12 Cardiac Pathophysiology

What determines blood pressure?

• Cardiac output

• Vascular

• Blood volume

• Regulation by CNS and Endocrine systems

What is the function of the heart?

• Pump blood, creating hydrostatic pressure to perfuse the body

• Endocrine organ: secretes Atrial Natriuretic Peptide (causes kidney to add salt into urine to decrease BP and is a vasodilator)

How does the heart affect blood pressure?

By increasing cardiac output, the heart can increase blood pressure. To decrease BP, the heart decreases its output.

What is the path blood travels through the cardiovascular system starting at the vena cava?

Vena Cava → Right atrium → Tricuspid valve → right ventricle→ pulmonic valve → pulmonary artery → pulmonary arterioles → pulmonary capillaries → pulmonary venules → pulmonary vein → Left atrium → mitral valve (bicuspid) → left ventricle → aortic valve → aorta → systemic arteries → systemic arterioles → systemic capillaries → systemic venules → systemic veins

What is the purpose of the valves?

To produce a one-way blood flow and slow electrical conduction to allow proper ventricular filling.

How does valve create a one-way blood flow?

• Leaflets open and close based on pressure

• Papillary muscles contract with the chamber to prevent prolapse and regurgitation

What are the valves made up of?

Connective tissue, they are a part of the fibrous skeleton

Where are the papillary muscles connected to?

The valve flaps and the heart muscles to prevent valve inversion. It is connected to the valve leaflets by chordae tendinae.

What are the layers of the heart?

• Endocardium: continuous with endothelium

• Myocardium: pacemaker cells and cardiac myocytes

• Pericardium or pericardial sac

  • Visceral pericardium: contains coronary arteries and veins

  • Parietal pericardium

What are the functions of pacemaker cells?

• Set heart rate = chronotropy

• Exhibit automaticity, bringing themselves to threshold via voltage-gated channels

How are pacemaker cells organized?

• Sinoatrial nodes (SA) around the atriums with 100 betas/min; With vagal brake = 70 bpm

• Atrioventricular node (AV): 40 bpm

• Bundle of His: Transmits electrical impulses from AV to ventricles

• Purkinje Fibers: ensure the ventricles contract simultaneously

How does the impulse propagate?

• SA nodes causes atrial myocyte depolarization and contraction

• AV delay, slowing conduction of AP through node allows the ventricles to fill

• Bundle of His and Purkinje fibers cause depolarization of ventricles and contraction

What are the phases of an AP of pacemaker cells?

1. Pacemaker potential brings cell to threshold: funny channels = Na influx = funny current; transient calcium channel opens at end = Ca influx

2. Depolarization phase from DHPR channels/L-Type Ca Channels = Ca influx

3. Repolarization Phase from K Channels = K efflux

4. Immediately begins pacemaker potential: no static rest

How are pacemakers regulated?

• ANS regulates HR/chronotropy

  • SA and AV nodes under reciprocal control:

    • SNS = B1 adrenergic receptors: Increases effect/HR

    • PNS = M2 receptors: Decreases effect/HR

How can chronotropy be increased/positive chronotropy?

• B1 stimulation by SNS/agonist

• M2 blocker

• Thyroid= High T3/T4 causes increase in B1 receptors

How can chronotropy be decreased/negative chronotropy?

• B1 Antagonist/blocker

• M2 Agonists

• T3/T4 is low, causing a reduction in B1 receptors

What are some Rx to change chronotropy?

• Positive Chronotropic Agents

  • Beta1 agonists

  • M2 antagonists (anticholergics): Atropine (causes mydriatic iris)

  • Synthroid

• Negative Chronotropic Agents

  • Beta1 antagonists: metoprolol (Lopressor)

  • M2 agonists

  • CCB/Non-DHPR Blockers: Phenylalkylamine (Verapamil) for cardiac specific; Benzothiazepine (Diltiazem) for cardiac and vascular

  • Other: Cardiac Glycosides to increase vagal stimulation: Digoxin and Ouabain

What are the differences between skeletal fibers and cardiac myocytes?

Cardiac myocytes are mononucleated, branched with intercalated discs full of gap junctions for electrical synapses, and regulated by the SNS

How does the SNS affect the cardiac muscles?

An increase in SNS innervation causes an increase in contraction force. A decrease in SNS innervation causes a decrease in contraction force.

What does the cardiac myocytes excitation-contraction coupling include?

And action potential and twitch.

What are the phases of an AP of a cardiac myocyte?

• Phase 0: Depolarization; Na channels open

• Phase 1: Slight repolarization: Na channels close, transient K channels open

• Phase 2: Plateau: transient K channels open and L-type Ca channels open (DHPR)

• Phase 3: Repolarization: L-type Ca channels close (DHPR) and K channels open

• Phase 4: Reset

What are the steps of a cardiac myocyte contraction?

1. Depolarization by pacemaker or adjacent myocytes

2. AP begins: voltage-gated DHPR channels open, Ca influx

3. Ca from ECF binds to RyR and opens it

4. Ca released from SR (CICR = Ca induced Ca release) = spark [most important source]

5. Ca binds troponin, myosin heads crossbridge and contraction occurs

6. Repolarization of AP: all voltage-gated channels reset

How is Ca removed from the ICF?

• SERCA pumps Ca into SR for the spark in the next contraction

• Pump Ca into ECF via NKA (Sodium Potassium ATPase) or CNE (calcium sodium exchanger)

Why is the refractory period important in cardiac muscle?

It prevents tetany (sustained contraction) by ensuring that each contraction is followed by full relaxation before another AP occurs.

How are AP and twitch linked in cardiac myocytes?

The calcium used in the action potential is also involved in the muscle twitch for contraction.

Why is there no tetany in cardiac muscle?

The refractory period lasts almost as long as the contraction, preventing repeated stimulation before relaxation occurs. AKA, no latent period for build up of AP to increase contraction force.

What mechanisms regulate contraction strength?

• Inotropy: regulation of calcium in ICF

• Preload: length-tension relationship

What affects the cardiac myocytes contraction strength?

The strength of contraction is based on Ca2+ in the cell

What do positive inotropic agents do?

The increase Calcium in the cell to make a stronger contraction.

What do negative inotropic agents do?

Decrease Ca in the cell to make a weaker contraction

What are some positive ionotropy?

• Beta 1 agonists=- decease heart size and heart rate

• increase thyroid = increase number of Beta1 receptors

What are some negative ionotropy?

• Beta1 blocker

• Decrease thyroid = decrease number of beta1 receptors

What is the difference between chronotropy and inotropy?

Chronotropy is heart rate, inotropy is contraction strength

What does high SNS do to inotropy/contractility?

High SNS stimulates inotropy by enhancing intracellular Ca²⁺ levels.

• Epinephrine (Epi) and Norepinephrine (Norepi) bind to β₁-adrenergic receptors.

• This leads to phosphorylation of:

  • DHPR (L-type Ca²⁺ channels): Increases Ca²⁺ influx.

  • RyR2 (Ryanodine Receptors): Enhances Ca²⁺ release from the SR.

  • SERCA (SR Ca²⁺-ATPase): Increases Ca²⁺ reuptake, leading to stronger and faster contractions.

What does low SNS do to inotropy/contractility?

Low SNS inhibits inotropy by decreasing the amount of calcium in the cell.

What are some drugs that inhibits inotorpy?

• Beta1 antagonists: Metoprolol or lopressor

• Calcium-channel blockers/cardioinhibitory

  • Benzothiazepine: Diltiazem

  • Phenylalkylamine: Verapamil (cardiac-specific)

What are cardiac glycosides?

A class of drugs that increase cardiac contracility (positive inotropy) and decreases the heart rate (negative chronotropy) to cause an overall increase in CO. It is cardiostimulatory

What is preload?

The volume of blood loaded into the heart before ventricular contraction

What are the other names for preload?

• Venous return

• End-diastolic volume

• Frank-Starling Law of the Heart

How does the volume of blood filling the heart affect contraction strength?

Sarcomeres are stretched as the heart fills with blood. The changes in the length of sarcomeres will determine the strength of heart contraction.

How can the sarcomere determine the amount of stretching/changes in length it experiences?

The amount of myosin-actin overlap

What is the relationship between length and tension?

Linear. Lower preload/length = lower tension. Higher preload = higher tension

What things can affect preload?

• Venoconstriction by SNS

• Muscle pump: veins between skeletal muscles pump blood toward heart

• Respiratory pump: during inspiration, throacic pressure drops, drawing blood into the heart

What is Systole?

Isovolumetric contraction and ejection of blood

What is diastole?

Isovolumetric relaxation, with active and passive ventricular filling

Starting at last diastole, what are the phases of the cardiac cycle?

• Late diastole: Passive filling as atrioventricular valves are open semilunar valves closed

• Atrial systole (diastole): Atria depolarize and contract to actively fill the ventricles through the atrioventricular valves

• Isovolumetric contraction (Systole): Ventricles depolarize and start to contract. All valves are closed and pressure is building up [First heart beat sound]

• Ejection (Systole): BLood ejected into aorta and pulmonary artery as semilunar valves open and atrioventricular valves remain closed

• Isovolumetric relaxation (diastole): ventricular repolarization as all valves close. No bloove movement and pressure drops [second heart beat sound]

How is cardiac output measured?

In liters per minute. Typically rate is 5L/minute

How to cardiac output change?

Change stroke volume and/or heart rate.

What determines Cardiac output?

Chronotropy/Heart Rate: activity of pacemaker cells and chronotropic agents

Stroke Volume: Due to inotropy/contractility, preload, and afterload

What is afterload?

resistance to ejection caused by:

• hypertension

• Valve disease