Cardiac Cell Refractoriness

• Cardiac cells possess general properties like refractoriness.

Refractoriness

• Represents the inability to elicit another action potential (AP) regardless of stimulus strength.
• Occurs for a period after a cardiac AP has been elicited.
• Gives rise to absolute/effective (ARP/ERP) and relative refractory periods (RRP).
• Prevents premature excitation and tetany.
• Recovery of excitability differs between fast and slow response cells.
  • Fast response means quicker recovery of excitability.
  • Slow response poses an increased risk of conduction block.

Refractory Periods in Ventricular Muscle Cells

• The absolute refractory period (ARP) spans from the start of phase 0 to the middle of phase 3 of the action potential.
• The relative refractory period (RRP) covers the remaining part of phase 3.
• Fast response action potentials have shorter refractory periods compared to slow response action potentials.

Cardiac Action Potentials (APs) and Refractoriness

• Fast response APs show rapid depolarization and repolarization, followed by a plateau phase.
• Slow response APs exhibit slower depolarization, repolarization, and a less defined plateau.

Refractory Period and Muscle Contraction in Ventricular Muscle Cells

• Rapid depolarization occurs due to opening of voltage-gated fast Na+ channels.
• A plateau (maintained depolarization) is due to opening of voltage-gated slow Ca2+ channels and closing of some K+ channels.
• Repolarization occurs due to opening of voltage-gated K+ channels and closing of Ca2+ channels.
• The refractory period occurs immediately before muscle contraction.

Automaticity

• Describes the ability of certain cardiac cells to spontaneously initiate/fire action potentials.
• Automatic and pacemaker activities are essentially the same.
• Normal cardiac automatic or pacemaker cells include the SA node, AV node, and specialized conducting tissue like the His-Purkinje system.
• Primary pacemakers differ from latent or subsidiary pacemakers.
• Automaticity relies on the If current and spontaneous phase 4 depolarization.
• Intrinsic and extrinsic factors control automaticity.

Autonomic Innervation of the Heart

• The heart is innervated by both sympathetic and parasympathetic nerve fibers.
• Sympathetic cardiac nerves originate from the sympathetic chain ganglion.
• Parasympathetic innervation arises from the vagus nerve.

Control of SA Nodal Pacemaker Activity and Heart Rate

• Sympathetic activity and epinephrine increase heart rate.
• Parasympathetic activity decreases heart rate.

Electrical Activity of the Heart

• The heart beats spontaneously and rhythmically throughout life.
• The spread of action potentials across muscle cell membranes triggers the heartbeat.
• Action potentials are cyclically initiated and conducted orderly through the heart via electrical or autorhythmic cells: SA node -> Atria -> AV node -> Bundle of His -> Purkinje fibers -> Ventricles.
• AV conduction delay allows ventricles to relax while the atria are contracting.

Electrocardiogram (ECG or EKG)

• Electrical currents generated during cardiac muscle depolarization and repolarization is measured by the ECG.
• Currents are conducted through body fluids and tissues surround the heart.
• The ECG detects the overall spread of electrical activity during depolarization and repolarization.
• Standard 12-lead ECG recordings use six limb leads (I-III, aVR, aVL, aVF) and six chest leads (V1-V6).

Normal ECG Waveforms

• A normal ECG has three distinct waveforms:
  • The P wave represents atrial depolarization.
  • The QRS complex represents ventricular depolarization.
  • The T wave represents ventricular repolarization.

ECG Waveforms and Their Correspondences to Electrical Status of the Heart

• TP interval is when the ventricles are relaxing and filling.
• The P wave represents atrial depolarization
• The PR segment represents AV nodal delay.
• The QRS complex represents ventricular depolarization when atria repolarize simultaneously.
• Time during which ventricles contract/empty is shown by the ST segment
• The T wave represents ventricular repolarization.
• After 200 msec SA node fires again.

Sequence of Cardiac Excitation and Associated ECG Waveforms

• Atrial excitation is shown by the SA node, followed by the AV node
• Ventricular excitation is shown by atrial relaxation, followed by complete ventricular excitation
• The ECG changes show this sequence.

Contractile Activity of the Heart

• Cardiac muscle fibers acting as the heart's functional unit, are interconnected into branching fibers.
• Adjacent cells connect end-to-end via intercalated discs
• Two types of membrane junctions are present within intercalated discs:
  • Desmosomes as cell-to-cell anchoring junctions.
  • Gap junctions as cell-to-cell communication junctions.
• Muscle mass forms a functional syncytium, causing it to get excited & contract as a single unit.

Types of Cardiac Muscle Structure

• Bundles of cardiac muscle are arranged spirally around the ventricle.
• Cardiac muscle fibers branch and interconnect via intercalated discs.
• Intercalated discs contain mechanically crucial desmosomes and electrically essential gap junctions.
• Cardiac autorhythmic cells rapidly spread depolarizations to contractile cells through their gap junctions.

Excitation-Contraction Coupling

• Action potential reaches cardiac cells.
• Calcium ions enter from the extracellular fluid (ECF) through L-type calcium channels.
• Entry induces calcium release from the sarcoplasmic reticulum into the cytosol.
• Troponin-tropomyosin complex in the thin filaments pulls aside, allowing myosin to bind.
• Cross-bridge cycling between thick/thin filaments occurs.
• Thin filaments slide inward between thick filaments. Contraction occurs.

The Cardiac Cycle

• Is a rhythmic pumping action triggered by excitation through the heart including - systole and diastole.

Systole

• Involves ventricular contraction and emptying, with two sub-phases: isovolumetric contraction and ejection periods.

Diastole

• Involves ventricular relaxation and filling, with two sub-phases: isovolumetric relaxation and filling periods.

Cardiac Cycle Phases

• Late diastole involves relaxed chambers and passively filled ventricles.
• Atrial systole forces a small addition of blood into ventricles.
• Isovolumetric ventricular contraction pushes AV valves closed but insufficient pressure to open semilunar valves.
• Ventricular ejection occurs ventricular pressure rises and exceeds pressure in arteries, causing semilunar valve opening, and blood ejection.
• Isovolumetric ventricular relaxation occurs as ventricles relax and pressure falls, blood flows back into cups of semilunar valves, snapping them shut.

Heart Sounds

• 1st heart sound (lub) is due to closure of AV valves at the start of ventricular contraction.
• 2nd heart sound (dub) is due to closure of aortic & pulmonary valves at the end of ventricular systole.
• 3rd heart sound is heard in early diastole, caused by inrush of blood during rapid ventricular filling.
• 4th heart sound (dub) heard immediately before the 1st sound (in late diastole) and is due to ventricular filling.

Blood Vessels

• Are also part of the Vascular System or Tree.
• The closed system directs flow of blood to organs and tissue.
• Blood vessels include:
  • Arteries to carry blood away from the heart to tissues.
  • Arterioles as smaller artery branches in organs.
  • Capillaries that facilitate exchange between blood / surrounding cells and smaller branches of arterioles.
  • Venules that are formed when capillaries rejoin and return blood to the heart.
  • Veins that are formed when veins rejoin and return blood to the heart.

Structure of Blood Vessels Walls

• Contain up to three 'tunics'.
  • The tunica externa (adventitia) forms the outer layer of connective tissue and elastin fibers.
  • The tunica media composes a middle layer of smooth muscle.
  • The tunica interna (intima) is the innermost layer. It consists of endothelial lining, basement membrane and layer of elastin

Arteries

• Serve as rapid transit to move blood from the heart.
• Main Types:
  • Elastic arteries such as aorta and pulmonary artery: Expand and recoil when ventricles relax due to layered elastin fibers
  • Muscular arteries such as the femoral & coronary: Consist of Thicker smooth muscle layer and are less elastic

Arterioles

• Smaller branches contain highest percentage of smooth muscle.
• They are major resistance vessels because they facilitate blood pressure drop for blood flow to organs.
• Consist of distribution cardiac output depending on body needs and can be regulated through blood pressure.
• Nervous and chemical mechanisms: Arterial tone is controlled through dilation and constriction.

Control of Tone in Arterioles

• Sympathetic neurons release norepinephrine.
• Sympathetic signals cause blood vessels to constrict, which increases signal rate.
• The release of norepinephrine causes blood vessels to dilate and decreases signal rate.

Chemical Controls of Arteriolar Tone

• Caused by:
  • Myogenic activity; oxygen and carbon dioxide levels
  • Endothelin.
  • Sympathetic stimulation
  • Angiotensin II and vasopressin.

Vasodilation

• Decreased contraction of circular smooth muscle in the arteriolar wall, as seen by:
  • Decreased release of the chemicals.
  • Nitric oxide
  • Histamine
  • Heat.

Capillaries

• Are smaller with dense branches that transfer nutrients and allow tissues to exchange.
• Materials exchange through diffusion, where materials move along a concentration gradient.
• Very thin walls consist of flat endothelial cell and a basement membrane.
• Water-filled pores let walls allow small substances through.
• Precapillary regulate blood.
• Three main types:
• Continuous - Narrow intercellular pores
• Fenestrated larger hole
• Discontinuous-very porous

Capillary Blood Flow

• Regulated by precapillary sphincters.
• If precapillary sphincters are contracted, this prevents blood flow.

Types of Capillaries

• The continuous contain continuous endothelial cells that are joined closely together and that narrow intercellular pores. Skeletal and cardiac muscles, lungs and adipose tissues are included.
• Fenestrated capillaries feature fenestrations (pores) plus narrow pores and these have greater permeability. These capillaries service the kidneys, endocrine glands and the intestines.
• Discontinuous sinusoidal capillaries include leaky capillaries and endothelial cells with very large intercellular pores. These capillaries serve the bone marrow, spleen and liver.

Exchange of Materials across Continuous Capillary Walls

• Includes interstitial fluid and endothelial cells.
• Lipid and water soluble substances pass through endothelial cells, plasma and small pores.

Capillary Exchange Mechanisms

• Mechanisms include the passage of solutes and fluids through diffusion, where solutes move along concentration gradients.
• Reabsorption and ultrafiltration of protein-free plasmas form Bulk Flow

Pressure

• Capillary Blood Pressure to form Inward pressure.
• Plasma-colloid osmotic pressure to form Inward pressure.
• Interstitial fluid hydrostatic pressure to form Outward pressure.
• Interstitial fluid colloid osmotic pressure to form Outward pressure.

Exchange of Solutes

• Occurs through passive diffusion with an exchange of carbon dioxide and glucose into the tissue.

Capillary exchange of fluid

• Includes filtration, absorption, and blood flow.

Veins and Venules

• Serve as the venous system that facilitates low resistance to send blood back to the heart.
• Veins and Venules comprise:
  • Venules
  • Smaller Veins
  • Large and Systemic Veins.
• Have low resistance to facilitate blood flow due to a large radius.
• Thin Walls with little muscle elastic recoil.
• One way valves and muscle pump facilitate blood flow.

Valves of the Veins

• Valves exist in the veins to prevent backflow of blood.
• When skeletal muscles compress veins, they force blood flow towards the heart using a “skeletal muscle pump”

Facilitation within Veins

• Cardiac output is facilitated in the bulk of venous return.
• End-diastolic volume is increased.
• Blood and venous volume is also augmented.

Pressures

• Systolic and diastolic pressure is affected by the large arteries.

Blood Vessel Characteristics

• Several hundred arteries are made of elastic tissue and large radius.
• Arterioles are highly enervated vessels of elastic tissue.
• Exchange of interstitial fluid and capillaries.
• Endothelium exists in the structure and basement membrane in venule valves and veins.

Cardiac Output(CO)

• Measures the heart's efficiency as a pump which include stroke and heart volume to increase blood flow.

Regulation

• Adjustments change SV & HR

• ANS controls the heart

• SNS increases HR

• PNS decreases HR

• Determinants of SV

• Preload

• Afterload

• Cardiac Contractility

Stroke Volume

• The heart changes contractility by the length of the muscle to contract and strengths of its EDV.
• [Ca++] creates cross-bridge formation which increases SV.
• The sympathetic system increases SV and contractility.

Blood Pressure

• Is mean arterial average that drives the flow in the tissue with: -Systolic BP -Diastolic BP -Pulse Pressure

Determinants of BP

• Cardiac Output
• Heart Rate -autonomic tone, catecholamines
• Stroke Volume - Cardiac contractility, venous return
• Total Peripheral Resistance -sympathetic tone
• -α1- & β2-adrenoceptors
• Circulating Hormones
• -Ang II, catecholamines
• Local Hormones
• • NO, ETSs, PGs, adenosine, etc.

Regulation of Blood Pressure

• It’s important to regulate and maintain balance to ensure proper BP.
• To prevent damage to heart as well short term and long-term control exists.
• Short Term - via baroreceptors
• Longterm - via the kidneys
• Short term consists of autonomic output affecting total heart functions.
• Long term includes how the kidneys adjust blood volume through salt and water balance