Cardiovascular System: Heart

Heart Characteristics

• relatively small, about the size of a closed fist

• Dimensions: 12 × 9 × 6 cm; 250 g (F) or 300 g (M)

• located within the thoracic cavity

• rests on the diaphragm near the midline

• lies within the mediastinum (between sternum and vertebral column, first rib to diaphragm, between lungs)

Heart Location and Shape

• about two-thirds lies to the left of the midline

• shape resembles a cone lying on its side

• Apex: tip of left ventricle, rests on diaphragm

• Base: opposite the apex, posterior aspect formed mainly by atria (particularly left atrium)

Heart Layers

from most superficial to most interior

1. Fibrous Pericardium: tough, protective sack, anchors heart in place, prevents overstretching

2. Serous Pericardium - Parietal: lines the inner surface of fibrous pericardium

3. Pericardial Cavity: contains thin film of fluid, reduces friction during heartbeat

4. Serous Pericardium - Visceral: also called epicardium, lies on surface of heart and made of mesothelial cells

   • Outermost: mesothelium, visceral serous pericardium

   • Innermost: fibroelastic & adipose

   • contains vessels (blood, lymph) and nerves supplying heart

5. Myocardium: thick layer consisting of cardiac muscles, contractile powerhouse, about 95% of wall

6. Endocardium: smooth endothelial surface, minimizes turbulence as blood moves through chambers

Layers 1-4 are covering

Layers 5-6 are actual heart wall

Inflammation of Layers of the Heart

Naming Convention: layer + itis

Myocarditis: caused by infections or drugs (hypersensitivity)

Infective Endocarditis:

• serious infection, involves lining and valves

• left valve = mitral; right valve = tricuspid

• can be acute or subacute

• Risk Factors:

1. Presence of prosthetic valve

2. Previous endocarditis

3. Congenital

4. Mitral valve prolapse with regurgitation

• most commonly caused by staphylococci

• but can be caused by streptococci

Heart Chambers

Atria:

• upper chambers, have thinner walls

• Right Atrium: receives deoxygenated blood from veins (superior and inferior vena cava, coronary sinus)

• Left Atrium: receives oxygenated blood from pulmonary veins

• atria pump blood into ventricles

Ventricles:

• lower chambers, have thicker walls

• Right Ventricle: pumps deoxygenated blood into lungs

• Left Ventricle: pumps blood to rest of the body

• left ventricle has thicker walls than right for this purpose

Valves and Valve Problem Terms

• act as gates between chambers

Atrioventricular Valves (AV):

• Between atria and ventricles

• Left AV Valve: Bicuspid/Mitral Valve

• Right AV Valve: Tricuspid Valve

Semilunar Valves:

• Pulmonary Valve: between right ventricle and pulmonary artery

• Aortic Valve: between left ventricle and aorta (main artery)

Chordae Tendineae:

• tendon-like chords the valves are connected to

• connect to papillary muscles

• supports and anchors the valve cusps in place

Stenosis: narrowing, does not fully open restricting blood flow

Regurgitation: valve fails to close properly, causing backflow

S1, S2, and S3

S1:

• end of the diastole, start of the systole

• sound is closing of the AV Valves

S2:

• end of the systole, start of the diastole

• sound is closing of the Semilunar Valves

S3:

• ventricular gallop

• abnormal sound caused by regurgitation

Serotonergic Psychedelic Effects

• ex: LSD, MDMA

• act as serotonin agonists

• chronic or high-dose activation of receptors has been liked to valvulopathy

• Valvulopathy: condition where one or more of the four valves do not open or close properly, can lead to regurgitation and embolism

• receptor activation can also cause pericardial fibrosis (walls thicken)

Valvular Disease Causes

can be seen in many conditions

ex:

• Drug Induced (5-HT_2B agonists)

• Endocarditis

• Rheumatic Fever

• Other Heart Diseases

Ductus Arteriosus

• a fetal structure

• fetus has yet to develop lungs to breathe, oxygen is acquired from mother’s placenta

• oxygenated blood obtained from umbilical vein

• blood must then bypass lungs

Ductus Arteriosus:

• temporary fetal blood vessel that connects pulmonary artery and aorta

• closes shortly after birth (hours to days)

• kept patent (open) by Prostaglandin E2

Patent Ductus Arteriosus: kept open after birth causing problems

Broken Heart Syndrome

• also called takotsubo cardiomyopathy or apical ballooning

• upon great stress, heart ends up ballooning

• reversible

Systemic and Pulmonary Circulation

1. Deoxygenated Blood from superior and inferior vena cava and coronary sinus enters right atrium

2. Tricuspid valve opens, allowing blood to flow to right ventricle

3. Pulmonary valve opens, allowing blood to flow through pulmonary artery into lungs

4. Blood flows through pulmonary capillaries, losing CO₂ and gaining O₂

5. Oxygenated blood flows through pulmonary vein into left atrium

6. Bicuspid/Mitral Valve opens allowing blood to flow to left ventricle

7. Aortic valve opens letting oxygenated blood flow into aorta

Blurry Umi judges you for your sins

Coronary Circulation

• the heart wall needs own blood supply

• branches from ascending aorta

Coronary Arteries:

• left and right

• supply blood to the myocardium, and facilitate gas exchange through capillaries

Coronary Veins:

• great, middle, small, and anterior

• carries deoxygenated blood back into coronary sinus (which then brings them back to right atrium)

Chest Pain Related Terminologies

Chest Pain:

• can be cardiac or non-cardiac

Angina: chest pain or discomfort due to myocardial ischemia (insufficient heart blood supply)

Ischemic Heart Disease or Coronary Artery Disease (CAD):

• narrowing or blockade of coronary arteries, cutting off blood supply

• causes: plaque formation, etc

• stable angina: causes pain on exertion

Acute Coronary Syndrome:

• when myocardial oxygen demand exceeds oxygen supply

• leads to myocardial infarction (blocked blood flow which leads to irreversible cell death)

• increased cardiac troponin in blood suggests heart muscle injury

• also diagnosed with ECG changes and imaging

ACS can be further categorized into

• Non-ST-Elevation ACS: unstable angina at rest

• Non-ST-Elevation Myocardial Infarction: inner ventricle wall cells begin to die; partial blockage

• ST-Elevation Myocardial Infarction: infarction extends to entire thickness of myocardium; complete blockage

note: syndrome means combination of signs and symptoms

Revascularization

• process where after heart blockage occurs, new vessels are made to provide alternative flow

• the faster that occurs, the lower the risk of cardiac death or heart attack

Cardiac Muscle Tissues

Cardiac Muscle Tissue:

• connected by intercalated discs

  • linked by desmosomes (for mechanical strength) and gap junctions (for rapid electrical communication)

• Autorhythmic Fibers are self-excitable, can generate own action potentials (pacemaker cells)

Cardiac Conduction System

To beat, the heart sends action potentials across itself in a set order and flow

Sinoatrial (SA) Node:

• the start of the pulse, triggers every 0.6 seconds

• found in upper right atria

• heart’s natural pacemaker

• contain the cells that self-depolarize the fastest

• flows down gap junctions until hitting AV node

Atrioventricular (AV) Node:

• located above tricuspid valve

• slower than SA node, delays the pulse

• allows atria to contract before ventricles contract

Atrioventricular Bundle:

• also called AV Bundle or Bundle of His

• the path the pulse takes to the bottom of the heart

• branches out into right and left ventricles via left/right bundles

Purkinje Fibers:

• widespread, spreads the pulse to the rest of the ventricles

At a molecular level, the ionic basis of depolarization differs based on location

In the Event of SA Node Damage

• if the SA node is damaged, the AV node will take over

• if the AV node is damaged, the AV Bundle will take over

• for every node damaged, the cycle gets slower, because the succeeding nodes are slower

Details on Nodes

SA and AV Nodes:

• are also called slow response tissues

• action potentials differ significantly from muscle cells in atrioventricular tissue

• slow activation

• higher threshold voltage

• higher resting membrane potential (around -60 mV)

Phases of Nodal Action Potential

1. Phase 4:

   • spontaneous depolarization

   • activates when membrane hyperpolarizes

   • open sodium channels allow sodium into cell, slowly depolarizes cell

   • this is called Inward Funny Current (or If)

   • gradually, T-Type Calcium Channels open, calcium flows inward, further depolarization

2. Phase 0:

   • upon reaching a certain threshold, L-Type Calcium Channels open causing even further depolarization

   • If and T-Type Ca start to close

3. Phase 3:

   • repolarization

   • Potassium Channels allow escape of potassium, causing cell to become more negative

   • Calcium channels close

   • eventually, cell hyperpolarizes, which will trigger Phase 4 again

Phases of Ventricular Action Potential

particularly important for anti-arrhythmias

1. Phase 0:

   • large influx of sodium ions through fast sodium ion channels (INa)

2. Phase 1:

   • sodium channels close upon reaching a threshold

   • transient efflux of potassium ions through slow open potassium channels

   • causes slight repolarization

3. Phase 2:

   • slow L-Type Calcium Channels (slow to open and close) open

   • calcium flows in as potassium flows out

   • calcium influx also causes potassium permeability to decrease

   • creates a plateau until the calcium channels close again

4. Phase 3:

   • plateau ends, potassium quickly effluxes

   • cell quickly repolarizes

5. Phase 4:

   • inward rectifier potassium current returns charge to resting potential

Arrythmia

• regularly irregular heartbeats

• abnormal rhythm caused by problems with the cardiac electrical system

• normal heart rate: 60-100 bpm

• Tachycardia: too fast; > 100 bpm

• Bradycardia: too slow; < 60 bpm

Tachyarrhythmias:

• related conditions: sinus tachycardia, atrial fibrillation, Torsades de Pointes (TdP)

Bradyarrhythmias:

• related conditions: sinus bradycardia, sick sinus syndrome, conduction blocks

Boboiboy Earth

QT Interval Prolongation

QT Interval: section of EKG that represents the total time for ventricular depolarization and repolarization

• essentially, represents the total time for the ventricles to contract and then rest

• shorter = higher heart rate

• longer = slower heart rate

Prolongation means repolarization is delayed

• may cause Torsades de Pointes (TdP) also known as Polymorphic Ventricular Tachycardia

• which may then lead to cardiac death

Genes Related to QT Interval Prolongation

Gene: KCNH2 gene

• related to potassium voltage gated channel

• codes for hERG subunit

• full channel is the Kv11.1 Channel through which IKr flows

• most cases of acquired QT-Prolongation, this channel is blocked

Systole and Diastole

Diastole:

• period where ventricles relax

• allow AV Valves to open

• blood flows from high-pressure atria to low-pressure ventricle

• S1: heart sound, the closing of AV valves (the lub)

Systole:

• period where ventricles contract

• allow Semilunar valves (SL) to open

• blood flows into pulmonary and systemic arteries

• S2: heart sound, the closing of the SL valves (the dub)

S3 Gallop:

• abnormal heart sound caused by regurgitation

Cardiac Cycle

when heart rate is 75 bpm, and a cycle is 0.8 s

Atrial Systole (0.1 seconds):

• ventricles in diastole, hold around 105 mL blood in them already

• SA node → Atrial Depolarization → Contraction

• Ventricles gain 25 mL from pump, for a total of 130 mL (end-diastolic volume)

Ventricle Systole (0.3 seconds):

• atria in diastole

• ventricular contraction:

• first, isovolumetric contraction (squeezes, but no blood is pumped because valve is closed)

• then continued contraction increases pressure, valves open when threshold is met → ventricular ejection

• Around 70 mL is ejected to aorta/pulmonary trunk

• leaves around 60 mL behind (end-systolic volume)

Relaxation (0.4 seconds):

• ventricular repolarization, aorta relaxation

• both ventricles and atria are in diastole

• SL valves close

• Isovolumetric Relaxation: all valves close

• as ventricles relax, pressure drops causing AV valves to open

Stroke Volume and Ejection Fraction

Stroke Volume: blood ejected per beat, per ventricle

calculation: EDV - ESV

Ejection Fraction: (SV/EDV) x 100; measures ventricular efficiency

• Ejection Fraction > 50% is good

Cardiac Output

• or Stroke Volume per Minute

• Calculation: CO = Stroke Volume x Heart Rate

• Average: 70 mL/beat

• during exercise, heart rate and stroke volume increases so CO increases

Regulators of Stroke Volume

Regulators of Stroke Volume:

1. Preload:

   • degree of stretch of heart muscle before it contracts

   • higher end diastolic volume = more the myocardial fibers stretch

   • Frank-Starling Law: higher stretch = stronger contraction

   • Affected by duration of diastole (inversely related to heart rate)

   • Affected by venous return (directly proportional)

2. Contractility:

   • strength of contraction independent of pre/after load

   • how powerful the heart muscles are

   • affected by positive and negative inotropic agents, and medical conditions

3. Afterload:

   • pressure for ventricles to overcome to eject blood

   • resistance against which heart must pump

   • Determined by arterial pressure, systemic vascular resistance

   • blood vessel diameter plays a part

   • higher afterload = lower Stroke Volume

Regulators of Heart Rate

Neurohormonal Regulation (ANS + Hormones)

ANS:

• receptors send signals to cardiovascular center in medulla oblongata

• then signal travels to spinal cord

• reaches cardiac accelerator cells

• releases norepinephrine into SA/AV nodes

• increases heart rate

• or vagus nerve (cranial nerve X); acetylcholine activates M2 receptors decreasing heart rate

• Sympathetic = faster, stronger

• Parasympathetic = slower, weaker

Heart Failure

syndrome where heart can not pump enough blood

Complex syndrome: decreased CO → decreased oxygen supply to organs

Due to:

• Systolic Dysfunctions: ventricles can not pump

• Diastolic Dysfunctions: ventricles can not fill

Types:

HFrEF (reduced ejection fraction):

• Ejection Fraction <= 40%

• Systolic HF

• weakened heart muscle

HFpEF (preserved ejection fraction)

• Ejection Fraction >= 50%

• Diastolic HF

• stiffened heart muscle

Heart Failure Therapy

Comprehensive Therapy (four pillars of heart failure):

• ARNI

• Beta-Blockers

• MRA

• SGLT2

Conventional Therapy:

• ACE/ARB

• Beta-Blocker

Comprehensive Therapy has higher projected event free survival compared to Conventional