Overview

The heart has 2 separate pumps

Left pump

• pumps oxygenated blood to the body (systemic circuit)

• consists of the left atrium, bicuspid valve, left ventricle and left atrium

  • pathway of left pump:

    • pulmonary veins → left atrium → bicuspid (left AV or mitral) valve → left ventricle → aortic semilunar valve → aortic trunk (right and left carotid artery & left and right subclabical artery) → body

Systemic circuit

• Arteries carry oxygenated blood

• Veins carry deoxygenated blood

Right pump

• pumps deoxygenated blood into the lungs (pulmonary circuit)

• consist of the right atrium, tricuspid valve, right ventricle and right atrium

  • pathway of left pump:

    • superior & inferior vena cava → right atrium → tricuspid (right AV) valve → right ventricle → pulmonary semilunar valve → pulmonary trunk → pulmonary artery → lungs

Pulmonary circuit

• Arteries carry deoxygenated blood

• Veins carry oxygenated blood

Diagrams

Right and left pathways

Exterior anatomy

5 vessels that emerge from the aorta

Coronary circulation

• Left coronary artery → supply blood to the left side of the heart

• Right coronary artery → supply blood to the right side of the heart

• Left anterior decreasing (LAD) coronary artery → located in interventicular sulcus

  • supplies blood to the front side of the heart

  • Also referred to as “widow maker”

    • LAD supplies the heart with fresh blood,

      • if blocked it can lead to…

        • ischema → low O2

        • infart → cell death

Coronary Artery disease (CAD)

Atherosclerosis

• arterial wall disease characterized by the development of an atheroma (or plaque) leading to arterial narrowing and impaired blood flow (perfusion)

  • atheroma → abnormal accumulation of macrophages, lipid, Ca2+, smooth muscle cell, and connective tissue in the tunica intima

    • LDL → cholesterol carrier

      • carries cholesterol to cell, too much is bad bc it carries cholesterol to parts we do not want (i.e. cell wall of veins/arteries)

Thromboembolism

• late stage atheromas can rupture and promote the formation of a thrombus (or blood clot) which exacerbates arterial narrowing, impaired perfusion and inschemia

  • embolus - free-floating thrombus broken loose from a vessel wall which can lodge in, and occlude, downstream, smaller vessels

  • major be the cause of…

    • (ischemic) stroke

  • potential cause of…

    • myocardial ischemia (cerebral infart)

    • myocardial infarction (heart attack)

  

CAD treatments

• lifestyle changes → exercise, stress-reduction, and healthy eating

• treatments →

  • thrombolytics

    • cloth busters

  • anticoagulants

    • aspirin (antiplaquet)

    • blood thinNers (NOACS/DOACS)

  • cholesterol medications

    • statins

  • negative inotropes

    • beta blockers

  • vasodialators (angina → chest pain)

    • nitroglycerine

  • PCSK9 inhibitors

    • erocumab

Corrective Procedures

ballon angioplasty

coronary stenting

coronary by-pass

• take segment of vein in leg and stitch it to the heart

Fetal Circulation

Special feature

• Foramen Ovale → this hole closes and turns into the Fossa ovalis

• Ductus arteriosus → closes and becomes ligamentum arteriosum

3 layers of the heart

• Dense fibrous layer

• Parietal pericardium

  • lose connective tissue

  • epithelium

• Pericardial cavity

• Epicardium

  • lose connective tissue

  • epithelium

• Myocardium

  • thicker on the left ventricle than the right as it need to pump blood to the entire body thus needs to generate a great ammount of energy.

    • the right pump only pumps blood 6inches away to the lungs

• Endocardium

  • lose connective tissue

  • endothelium

Cardiac Conduction system

• Heart cells (2 types) →

  • contractile cells (99%)

  • authotithmic cells (1%)

• subendocardial network of specialized authotithmic cardiomyocites cappable of generating and conducting APs

cardiac vs skeletal muscle

• cardiac muscle cells only have one or two nuclei while muscle cells are multinucleate.

• cardiac cells are involuntary controlled while skeletal are voluntarily controlled.

• cardiac are interconeccted by gap junction while skeletal are long and fused

• in cardiac cell DHPR (voltage-gatted Ca²⁺ channel) is used for depolarization while in cardiac its L-type Ca²⁺ channel

Cardiac Conduction Anatomy

Sinoatral node (SA node)

• its a small body of specialized muscle tissue that acts as as pacemaker by spontaneously producing a contractile signals (prepotential signals) that establishes heart beat

• located in the upper wall of the right atrium

• AP frequency → 70mph

Internodal pathway (fibers)

• cardiac conductive cells that emanate from the SA node and innervate the atrial myocardium and terminate at the atrioventricular (AV) node.

  • they conduct the prepotential signal from the SA node to the myocardial cells of the atria and the AV node

• located in right atrium

Atrioventricular (AV) node

• Electrically connects the right atrium and ventricle, it generated and conduces APs, also delays SA signal.

  • delays the SA signal for about ~100ms

• located in the floor of the right atrium

• AP frequency → 50mph

Purkinje fibers

• in charge to send the contraction signal to the the ventricular myocardium

• AP frequency → 30mph

Intercalated discs

• regions in cardiac tissue which contain a high density of gap junctions

  • Function syncytium

    • cardiomiocytes are interconnected by gap junctions, once a AP signal is sent it travels through the gap junctions spreading through the cells making them contract in unison

Cardiac Conduction signal process

Step by step

1. SA is depolarized and produces the AP signal

2. AP signal travels through the intermodal fivers to the AV node

3. AV node delays the signal (~100ms)

4. signal travels through the bundle of His

5. the bundle of his splits into the right and left branches of His

6. the signal travels through the branches

7. the signal is directed through the moderator band which stimulates the papillary muscle in the ventricles and then propagated up the Purkinje fibers

What if there is a derailment?

• if one cell derails the next one with the highest rate of prepotentials takes over '

  • (condition): derails → takes over

    • Sick Sinus Syndrome: SA node (70mph) → AV node (50mph)

      • low heartbeat

      • can live but in some casses migh require the need of a pacemaker

    • Complete Heart Block: AV node (50mph) → Purkinje fibers (30mph)

      • Due to AV node being derrailed the SA derrails as well making the Purkinje fibers be the peacemakes.

      • may cause the person to faint with injury, low blood pressure, and damage to other internal organs, and cardiac arrest

      • treatment → pacemaker

    • Ventricular Tachycardia: non-cardiac cells send signals to the Purkinje fibers making them rapidly fire signals

      • heart beats too fast to pump well and the body doesn't receive enough oxygenated blood

        • may lead to fainting

        • can be caused by things such as caffeine (stimulants)

Autorythmic ( cardiomyocites

Slow cell AP (SA & AV nodes)

• the pacemaker cells (SA & AV nodes) are auto-rhythmic (self-exitatory)

  • in other words they can spontaneously generate APs (in this case they are referred as pre-potentials) without innervation

• Resting membrane potential (RMP)→ -60mV

• Threshold Potential (TP) → -40mV

Phase 0 → depolarization phase

• beguins after threshold potential is reached

• At around -40 mV, L-type (iCa⁺,(L)) calcium channels open up and allow the steady flow of calcium into the cell

• this influx of calcium depolarizes the cell

Phase 3 → repolarization phase

• at +30 mV voltage-gated potassium channels (iK1) open creating a outflow of K⁺ from the cell through them

  • potassium current

• At some point during the end of the phase, when the depolarization reaches -40mV iK1 close and the funny channels open

Phase 4 → pre-potential phase

• funny channels open allowing Na⁺ in making the cell repolarize back to RMP and subsequently TP to go into phase 0 again

Contractile cardiomyocites

Fast cell AP (Ventricular Cardiomyocyte)

• any other cardiac cell that is not the AV or the SA

• Resting membrane potential (RMP)→ -90mV

• Threshold Potential (TP) → -70mV

Phase 0

• constant leaking of K⁺ from iK channels maintains the cell at RMP

  • makes it be at equillibrium potential with K⁺

• the depolarization of an adjacent cells make voltage-gated sodium channels (iNa⁺) open allowing Na⁺ to go into the cell

  • the cell depolarizes FAST as Na⁺ comes in

Phase 1

• at +30 mV voltage-gated potassium channels (iK) making potassim leak out the cell

  • Slightly depolarizes the cell

Phase 2

• at -55mV iCa⁺,(L) channels open, allowing Ca⁺ in

• this influx of Ca⁺ balancess the Na⁺ with the K⁺ leaking out

  • influx → Ca⁺

  • efflux → K⁺

• this creates the plateau

Phase 3

• eventually the first iK⁺ channels close and other iK⁺ channels open allowing K⁺ to fully leave the cell making it repolarize

Excitation-contraction coupling

Cardiac vs skeletal

• In cardiac muscle the contraction is triggered by electrical
  signals from neighboring cells. The ANS modulates the response.
  Excitation-contraction coupling is mediated by a phenomenon referred to
  as calcium-induced calcium release

What is calcium-induced calcium release?

• Calcium-induced calcium release is when calcium is able to
  enter the sarcoplasm via DHPR to bind to and activate RyR and cause
  calcium release into the sarcoplasm.

what are funny channels?

• The funny channels are activated by repolarization and cAMP.

  • Sympathetic innervation increases cAMP, which binds to funny channels and increases the probability that they are open.

  • Parasympathetic innervation decreases cAMP, which is now unbound to funny channels and therefore decreases the probability that they are open.

Atrial and Ventricular Cardiomyocytes

Semilunar valves

• Semilunar valves are inherently one-way valves meaning they
  only open in one direction, without the assistance of papillary muscles and
  chordae tendineae.

Atrioventricular (AV) velves

• AV valves are not inherently one-way valves because they
  require papillary muscles and chordae tendineae to function properly.

  • Wow do they work together?

    • Papillary muscles contract prior to the ventricles contracting to
      reduce the travel of the AV valves so that they properly shut. The papillary muscles are attached to chordae tendineae, which are also attached to the flaps of the AV valves.

      • when the ventricles are relaxed the AV valves are open allowing blood to pool into the ventricle

        • passive ventricular fill

  • What if the chordae tendineae were severed?

    • If chordae tendineae were severed the AV valve would prolapse
      and potentially lead to atrial regurgitation.

  • Top hat Q: papillary muscless contract to…

    • …prevent the AV valves from opening into the atria

Mitrial (bicuspid) valve

Cardiac Electrophysiology

The Electrocardiogram (ECG)

what is it?

• body surface recodring of the heart’s electrical events occurring within the heart

  • correlated with the mechanical events of the heart

ECG waveform

Components

• P-wave → atrial depolarization

• PR segment → atrial contraction (systole)

  • AV node delay

• QRS complex → simultaneous atrial repolarization and ventricular depolarization

• ST segment → ventricular contraction (systole)

  • time during which ventricles are contracting and emptying

• T-wave → ventricular repolarization

• TP interval → time during which ventricles undergo passive ventricular fill

• RR interval → heart rate

Cardiac Arrythmias

Tachycardia

• A heart rate of more than 100 hpm

• During tachycardia, the RR interval decreases in length

Sinus Tachycardia

Ventricular Tachycardia (VT, Vtach

Supraventricular Tachycardia

Bradycardia

• a heart rate that is equal or less than 60 hpm

• During bradycardia, the RR interval increases in length

• Can someone be clinically bradycardic and still considered to have a normal heart rate?

  • Yes, you can be clinically bradycardic and be considered to have
    a normal heart rate. A slow heart rate does not cause any problems.

    • Bradycardia can be a sign of being very fit.

    • Healthy young adults and athletes often have heart rates of less than 60 beats per minute.

Sinus Bradycardia

Premature Contraction

Premature Ventricular Contraction (PVC)

• During a PVC, the ventricles contract before the ST segment, making the QRS complex abnormal.

Premature Atrial Contraction (PAC)

• During a PAC, the TP segment is shorter because the P wave is occurring prematurely.

Fibrillation

ventricular fibrillation

• During ventricular fibrillation, the QRS complex decreases in size
  and the signal is noisy.

atrial fibrillation

• During atrial fibrillation, the P waves in the ECG are absent and the signal is noisy

Complete Heart Block

• In complete heart block, QRS complexes may be missing and
  the signal is conducting slowly due to a blockage

ST segment

ST segment elevation

• An ST segment elevation is transmural, or full thickness, ischemia and indicative of a myocardial infarction

ST segment depression

• An ST segment depression results from subendothelial partial thickness ischemia

  • indicative of coronary artery disease

Cardiac Cycle

• period of mechanical events of the heart between the start of one heartbeat and the start of the next

Phases:

• Systole → contraction phase

• Diastole → relaxation phase

• Does the heart spend more time during systole or diastole?

  • The heart spends more time in diastole (specifically, the heart
    spends 2/3 of the cardiac cycle in diastole)

Events:

• atrial systole → atrial contraction

  • atria contracts and and fill the relaxed ventricles with an additiona ammount of blood

    • they are already 75% filled with blood

• atrial diastole → atrial relaxation

• ventricular systole →

  • early → isovolumetric ventricular contraction

    • the ventricles contract isovolumetrically or in other words while they are contracting the, pressure within the ventricle is not great enough to open the semilunar valve

      • this contractions push the AV valves close

      • AV → closed

      • Semilunar → closed

  • late → rapid ejection

    • pressure keeps rising untill it is creater than the pressure in the arteries, opening the semiluner valves and rapidly ejecting blood

      • AV → closed

      • Semilunar → open

• ventricular diastole

  • early → isovolumetric ventricular relaxation

    • pressure in ventricle drops; blood passively flow into the atria and against the cusps of semilunar valves forcing them shut

      • AV → closed

      • Semilunar → closed

  • late → passive ventricular filling

    • all chambers of the heart are relaxed allowing blood to passibly fill the ventricles

      • this is where the 75% already full comes from

      • AV → open

      • Semilunar → closed

Mechanical (M) & electrical (E) events of the heart

• Start

  • E: pre-P-wave → SA node depolarization

  • E: P-wave → atrial depolarixation/AV nde depolarization

• PR segment →

  • M: atrial systole

  • E: AVN delay (100ms)

  • E: His/Purkinje depolarization

• QRS complex→

  • E: atrial repolarization

  • M: Atrial diastole

  • E: ventricular depolarization

  • M: ST-segment → early ventricular systole (IVC)

• ST-segment →

  • M: late ventricular systole (rapid ejection)

• T-wave →

  • E: ventricular repolarization

  • M: TP-interval → early ventricular diastole (IVR)

• TP-interval →

  • E: no activity

  • M: late ventricular diastole (passive ventricular filling)

Wiggers diagram

• shows the pressure changes within the heart during the cardiac circle

How does this diagram differ between the left and right sides?

• in the right ventricle there is not that much pressure generated, since blood is pumped to the lungs so the pressure loop is shorted than that of the left ventricle which pumps blood to the entire body.

Sounds of the heart

• “lubb” → closure of AV valves

  • occurs at 3

• “dubb” → closure of semilunar valves

  • occurs at 6

Cardiac Hemodynamics

Cardiac Hemodynamic Parameters

Cardiac output (CO)

• the volume of blood pumped by each ventricle of the heart per minute

  • the heart pumps 5L of blood to the body per minute

• can increase during exercise to 20-40 L/min

ANS (autonomic nervous system) control of CO

• cardiac output = heart rate * stroke volume (CO=HR*SV)

  • cardiac output is dependent on HR and SV

Heart Rate (HR)

• how many time a heart beats per minute (bpm)

  • ~70 bpm

• Ranges:

  • Normal → 60-100 bpm

  • Bradycardia → <60bpm

  • Tachicardia → >100 bpm

  • Intrinsic rate → 100-110bpm

  • upper limit → ~220 bpm

ANS controll of HR

• heart is innervated by both arms of the ANS

  • Sympathetic (SNS)

    • primary innervate the SA and AV nodes, and contractile cardiocytes

      • increases HR (increase chronotropy) and dromortopy

      • during exersise, increases HR due to an initial rapid withdrawal of PNS activity

      • SNS acctivity → NE → Beta 1 → increase AC → increase cCamp → increase iF (funny current) → increase phase 4 slope → increase HR

      • SNS activity → EPI

  • Parasympathetic (PNS)

    • The ANS modulates the heart rate by the sympathetic and parasympathetic branches. Stimulation of the sympathetic branch increases heart rate, and stimulation of the parasympathetic branch decreases heart rate

    • primary innervate the SA and AV nodes

      • at rest PNS activity dominares SNS (Vagal tone)

      • during exersise HR increases due to an initial and rapid withdrawal of PNS (a release of the vagal break) and subsequen increase in SNS activity

      • PNS acctivity → Ach → M2 → decrease AC → decrease cCamp → decrease iF → decrease phase 4 slope → decrease HR

There is a “vagal brake” on the heart. What does this mean and how does the brake work?

• The SA node is innervated by the vagus nerve. It drips acetylcholine onto the pacemaker, slowing heart rate. When vagal tone to the heart’s pacemaker is high, a baseline or resting heart rate is produced.

  • In other words, the vagus nerve acts as a restraint, or brake, limiting heart rate

  • more ACth = slower HR

What is a funny channel?

• The funny channels are activated by repolarization and cAMP.

  • Sympathetic innervation increases cAMP, which binds to funny channels and increases the probability that they are open.

  • Parasympathetic innervation decreases cAMP, which is now unbound to funny channels and therefore decreases the probability that they are open.

Stroke volume (SV)

• volume of blood pump out of each ventricle of the heart during each beat

  • ~70ml

  • can increase during exercise to 120-180ml

  • Contractility in how hard and fast myocardial cells are contracting.

    • Increases in contractility increase stroke volume.

    • An increase in contractility will decrease end systolic volume and increase stroke volume.

What controlls it?

• SNS control of SV

  • extrinsic control

    • increase SNS → increase in β1-adrenergic activation → increase cardiac contractile force

      • Contractility in how hard and fast myocardial cells are contracting.

        • Increases in contractility increase stroke volume

  • intrinsic

    • ncrease SNS → increase cardiomiocyte relaxation rate (lustriopy) → increase venous return to beart (Frank–Starling law of the heart)

calculations

• SV = EDV – ESV

  • end-diastolic volume (EDV) is the volume of blood in the ventricles at the end of passive ventricular filling.

    • This is approximately 120 mL

  • end-systolic volume (ESV) is the volume of blood in the ventricles at the end rapid ejection.

    • This is approximately 50 mL

Frank-Starling effect

• The Frank–Starling law of the heart states that the stroke volume
  increases in response to an increase in the volume of blood filling the
  heart. Increases in preload will increase stroke volume

ejection fraction (EF)

• EF is the fraction of blood ejected from a ventricle of the heart
  with each heartbeat.

  • A normal ejection fraction value is approximately 55%.

    • Below that indicates heart failure.

calculations

• EF = SV / EDV

  • SV → stroke volume

  • EDV → end-diastolic volume

    • normal → 55-75%

    • absnormal → <40%

Heart Failure

• Heart failure with a reduced ejection fraction (HFrEF) → occurs when the ejection fraction is below 40%.

  • The heart is too weak to pump properly

• Heart failure with a preserved ejection fraction (HFpEF) → occurs when the heart is too stiff to pump properly. The ejection fraction, in this case, is normal

preload and afterload

preload

• the blood return venously to the heart

• How do changes in preload affect EDV, ESV, and SV?

  • An increase in preload will increase EDV, decrease ESV, and
    increase SV.

afterload

• the blood within the arteries that blood being pumped from the heart has to push against

• How do changes in afterload affect EDV, ESV, and SV?

  • An increase in afterload will decrease SV and increase ESV

Circulation

anatomy

Veins

• Veins have 3 layers, valves and are more superficial in the subcutaneous tissue.

Artery

• Arteries have 3 layers, prominent smooth muscle, no valves and
  are deeper in the subcutaneous tissue.

Microcirculation

• It is the part of the vascular system and consists of the small
  vessels called arterioles, capillaries, and venules.

Functions

• arterioles → resistance

  • control your blood pressure and blood flow throughout your body, using their muscles to change their diameter.

  • link to capillaries to exchange oxygen, nutrients and waste

• venules → capacitance

  • smallest veins and receive blood from capillaries.

  • Also play a role in the exchange of oxygen and nutrients for water products

• capillaries → exchange

  • have thin walls to facilitate exchange

    • Oxygen and nutrients from the blood can move through the walls and get into organs and tissues.

    • also take waste products away from your tissues.

Measuring blood pressure

• When blood pressure is taken, it is reported as a “top number” and a “bottom number.” What do these numbers represent?

  • The top number represents the systolic blood pressure

  • The bottom number represents the diastolic blood pressure

• normal blood pressure value → 120/80

• Mean arterial BP (MAP) = [(2*DBP)+SBP]/3

How to measurre BP using a sphygmomanometer and a stethoscope

• The cuff is inflated above 120 mmHg to stop arterial blood flow.
  As the cuff is deflated, Korotkoff sounds are generated by turbulent blood flow through the brachial artery.

  • The first instance of these sounds is systolic blood pressure.

  • What are the Korotkoff sounds?

    • Korotkoff sounds are the sound of blood flowing turbulently through the artery.

      • Korotkoff sounds are absent when the brachial artery is fully patent, and flow is laminar.

      • When the Korotkoff sounds cease, that is diastolic blood pressure.

How is pulse pressure calculated?

• difference between the systolic and diastolic pressure

How is pulse measured and what is a typical value?

• Pulse is typically measured by placing the tips of your index and middle finger on the radial artery at the wrist.

  • A typical value of a pulse is 60-100 beats per minute

Chronic hypertension

• Antihypertensive medications

  • beta 1 blockers → metoprolol-Lopressor

  • alpha 1 blockers →