Introduction to Human Physiology - 4 Cardiovascular System

Source: My personal notes from Introduction to Human Physiology | Coursera

Keep the Pressure Down

From Heart and Stroke Foundation session June 8, 2015 on how to manage blood pressure which is a symptom of future diseases.

High blood pressure = damage to arteries and weaker heart in the long term. Damage to arteries and reduced blood flow may result in damage to organs in the long term.

• DASH diet, similar to Canada food guide
• Normal blood pressure is 120/80 - systolic / diastolic
• Use vinegar, herbs, lemon juice, spices, fruit, etc. for taste in food.

Module Introduction

This module considers the circulatory system and its role in delivering oxygen and nutrients to the specific organs. We start with a discussion of the electrical and mechanical functions of the heart which enable it to generate a pressure gradient. This pressure gradient propels the blood through a closed series of blood vessels, in a unidirectional manner. In our discussion of the vasculature, we consider its role in the delivery of gases, solutes, and nutrients and in particular what factors govern their delivery at the tissue level. In the last lesson we consider the entire reflex loop (brain, heart, and blood vessels), its control, and its response to daily demands (rest and exercise) and how pathology affects these responses.

From <https://www.coursera.org/learn/physiology/outline>

Heart Electrical Activity

Conduction System / Structure of Heart

• 2 pumps in series (right = RT and left = LT)

• Blood moves for right to left

• Atria = top of heart chambers

• Ventricles = bottom of heart chambers

• Atria and ventricles are divided from each other. RT and LT are separated.

• Connective tissue between atria and ventricles isolate electrical activity of top from bottom.

• Electrical activity occurs in atria before ventricles.

• Pacemakers (SA, AV nodes) fires

  • AV node is gateway of electrical activity from upper chambers to lower chambers
  • Bundle of His (pronounced hiss) and purkinje fires activating ventricles.

Pacemaker Action Potential

• Pacemaker = unstable resting potential, slow action potential
• Remember contractile myocites were 220 msec. (they are considered faster than pacemakers)
• Slow action potential change
• “funny” Na+ channels are opening and closing at low voltages.
• mV = millivolts, move from -55mV to -35mV threshold.

Phase 4: K+ efflux (outflow) stopped, Na+ and Ca++ influx

Phase 0: Ca++ influx

Phase 3: K+ efflux

Heart Rate (HR) Control

• Sympathetic nervous system (SNS) speeds up closing of K+ channels, speeding up Phase 4 = less time to reach threshold
• Tachycardia > 100 beats per minute (bpm); tachycardia is required for exercise like running.
• Parasympathetic nervous system (PNS) increases K+ efflux (phase 3). Hyperpolarization which increasing time to reach threshold (e.g. much more negative mV starting for phase 4 and phase 4 takes longer).
• Bradycardia < 60 bpm
• Bradycardia can be achieved in certain states like sleeping.
• Athletes have low basal heart rates and have more parasympathetic tone and may have hearts rates classified as bradycardia (e.g. Lance Armstrong ~ 35 bpm).
• In pathology, low heart rates may indicate problems with the heart such has weakness or conduction issues.

Electrical Activity of the Whole Heart

• Electrodes can pickup electrical activity of the entire heart. They can pick up depolarization of the entire atria or ventricles.

• Activity:

  • SA node fires = atria depolarize
  • Delay at AV node, AV node fires
  • AV transfers to His bundle and Purkinje fibers = septum and ventricles depolarize
  • Heart wall depolarizes from inside to outside.
  • Repolarization in opposite direction

Electrocardiogram (ECG)

We can’t see individual depolarization activity of nodes; however, we can see summation of activity to all atria and ventricle cells. Summation is called the ECG.

P > QRS > T

P > Q and S > T have isoelectric intervals (electrical activity is fairly static)

QRS is related to the propagation of the cardiac impulse between the AV node and the Purkinje fibers

Which segments change in running/hard exercise?

• ST segment should shorten (rapid repolarization)
• R to R will shorten (more beats per minute)
• P-R segment shortens (rapid atrial depolarization).
• What about QRS? Turns out QRS changes are slight and not detectable.

Cardiac Rhythm & ECG

• Sinus rhythm = rhythm by SA node. Results in P - QRS - T

• Ectopic foci - rogue cells generating pacemaker functions

  • Pathology: Ectopic foci could result in heart disease conditions like not enough blood filling ventricles, irregular rhythms, fibrillation and may be lethal.

• Pathology: ECG helps diagnose irregularities like:

  • Elongated QRS means ventricle depolarization is taking too long
  • Elongated ST, repolarization problems.

Cardiology Case study

• Mrs. R is an 80 year old female.
• Her normal resting heart rate (HR) is 85 bpm.
• She normally exercises in the morning on a tread mill. One day on using the tread mill, she felt she had little energy and couldn’t do the exercises.
• She went to go see her cardiologists who found she had a 30 bpm heart rate. She has bradycardia, is it due to athletic training? No, usually it is 85 bpm.
• An ECG was generated:
  • P wave is normal
  • QRS is normal
  • QRS wave is occurring away from the P wave
  • R-R intervals is longer than P to P interval. Implies QRS is uncouples from P. So atrial and ventricle paces are different.
  • Seems like atria and ventricle contraction is independent. Points to an issue with the AV node.
  • The pacemaker is making the 30 bpm, possible pacemaker is actually the His bundle or Purkinje.

Key Concepts

1. The heart is a muscular organ which can contract in a rhythmic manner without direct stimulus from the nervous system because of the activity of pacemaker cells. The action potentials of the pacemaker and contractile cells of the heart differ. The pacemaker cells have an unstable resting membrane potential. In the heart, the SA node is the fastest pacemaker cells and sets the rate of beating. Other pacemakers are found within the electrical conduction system and include the AV node, bundle of His and Purkinje fibers.
2. Heart rate is determined by the input from the parasympathetic (PNS) and sympathetic (SNS) nervous systems. PNS activity slows heart rate; SNS speeds heart rate. At rest the normal heart rate is 70-80 beats per min.
3. The ECG is the sum of the electrical activity of the entire heart. The P wave correlates to atrial depolarization. The QRS complex correlates to ventricular depolarization. The T wave is the repolarization of the ventricles. Rhythm is determined by the SA node.
4. Disease of the electrical conduction system in the heart is manifested by change(s) in the ECG. e.g. timing, wave intervals, whether a specific wave occurs

Heart as a Pump

Generates pressure to lungs and circulatory system

Systole = pump of blood

Diastole = relaxing heart, filling with blood

Heart Chambers

Base of heart has cardiac skeleton

2 valves between atria and ventricles

Blood moves from right to left = amount of blood moving from lungs

Right atrium pressure - 10 mmHg

Right ventricle - 25 mmHg

Left atrium pressure - 15 mmHg

Left Ventricle pressure - 120 mmHg (large pressure to the pumping into aorta

 

Blood flow of heart: right atrium >valve> right ventricle >valve> lung > left atrium >AV valve> left ventricle >valve> aorta

Pulmonary means relating to the lungs

Cardiac Valves

Cardiac Cycle

1. Ventricle fill, passively, relaxed
2. P wave
3. AV valves close, isovolumic contraction which means pressure will increase due to restricted volume - depolarization of the ventricles, QRS wave
4. Systole: contraction of ventricle
5. Aortic valves & pulmonic valves open, ejection of blood
6. All valves close, pressure is falling, T wave
7. Isovolumic relaxation
8. Diastole: relaxation and filling, diastole lasts longer

Looking at the ECG and Cardiac Cycle - Wigger’s diagram

Only for left ventricle which pumps blood to aorta / body

Heart sounds: LUB - DUB

LUB = AV valves are shut, blood hitting against valve doors. Blood flow back into the valve making the sound after flowing into the ventricle.

DUB = Aortic valve is shut, same situation with blood in left ventricle hitting the valve.

Pressure-Volume Loop

Another look at pressure changes in left ventricle

1. A, ventricle has 50 mL
2. B, ventricle has been passively filled to ~100 mL = end diastolic volume (EDV). It is the volume just before systole.
3. C, pressure increase, from isovolumic contraction
4. D, aortic valve opens, from isovolumic relaxation = end systolic volume (ESV). There is always blood in the heart

Stroke volume (SV) = EDV - ESV

In this example SV = 90 - 50 = 40 mL

Cardiac Performance

Cardiac Output

The amount of blood pumped in an amount of time depends on the body’s needs. e.g. exercise requires more output.

Athletes may have low heart beats, but their cardiac output is about the same as others. So that means, an athlete’s stroke volume is higher than normal. It is because an athlete’s heart will be larger, thicker walls, and bigger chambers.

This larger heart allows a larger variance of cardiac output during performance due to high heart rates.

Key Concepts

• The heart consists of two separate pumps that move blood in a unidirectional manner tyhrough the pulmonary circulation for gas exchange and then to the systemic circulation for the delivery of O2 and nutrients and removal of waste products.
• Each beat of the heart (cardiac cycle) involves the electrical activation of the atria and ventricles, contraction and relaxation of those chambers, closing and opening of the cardiac valves and filling and emptying of the atria and ventricles. The sequence is the same for the right and left chambers.
• Ventricular contraction and ejection occur during systole. The beginning of the systole coincides with the first heart sound and ends with the 2nd heart sound.
• Ventricle relaxation and filling occur during diastole. Diastole begins with second heart sound and ends with the first heart sound.
• The volume of blood ejected with each beat is the stroke volume.
• The sum of the stroke volumes ejected in one minute is the cardiac output.

Cardiac Performance

Cardiac Output / Performance

Most people have the same cardiac output at rest ~ 5 Litres / minute

Strong hearts have an ejection fraction of about 50-75%, weak hearts (gained in size, but not strength) will have lower ejection fractions.

Cardiac Performance

Heart A is typical volumes

Heart B is its ventricle volumes enlarged so that at diastole, volume is around 140 ml

Venous Return and Contractility

Frank-Starling relationship

Heart is unable to recruit more muscle fibers like skeletal muscle because heart is using all fibers due to gap junctions. Stretching of cardiac myocytes will give better contraction.

Higher EDV increases SV. The ventricles are stretched through venous return (also referred to as preload).

The more blood in the ventricle at diastole, the higher the stroke volume.

Mechanisms that Increase Preload

1. Skeletal muscle contraction - squeezing veins to push blood back to heart.
2. Respiratory pump - big breaths decrease pressure in chest area allowing stretching of heart.
3. Increase blood volume - doping means blood is taken from an individual at a prior time (e.g. 0.5 L taken out). At a later time, the blood is injected back into the individual via blood transfusion (e.g. increasing total blood volume to 5.5 L). Increases the ability to carry oxygen with more red blood cells and enhances delivery of blood to tissues.
   1. It is illegal due to unfairness to athletes.
   2. Blood viscosity (hyper-viscosity syndrome): It increases viscosity of blood as person sweats since the person now has more blood cells per unit volume of blood and makes it harder on the heart and can be dangerous to cardiovascular system.
4. Vasoconstriction (sympathetic nervous system) - arteries are constricted and squeezes blood into the veins, increases flow of blood to heart.

Afterload is the tension or stress developed in the wall of the left ventricle during ejection. In other words, it is the end load against which the heart contracts to eject blood. Afterload is readily broken into components: one factor is the aortic pressure the left ventricular muscle must overcome to eject blood.

SNS Increases SV and Contractility

Ionotropic agent = they increase contractility of cardiac muscle.

Example ionotropic agents are epinephrine and norepinephrine

• The chart below shows resting state of the heart and the top line indicates heart activity after ionotropic agent is administered OR there is sympathetic activity.
• On the top line, stroke volume is increased since heart contractility is increased. i.e. entire muscle cell is more sensitive to Calcium and contraction is improved.

SNS increases cardiac output by increasing heart rate, stroke volume (via end diastolic volume).

Circulatory (CV) System

System as a whole

Muscular arteries have more muscles in walls.

Aorta and elastic, musclar arteries are high pressure.

Arterioles deliver blood to organs.

Capillaries allow exchange with tissues.

Veins have the largest capacity, most blood is in the veins at any given time. They are low pressure, high capacity.

Rules for the CV System

• Unidirectional, flow is from high to low pressure states.
• Causes of higher blood viscosity = blood doping, dehydration (these are rare states).
• Blood velocity will be slow in capillaries to allow time for exchange during diffusion.

Pressure and Pulsatility

Average systole pressure = 120 mmHg

Average diastole pressure = 80 mmHg

Compliance is equal to change in volume / change in pressure.

Arterioles like spigots

Pulsatility (pulse based differences in pressure) of blood is high in the aorta and elastic/muscular arteries. It is still present in the arterioles and starts to drop off in the capillaries and vein systems.

Notice blood pressure and pulsatility drops as it moves to the system.

Example, when getting a large cut on your wrist:

• If blood is squirting, you’ve cut an artery.
• If blood is oozing, you’ve cut a vein.

Blood Pressures

Mean Arterial Pressure (MAP)

Diastolic pressure (DP)

The heart stay longer in diastole than in systole, so the MAP is weighted to diastolic pressure.

Artery Regulated Blood Flow to an Organ

Blood is distributed in parallel tracks for organs. Note that the body doesn’t actually have enough blood to service all organs. If all capillary tracks were open, we would pass out due to lack of blood for all organs.

Two organ systems that always get 100% of blood (100% perfusion) is heart and brain. Skeletal muscle and GI tract may get low amounts depending on situations (digestion, exercise, sleep, etc.)

P2 - P1 = pressure gradient

Since vein pressure is usually low, in calculations the P vena cava or organ’s venous pressure can be considered approaching zero as indicated in the equations below.

As a result, the pressure gradient is considered to just be the MAP in the calculations below and would be divided by total peripheral resistance or organ pressure respectively.

Arterioles Regulate Blood within Organs

• Myogenic response is when wall tension changes, the cells stretch and contract.

• Hyperemia is when there is change in interstitial space (e.g. ECF metabolites like protons K, etc.) such as changes in skeletal muscle. Local arterioles will dilate and allow more blood flow.

  • Active - Perfusion is flow of blood to organs.
  • Reactive - Ischemia is when not enough oxygen is flowing to organs. An example is a blood pressure test which reduces/stops flow of blood in brachial (arm) artery. This test causes an ischemic event. In reaction, there is reactive hyperemia to allow higher flow to wash out metabolites.

• Reflex:

  • Sympathetic - norepinephrine is the neurotransmitter that acts on smooth muscle of arterioles.
  • Hormones - constrict (vasopressin acts on ADH, epinephrine acts on alpha 1 AR) or dilate smooth muscle

Arterioles Act as “Nozzles”

Arterioles can be contracted or relaxed like a nozzle that changes the flow rate.

Vasodilation causes increased flow to capillary, raising capillary pressure

Vasoconstriction causes less flow to capillary, lower capillary pressure

Exchange Across Capillary

• Pressure gradients exist and govern filtration and reabsorption rates.
• Hydrostatic pressure (HP) - The pressure exerted by a fluid at equilibrium at a given point within the fluid, due to the force of gravity. Hydrostatic pressure increases in proportion to depth measured from the surface because of the increasing weight of fluid exerting downward force from above.
• Oncotic pressure (OP) - or colloid osmotic pressure, is a form of osmotic pressure exerted by proteins, notably albumin, in a blood vessel’s plasma (blood/liquid) that usually tends to pull water into the circulatory system.
• Note
  • when HP > OP, there is a net filtration causing exchange from capillary to interstitial space.
  • When HP < OP, there is reabsorption (blood absorbs solutes)

Example: hypertension

• HP is high, OP remains the same as normal.
• Filtration occurs normally around arterioles and capillaries.
• Unfortunately, venules also have high HP, where HP > OP, block reabsorption. Then a pooling of fluid occurs in vasculature called edema.

Example: hypotension

• HP is low, OP remains as normal
• There is reabsorption all along capillary bed.

Lymphatic System

What about extra fluid around capillaries and tissues?

Typical day = 3L of blood returned to the blood.

Lymph nodes drain over time. Pathology: when lymph nodes are disrupted, fluid cannot drain properly back to the blood. To help move the fluid back to circulatory system, massaging and stimulation/exercising of drainage areas is required (e.g. breast cancer may cause disruption to lymph nodes near arms. To get lymphatic system working, massaging of arms and exercise will be required).

General Concepts

• Heart consists of two pumps. The pressure generated by the heart drives the unidirectional flow of blood through the pulmonary circulation where gas exchange occurs and through the systemic circulation where exchange of nutrients metabolites, heat, and hormones occurs.
• The vascular system is both a conduit for the flowing blood and a dynamic system that controls the distribution of the blood to the organs of the body. The distribution of blood is in parallel and certain paths can be shut depending on use except for brain and heart.
• Arteries are low resistance conduits and pressure reservoirs for maintaining blood flow during diastole. Arterioles are the dominant site of resistance to flow.
• Capillaries are the site of exchange. The balance of hydrostatic and oncotic forces determines the direction of fluid movement into or out of the capillaries.
• Veins are the low resistance conduits for venous return and volume reservoirs. Veins have high capacity (60% of body’s total blood).
• Sympathetic NS constriction of veins can increase venous return, thereby increasing SV and CO (preload).
• The lymphatic system provides a one-way route for the return of interstitial fluid to the cardiovascular system. This interstitial fluid is called lymph.
• Disease states that alter the hydrostatic and oncotic pressures can result in edema. These disease states include heart failure, liver disease, kidney disease and protein malnutrition.

Reflex Control

Reflex Loop

• Heart can control stroke volume (SV) and heart rate (HR).
• Preload can be control through venous return.
• Afterload - one factor is pressure required to overcome aortic valve.
• Medullary Cardiovascular Control Centre (MCCC) has a set point. Medulla can control pressure in reflex loop through SNS or PNS activation.
• Epinephrine and Norep. acts on the beta-1 adrenergic receptor (β1 adrenoreceptor / B1AR). B1AR also known as ADRB1, is a beta-adrenergic receptor, and also denotes the human gene encoding it.

Baroreceptor Reflex

Looking at receptors in reflex loop.

Example: Orthostatic hypotension — also called postural hypotension — is a form of low blood pressure that happens when you stand up from sitting or lying down. Orthostatic hypotension can make you feel dizzy or lightheaded, and maybe even faint.

• When lying down, blood is distributed evenly in body. When you spring up to do something from bed, blood is drawn by gravity down to feet. Baroreceptors in carotid sinus (neck) and in aortic arch (aorta) detect there is less volume and less stretch. The baroreceptors decrease firing, increasing sympathetic discharge activating Alpha-1 adrenergic receptors (A1AR) which causes vasoconstriction.

Example: blood pooling after standing at attention (e.g. palace guards) for too long a time.

Blood pools at the feet, eventually person becomes light headed due to insufficient blood to brain. After collapsing, the brain receives enough blood in the prone position and the person may wake up fine.

Other Receptors Influence Map

Chemoreceptors detect chemical changes for respiratory and CV systems.

Hypothalamus can control body temperature.

Example: hot day, system experiences dilation (capillary beds dilation) to help radiation of body heat outwards.

Conversely on a cold day, system experiences constriction.

Kidney controls fluid volume through excretion or retaining of fluid.

• Stretching of atria walls -> ANF causes hormone secretion indicated fluid should be lost
• Antidiuretic hormone (vasopressin), during dehydration, moves fluid from kidney tubules back to circulation. Urine would be concentrated.

Hemorrhage

• Situation: Extreme loss of blood, causing hypotension.

• Body tries to maintain cardiac output through increased HR, total peripheral resistance (TPR) - e.g. through vasoconstriction (ANGII, ADH), and increasing blood volume through release of fluid from kidney (aldosertone)

CO, TPR, & MAP in Aerobic Exercise

Situation: Running a marathon

Overview:

• Higher cardiac output (CO)
• Higher heart rate (HR)
• Increased flow of blood to skeletal muscle (around 80% of CO)
• Arterioles are dilated, TPR will decrease as capillary beds are dilated. Lots of perfusion.
• MAP is increased slightly.

What about Anaerobic exercise?

The anaerobic motion (like lifting weights) creates an ischemic event due to muscle contraction. Reactive hyperemia occurs and arterioles will dilate during relaxation.

• TPR will increase
• CO needs to be higher
• MAP will be higher.

What about baroreceptors during exercise?

Why don’t baroreceptors fight against changes in MAP? Before and during exercise, baroreceptors can reset their set point to a higher level. After exercise, baroreceptors will normalize their set points.

During hypertension, it is possible baroreceptors will be set at a chronically higher state (e.g. 130+ / 89+ systolic/diastolic pressure set points).

Heart Failure, Hypertension

For the weak heart, although we have improved preload, the afterload has increased and MAP is increased as a result.

Capillaries experience high hydrostatic pressure. There is a lesser absorption. Edema may result where blood pools in feet and ankles.

General Concepts

• Cardiac output is matched with tissue blood flow by maintaining constant mean arterial blood pressure (MAP). CO = MAP/TPR If CO goes down, TPR must rise to retain MAP.
• Baroreceptors act as short term regulators of arterial blood pressure by providing sensory information to the cardiovascular center in the medulla (MCCC). Autonomic outflow from the MCCC maintains blood pressure constant.
• Hemorrhage leads to reduced CO (hypotension) as a result of reduced ventricular EDV. The normal compensatory response to hemorrhage is vasoconstriction of arteries and capacitance veins and increased cardiac contractility and heart rate.
• Hypotension can also result from a sudden postural change or prolonged quiet standing (orthostatic hypotension). The compensatory response is stated above for hemorrhage.
• Failure of the left heart to maintain normal CO leads to an accumulation of blood in the lungs which inhibits gas exchange.
• Failure of the right heart to maintain normal CO leads to an accumulation of blood in the systemic veins, increased capillary filtration, and edema.
• Compensation for decreased arterial pressure caused by heart failure includes increases in HR and TPR, vasoconstriction of veins, and retention water by the kidneys.