Circulatory 2

• The circulatory system is one of the normal systems of the body
• Lecture given by Dr G Boachie-Ansah

General Properties of Cardiac Cells

• Refractoriness refers to the heart's inability to elicit an action potential, regardless of stimulus strength
• Refractoriness occurs after a previously elicited cardiac action potential
• Refractoriness gives rise to absolute/effective (ARP/ERP) and relative refractory periods (RRP)
• The heart's refractoriness protects against premature excitation and tetany
• Recovery time of excitability differs in fast and slow response cells
• Fast response: Faster recovery of excitability
• Slow response: Slower recovery of excitability, increasing the risk of conduction block

Cardiac Action Potentials & Refractoriness

• Fast response = faster recovery of excitability
• Slow response = increased risk of conduction block due to slower recovery of excitability

Refractory Period & Muscle Contraction

• Rapid depolarization occurs due to opening of voltage-gated fast Na+ channels
• Plateau is maintained by opening voltage-gated slow Ca2+ channels and closing some K+ channels
• Repolarization occurs due to opening of voltage-gated K+ channels and closing of Ca2+ channels
• The refractory period is the time following stimulation during which a muscle cell is unresponsive.

Automaticity

• Automaticity is the ability of some cardiac cells to spontaneously initiate/fire action potentials
• Automatic cells are called cardiac automatic or pacemaker cells
• Normal cardiac automatic or pacemaker cells: SA node, AV node, and specialized conducting tissue (His-Purkinje system)
• Pacemakers can be primary, latent, or subsidiary
• Automaticity is based on If current and spontaneous phase 4 depolarization
• Automaticity has intrinsic and extrinsic controls

Autonomic Innervation of the Heart

• The autonomic nervous system innervates the heart through sympathetic and parasympathetic fibers
• The vagus nerve carries parasympathetic fibers from the dorsal motor nucleus of the vagus
• The medulla oblongata houses the cardioinhibitory center for parasympathetic control
• Sympathetic fibers originate from the thoracic spinal cord and sympathetic trunk
• Parasympathetic fibers slow heart rate, while sympathetic fibers increase heart rate and contractility

Control of SA Nodal Pacemaker Activity & Heart Rate

• Heart rate is controlled via the autonomic nervous system
• Parasympathetic activity decreases heart rate
• Sympathetic activity (and epinephrine) increases heart rate

Electrical Activity of the Heart

• The heart beats spontaneously and rhythmically throughout life
• Action potentials (electrical impulses) trigger muscle cell membrane spread
• Action potentials are cyclically initiated and conducted in an orderly sequence by electrical or autorhythmic cells The sequence: SA node → Atria → AV node → Bundle of His → Purkinje fibers → Ventricles
• AV conduction delay allows ventricles to be relaxed while atria are contracting

Electrocardiogram (ECG or EKG)

• Electrical currents generated by cardiac muscle during depolarization and repolarization
• The currents are conducted through body fluids and tissues around the heart and can be detected and recorded on the body surface
• The electrocardiogram (ECG or EKG) represents the summation of overall electrical activity during depolarization and repolarization
• Standard 12-lead ECG recording includes six limb leads (I-III, aVR, aVL, and aVF) and six chest leads (V1-V6)
• A normal ECG shows three distinct waveforms: P wave, QRS complex, and T wave
• P wave represents atrial depolarization.
• QRS complex represents ventricular depolarization.
• T wave represents ventricular repolarization.

Waveforms of the ECG

• The P-Q interval represents the time it takes for the cardiac impulse to travel from the atria to the ventricles
• The Q-T interval represents the time it takes for the ventricles to depolarize and repolarize.
• The S-T segment represents the period when the ventricles are contracting but not repolarizing.
• R represents ventricular depolarization.

Contractile Activity of the Heart

• Cardiac muscle fibers as the basic functional unit of the heart pump
• Individual cardiac muscle cells link together to form branching fibers
• Adjacent cells are joined end to end at specialized structures called intercalated discs
• The two types of membrane junctions within intercalated discs are:
• Desmosomes for cell-to-cell anchoring
• Gap junctions for cell-to-cell communication
• Muscle mass forms a functional syncytium, becoming excited and contracting as a single unit

Excitation Contraction Coupling

• An action potential enters from an adjacent cell
• Voltage-gated Ca2+ channels open allowing Ca2+ to enter the cell
• Ca2+ then induces Ca2+ release through ryanodine receptor-channels (RyR)
• Local release causes Ca2+ spark
• Summed Ca2+ sparks create a Ca2+ signal
• Ca2+ ions bind to troponin to initiate contraction
• Relaxation occurs when Ca2+ unbinds from troponin
• Ca2+ is pumped back into the sarcoplasmic reticulum for storage
• Ca2+ is exchanged with Na+. The Na+ gradient is maintained by the Na+-K+-ATPase

Cardiac Cycle

• The cardiac cycle involves a rhythmic pumping action triggered by excitation spreading through the heart
• There are two phases of the cardiac cycle
• Systole: Phase of ventricular contraction & emptying with isovolumetric contraction & ejection periods
• Diastole: Phase of ventricular relaxation & filling with isovolumetric relaxation & filling periods.

Heart Sounds

• 1st Heart Sound (lub): closure of AV valves at the start of ventricular contraction
• 2nd Heart Sound (dub): closure of aortic & pulmonary valves at the end of ventricular systole
• 3rd Heart Sound:
• Heard in early diastole
• Is due to inrush of blood during rapid ventricular filling
• 4th Heart Sound (dub):
• Heard immediately before the 1st sound (in late diastole)
• Is due to ventricular filling

Blood Vessels

• Blood vessels are also called the 'Vascular System or Tree'
• Blood vessels form a closed system
• They direct blood flow from the heart to organs and tissues, and back
• Blood vessels consist of:
• Arteries: Carry blood away from the heart to tissues
• Arterioles: Smaller branches of arteries within organs
• Capillaries: Facilitate exchanges between blood and surrounding cells
• Venules: Formed when capillaries rejoin and return blood to the heart
• Veins: Formed when venules rejoin and return blood to the heart

Structure of Blood Vessels

• Blood vessels are composed of up to 3 'tunics':
• Tunica externa (adventitia): Outer layer of connective tissue and elastin fibers
• Tunica media: Middle layer of smooth muscle
• Tunica interna (intima): Innermost lining of squamous endothelium with a basement membrane and elastin later

Arteries

• Arteries serve as rapid-transit conduits for blood from the heart to organs and act as pressure reservoirs providing driving force for blood during diastole
• The types are:
• Elastic Arteries (e.g., aorta & pulmonary artery): Numerous layers of elastin in vessel walls that expand when pressure rises and act as a recoil when ventricles relax
• Muscular Arteries (e.g., femoral & coronary arteries): Less elastic layer with a thicker layer of smooth muscle where diameter changes slightly as blood pressure rises and falls

Arterioles

• Arterioles are smaller branches of arteries within organs, containing the highest percentage of smooth muscle in their walls
• These are major resistance vessels
• Large pressure drops facilitate blood flow to organs via the network of vessels
• Vessel radius can be individually adjusted to distribute cardiac output (based on body's needs) and help regulate arterial blood pressure
• Arterioles contract or dilate via nervous and chemical mechanisms

Nervous & Chemical Control of Arteriolar Tone

• Normal arteriolar tone is the baseline level of constriction
• Vasoconstriction
• Increased contraction of circular smooth muscle in the arteriolar wall
• Increases resistance and decreases blood flow through the vessel
• It can be caused by: Increased myogenic activity or oxygen, decreased carbon dioxide, increased endothelin, or sympathetic stimulation
• Vasodilation:
• Decreased contraction of circular smooth muscle in the arteriolar wall,
• Decreases resistance and increased flow through the vessel
• It can be caused by: Decreased myogenic activity or oxygen, increased carbon dioxide, increased nitric oxide, or decreased sympathetic stimulation

Capillaries

• Capillaries are small and dense branches from arterioles and metarterioles within organs
• Nutrients and wastes are exchanged between blood and surrounding tissue cells
• Exchange occurs via diffusion
• Capillaries have very thin walls of one layer of flat endothelial cells and a thin basement membrane
• Walls are perforated by water-filled pores – permit passage of small, water-soluble substances
• Precapillary sphincters regulate blood flow
• The three main types of capillaries depend on the size of water-filled pores

Capillary Exchange

• Solute movement mostly results from passive diffusion
• Fluid movement results from bulk flow (ultrafiltration and reabsorption of protein-free plasma)
• The forces that effect fluid flow are: Capillary blood pressure (Pc), Plasma-colloid osmotic pressure (πp), Interstitial fluid hydrostatic pressure (PIF), and Interstitial fluid colloid osmotic pressure (πIF)
• Net exchange pressure = (Pc + πIF) - (πp + PIF) = (outward pressure) - (inward pressure)

Veins & Venules

• The venous system is low resistance
• Veins and venule returns blood from tissues to the heart
• The venous system comprises of:
• Venules
• Small veins
• Large systemic veins
• Systemic veins have large radius allowing low resistance to flow and allowing them to serve as blood reservoir/capacitance vessels
• Systemic veins have thin walls with little smooth muscle and elastin allowing high distensibility
• One-way valves and the ‘skeletal muscle pump’ ensure blood flows toward the heart

Factors That Facilitate Venous Return

• Cardiac Output
• Stroke Volume
• End-diastolic Volume
• Venous Valves

Regulation of Cardiac Output & Blood Pressure

• Efficiency and work of the heart is measured as Cardiac Output (CO)
• Cardiac Output = Volume of blood the heart pumps out each minute (ml/min or L/min)
• Cardiac Output is determined by:
• Stroke Volume (SV)
• Heart Rate (HR)
• CO = SV x HR
• Stroke volume (SV) = Volume of blood ejected by the left ventricle with each heart beat (ml/beat)
• Cardiac output is adjusted to meet physiological and metabolic needs via Stroke Volume (SV) and Heart Rate (HR)

Regulation of Cardiac Output

• The autonomic nervous system regulates heart rate
• Increased SNS (sympathetic tone) increases heart rate
• Increased PNS (parasympathetic tone) decreases heart rate
• Determinants of Stroke Volume (SV) are preload, afterload, and cardiac contractility

Factors Affecting Stroke Volume - Preload

• Preload is the end diastolic volume or pressure (EDV/P) before contraction begins
• EDV or EDP equals the volume of blood or amount of pressure in the ventricle before contracting (at the end of diastole)
• EDV ≃ Venous Return (VR)
• According to the Frank-Starling Law of the Heart, Stroke Volume (SV) is directly proportional to Preload (or VR)
• Increases in preload result in increased stretch of cardiac muscle fibers → increased SV

Factors Affecting Stroke Volume - Afterload

• Afterload is the "load" against which the heart must contract to eject blood into the aorta
• Equals the aortic pressure ≃ to systemic arterial BP
• Is determined by systemic or total peripheral resistance (TPR)
• SV is inversely proportional to afterload (or TPR)
• Increases in afterload results in decreased SV

Factors Affecting Stroke Volume - Contractility

• Contractility as heart's ability to change contraction force independent of resting muscle length
• Equals the strength of contraction at any given EDV
• It depends on the availability of intracellular Ca++ to participate in the contractile process
• SV is directly proportional to cardiac contractility
• Increased [Ca++]; → increased Actin-Myosin cross-bridge formation → increased Contractility → ↑sv
• Cardiac contractility is increased by SNS activation ⇒ ↑ SV

Regulation of Blood Pressure

• Systolic BP is the force exerted by blood on arterial walls during systole
• Diastolic BP is the force exerted by blood on arterial walls during diastole
• Pulse Pressure = Systolic BP – Diastolic BP
• Mean arterial BP is the average pressure responsible for driving blood forward into tissues
• Mean BP Formula: Diastolic BP + (1/3 x Pulse Pressure)

Regulation of Blood Pressure - Determinants

• Blood pressure is determined by: Cardiac output (CO) and total peripheral resistance (TPR)
• BP = CO x TPR.
• Factors determining cardiac output: Heart rate (autonomic tone, catecholamines) and stroke volume (cardiac contractility, venous return).
• Total peripheral resistance (TPR) relies on sympathetic tone, vasoconstrictor and vasodilation hormones, and local hormones

Mean Arterial Blood Pressure Regulation

• Mean Blood Pressure is kept in a narrow range to avoid problems
  • Must be high enough to ensure adequate perfusion in body and tissues
  • Can't be so high that it causes stress or potential damage from blood vessels
• Homeostatic Blood Pressure is controlled by:
  • Short-term control: via baroreceptors
  • Long-term control: via the kidneys

Regulations of Blood Pressure - Short Term Control

• Short-term adjustments happen within seconds
• Adjustments involve cardiac output & peripheral resistance
• The autonomic nervous system influences the rate adjustments for the heart, arterioles and veins

Regulations of Blood Pressure - Long Term Control

• Long-term adjustments happen over longer periods of time, (minutes to days)
• Adjustments involve normal salt and water balance, influencing the blood volume