinnest wall and why?

The right and left atria; they are low-pressure chambers that serve as storage units and conduits for blood

Blood pressure is determined by what?

Cardiac output and peripheral vascular resistance

What are baroreceptors?

Specialized sensory nerve endings that act as stretch receptors, monitoring changes in blood pressure by detecting the tension in the walls of blood vessels and the heart

When stretch occurs, the baroreceptors are activated, which results in lowered or elevated blood pressure?

Lowered blood pressure

What are chemoreceptors?

They are specialized sensory cells that detect specific chemicals in the body or environment and convert them into electrical signals

• located in the medulla, aortic arch, and coronary arteries

• sensitive to oxygen, CO2, and hydrogen ions

What are important functions of chemoreceptors?

• Important for respiratory control

• Also important for transmitting impulses to the medullary cardiovascular center, which helps to regulate blood pressure

  • BP increases with hypoxemia (decrease in oxygen)

  • BP increases with hypercapnia (increase in CO2)

  • BP increases with lowered pH (acidosis)

How do hormones influence blood pressure regulation and blood flow?

• Influence blood pressure regulation through their effects on vascular smooth muscle and blood volume

• By constricting or dilating arterioles and organs, hormones can increases or decrease the blood flow in response to the body’s needs. They can redistribute blood volume during hemorrhage or shock and can also regulate heat loss

What are some key vasoconstrictor hormones?

• Angiotensin 2, which is part of the renin angiotensin-aldosterone system (RAAS)

• Epinephrine

• Norepinephrine

What are some key vasodilator hormones?

• Atrial natriuretic peptides

• Nitric oxide

• Adrenomedullin

• Endothelins

What are some hormones that affect blood pressure by regulating blood volume?

• Aldosterone

• Vasopressin

• Natriuretic peptides

By causing fluid retention or loss, aldosterone, natriuretic peptides, and vasopressin (ADH or antidiuretic hormone) can influence stroke volume and therefore blood pressure

When is the Renin-Angiotensin-Aldosterone System (RAAS) activated?

When there’s reduced blood flow to the kidney, and then renin as a result is going to be released into circulation. Renin is going to convert angiotensinogen into angiotensin 1, and then angiotensin 1 is going to be converted into angiotensin 2 by the ACE (angiotensin converting enzymes) found in the lungs

• This is where you’ll se the ACE inhibitors are potent blood pressure medications bc of the inhibition that they don’t allow angiotensin 1 to be converted into angiotensin 2

• Angiotensin 2 is a potent vasoconstrictor and will cause blood pressure to rise. As blood pressure rises, there will be increased flow to the kidneys

• Angiotensin 2 also causes release of aldosterone from adrenal cortex, and aldosterone causes the renal tubules to increase reabsorption of sodium and water into the blood. This increases blood volume → increases blood pressure

• Aldosterone also activates the thirst center, and this increase in extracellular volume is going to increase blood pressure

What are the vasodilating hormones?

• Nitric oxide - a soluble gas produced in the endothelial cells

  • Provide several protective functions related to normal endothelial function and vascular homeostasis, including:

    • regulation of vascular dilator tone

    • regulation of local cell growth

    • protects vessel from injury caused by platelets and other cells

• Adrenomedullin

  • Released by endothelial cells when there is vascular wall stress

  • plays a role in controlling vascular tone and blood pressure

• Endothelins

  • Produced in vascular smooth muscle, endothelium, and some organs

  • can act as vasodilators or vasoconstrictors

Which finding will cause the resistance in blood vessels to increase?

Increased blood viscosity

What are some determinants of coronary blood flow?

Coronary perfusion pressure, coronary bed vascular resistance, and anatomic factors

• It is directly proportional to coronary perfusion pressure and inversely proportional to vascular resistance of the coronary bed

What is coronary perfusion pressure?

That difference between pressure in the aorta and pressure in the coronary vessels

What anatomic factors influence coronary blood flwo?

The aortic valve cusps locations can obstruct coronary blood flow by occluding the openings of the coronary arteries during systole

• also during systole, the coronary arteries are compressed by ventricular contraction. During the period of systolic compression when blood flow is slowed or stopped, myoglobin provides the supply of oxygen to the myocardium

What are the two methods of regulating coronary blood flow?

Autoregulation and autonomic regulation

How does auto regulation regulate coronary blood flow?

Regulates blood flow by altering coronary arteriole diameter and by ensuring constant coronary blood flow

How does autonomic regulation regulate coronary blood flow?

Involves the sympathetic nervous system

Why is the lymphatic system important?

Important for maintaining fluid balance and immune system function, and transporting proteins, hormones, and liquids

• manages fluid balance by returning excess fluid to venous circulation

• Lymphatic fluid is made up primarily of water and small amounts of dissolved proteins, mostly albumin

• Lymph carries antigen-presenting cells and lymphocytes

• Valves allow one-way flow

There are two major lymphatic systems. What are they?

The right lymphatic duct and the thoracic duct

• the right lymphatic duct is going to drain the lymph from the right arm, the right side of the head, and the right upper thorax back to the right subclavian vein

• the thoracic duct drains lymph from the rest of the body and deposits it into the left subclavian vein

What is the most common cause of death in persons older than 65 years of age and the most common cause of morbidity?

Cardiovascular disease

• commonly seen with coronary artery disease and cerebrovascular disease (stroke)

What are some physiologic changes with age that affect the cardiovascular system?

• Blood vessel stiffening (blood vessel is less elastic and less distensible) and myocardial stiffening

  • these two changes lead to isolated systolic hypertension, which can increase the risk for MIs and stroke

• Changes in neurogenic control over vascular tone

  • evident when an older person goes from lying to sitting or sitting to standing. may see orthostatic hypotension as a result - sudden drop in BP is a result of baroreceptors in the carotid sinus and aortic arch not working properly. Their activity may decrease with age

• Increased occurrence of atrial fibrillation

• Loss of exercise capacity — leads to issues with venous return

• Left ventricular hypertrophy and fibrosis