Circulatory and Respiratory System

Cardiac Cycle

• Definition:
  • All mechanical events during a complete heartbeat, from its generation to the beginning of the next.
  • Alternates between systole (contraction) and diastole (relaxation).
  • Observe pressure and volume changes in chambers during the cycle.
  • One full cardiac cycle equals one heartbeat.
  • Includes systole and diastole of both atria and ventricles.
  • Example: At 75 bpm, one cardiac cycle requires 0.8 seconds.

Cardiovascular Terminology

• Must-know terms:
  • Systole: Contraction phase of the heart.
  • Diastole: Relaxation phase of the heart.
  • Heart Rate (HR): Beats per minute (bpm).
  • Stroke Volume (SV): Volume of blood ejected per beat.
  • Cardiac Output (Q): Volume of blood ejected per minute.
  • Venous Return: Rate of blood flow back to the heart.
  • End-Diastolic Volume (EDV): Volume of blood in ventricles at the end of diastole.
  • End-Systolic Volume (ESV): Volume of blood in ventricles at the end of systole.
  • Ejection Fraction (EF): Percentage of EDV ejected per beat.
  • Preload: Volume entering ventricles.
  • Afterload: Resistance the left ventricle must overcome to circulate blood.
  • Total Peripheral Resistance (TPR): Resistance to blood flow in systemic circulation.
  • Mean Arterial Blood Pressure (MAP): Average arterial pressure.

Relationships Between Cardiovascular Variables

• SV, EDV, and ESV:
  • SV = EDV – ESV
  • ESV = EDV - SV
• Q, HR, and SV:
  • Q = HR * SV
• EF, SV, and EDV:
  • EF = SV/EDV
  • EF = (EDV – ESV)/EDV
• MAP, Q, and TPR:
  • MAP = Q * TPR
  • MAP = (HR * SV) * TPR

New Cardiovascular Terminology

• Chronotropic (chronotropy):
  • Refers to the rate of contraction.
  • Changes heart rate (positive or negative).
  • Example: Beta-blockers are negative chronotropes.
• Inotropic (inotropy):
  • Refers to the force of contraction (myocardial contractility).
  • Changes the force of heart contraction (positive or negative).
  • Example: Digoxin is a positive inotrope.
• Dromotropic (dromotropy):
  • Refers to the speed of conduction through the heart’s electrical conduction system.
  • Changes the speed of action potential conduction (positive or negative).
  • Example: Calcium channel blockers are negative dromotropes.

Factors Affecting Myocardial Performance

• Preload: Volume entering ventricles.
• Afterload: Resistance left ventricle must overcome to circulate blood.
• Inotropic State: Strength of contraction.

Preload

• "Capacity" of ventricles to stretch at the end of diastole.
• Initial length to which myocardial muscle is stretched prior to contraction.
• Cardiac preload is proportional to the amount of filling the heart experiences during diastole.
• Greater preload leads to greater EDV.
• Increased filling increases the potential isometric contractile force that can be generated.
• Greater preload -> greater EDV -> greater myocardial force generation -> greater SV.

Frank-Starling Mechanism

• Describes the heart’s ability to change its force of contraction (and therefore stroke volume) in response to changes in LV filling.

• As EDV increases, the LV myocardium stretches, yielding an increase in stroke volume and contractile force.

• Increased preload increases active tension developed in cardiac muscle fibers.

• Increased preload increases the velocity of cardiac muscle fiber shortening at a given afterload and inotropic state.

Factors that Increase Cardiac Preload

• Increased ventricular filling (increased EDV, increased preload).
• Increased total blood volume.
• Standing to supine body position.
• Increased contraction of respiratory, abdominal, or limb muscles.
• SNS activation of smooth muscle in smaller veins.
• Increased atrial contractility.
• Decreased HR.

Factors that Decrease Cardiac Preload

• Decreased ventricular filling (decreased EDV, decreased preload).
• Decreased ventricular compliance.
• Impaired atrial contraction.
• Supine to standing body position.
• Valsalva maneuver.
• Decreased blood volume.
• Increased HR.

Afterload

• Resistance to ventricular ejection.
• Forces against which cardiac muscle must work to generate pressure and shorten during contraction.
• Factors that increase afterload:
  • Increased aortic pressure.
  • Increased total peripheral resistance (systemic vascular resistance).
  • Aortic valve stenosis.
• Increased afterload leads to increased ESV and decreased SV.

Increased Afterload Decreases Stroke Volume

• Increased afterload alters the force-velocity relationship of cardiac muscle.
• Leads to a decreased velocity of shortening of cardiac muscle fibers.
• Reduces the rate of ejection, so more blood is left in the LV at the end of systole.
• Result: increased ESV, therefore decreased SV.

Inotropic State

• Inotropic stimuli shift the isometric length-tension curve.
  • Positive inotropes shift the curve to the left, enabling cardiac muscle to generate more force at any given preload.
• Inotropic stimuli shift the force-velocity curve.
  • Positive inotropes shift the curve upwards, increasing the velocity of shortening at a given afterload.
• Major factors affecting inotropic state:
  • SNS activation and catecholamines (positive inotropes).
  • PNS activation (negative inotrope).

Increased Inotropic State Increases Stroke Volume

• Increased inotropic state enables cardiac muscle to generate more isometric tension and increase velocity of shortening.
• Increased force generation and rate of ejection, thus less blood is left in the LV at the end of systole.
• Result: decreased ESV, and therefore increased SV.

Over-Arching Take-Aways

• Factors that tend to increase myocardial performance:
  • Increased preload (but places increased stress on a failing heart).
  • Decreased afterload.
  • Increased inotropic state.
• Factors that tend to decrease myocardial performance:
  • Decreased preload (eases stress on a failing heart).
  • Increased afterload.
  • Decreased inotropic state.

Quantification of Blood Pressure (BP)

• Systolic BP (SBP): Pressure in arteries during ventricular systole.
• Diastolic BP (DBP): Pressure in arteries during ventricular diastole.
• Pulse pressure = SBP – DBP
  • Provides information about vascular health.
  • High pulse pressures can be a strong indicator of heart attacks in older adults.
  • May indicate vascular stiffness or damage due to atherosclerosis.

Mean Arterial Pressure (MAP)

• Weighted average of SBP and DBP.
• Affected by cardiac output and total peripheral resistance.
• Important clinical measure in critical care.
• Normal MAP = 70-110 mmHg
  • MAP = DBP + (0.33 * [SBP - DBP])
  • MAP = Q * TPR

Orthostatic Hypotension

• Drop in BP that accompanies the change from supine to standing.
• Assessment:
  • Initial BP and HR assessment when patient is supine and at rest for ≥ 25 minutes.
  • Patient moves to standing position.
  • Repeat BP and HR assessment immediately and again at 3 minutes.
  • Patient is orthostatic if SBP drops > 20 mmHg or if DBP drops > 10 mmHg.
• Common symptoms: lightheadedness, dizziness, loss of balance, leg weakness.

Physiological Factors that Alter MAP

• MAP = Q * TPR
• Q = HR * SV
• Factors that alter HR and/or SV also alter MAP.
• Total Peripheral Resistance (TPR) is the resistance to blood flow offered by all of the systemic vasculature (AKA systemic vascular resistance).
• Factors that alter TPR also alter MAP.
• Must consider the relative contribution of each factor in order to determine net effect on MAP

Factors that Alter Cardiac Output (Q)

• Increased PNS tone: decreases HR and SV.
• Increased SNS tone: increases HR and SV.
• Increased EPI & NE concentrations: increases HR and SV.
• Increased renin-angiotensin-aldosterone pathway activity: increases SV (increases plasma volume).
• Increased anti-diuretic hormone (ADH) concentration: increases SV (increases plasma volume).
• Increased atrial natriuretic peptide (ANP) concentration: decreases SV (opposes the renin-angiotensin-aldosterone pathway).

Summary of Factors that Increase Q

• Increased SNS activity: increases HR and SV.
• Increased EPI & NE concentrations: increase HR and SV.
• Increased renin-angiotensin-aldosterone pathway activity, ADH concentration, and respiratory & skeletal muscle pump activity: increase SV.

Summary of Factors that Decrease Q

• Increased PNS activity: decreases HR and SV.
• Increased ANP concentration: decreases SV (decreases cardiac preload).
• Increased TPR: decreases SV (increases cardiac afterload).
• Since MAP = Q * TPR, factors that increase Q tend to increase MAP, and factors that decrease Q tend to decrease MAP.

Factors that Alter Total Peripheral Resistance (TPR)

• Increased SNS tone: increases TPR (vasoconstriction).
• Increased EPI & NE concentrations: increase or decrease TPR (vasoconstriction or vasodilation).
• Increased Angiotensin II concentration: increases TPR (vasoconstriction).

Summary of Factors that Increase TPR

• Increased SNS activity, catecholamine, angiotensin II, and ADH concentrations: vasoconstriction in some tissues.
• Increased total vessel length.
• Increased blood viscosity.

Summary of Factors that Decrease TPR

• Increased plasma ANP concentration: vasodilation.
• Increased catecholamine concentrations: vasodilation in some tissues.
• Since MAP = Q * TPR, factors that increase TPR will tend to increase MAP, and factors that decrease TPR will tend to decrease MAP.
  *Autoregulatory mechanisms can act as vasoconstrictors or vasodilators

Anti-Hypertensive Medication Overview

• Beta Blocker:
  • Decreases stimulation of beta-adrenergic receptors in the heart and blood vessels.
  • Result: Decreased HR and SV.
  • Result: Vasodilation.
• Calcium channel blocker:
  • Decreases intracellular calcium in the heart and blood vessels.
  • Result: Decreased HR and SV.
  • Result: Vasodilation.
• Angiotensin Converting Enzyme (ACE) inhibitor:
  • Decreases conversion of angiotensin I -> angiotensin II.
  • Result: Decreased production of aldosterone.
  • Result: Increased urinary excretion of sodium and water.
  • Result: Vasodilation.
• Diuretic:
  • Increases urine output.
  • Result: Decreased Q.
• Angiotensin II Receptor Blocker (ARB):
  • Decreases receptor binding of angiotensin II.
  • Result: Decreased stimulation of aldosterone secretion.
  • Result: Increased urinary excretion of sodium and water.
  • Result: Vasodilation.
• Renin Inhibitor:
  • Inhibits the binding of renin to angiotensinogen.
  • Result: Decreased production of angiotensin II and stimulation of aldosterone secretion.
  • Result: Increased urinary excretion of sodium and water.
  • Result: Vasodilation.

General Mechanism of Action (Baroreceptors)

• Baroreceptors sense the degree of stretch in vessels.
• Decreased BP = decreased stretch.
• Increased BP = increased stretch.
• The degree of stretch affects the rate that nerve impulses are sent to the CV center in the medulla oblongata.
• Decreased stretch results in a slower conduction of nerve impulses to the CV center.
• Increased stretch results in a faster conduction of nerve impulses to the CV center.

Lymphatic System

• Network of lymph, lymph vessels, lymph nodes, and lymphatic organs.
• One-way transport system for fluid, proteins, and other substances.
• Collects fluid from the interstitium and returns it to the bloodstream. Major functions:
  • Regulation of tissue fluid balance.
  • Transport route for immune cells, tumor cells, hormones, nutrients, waste products, proteins, and other molecules.
  • Lipid absorption and transport from the gastric system.
  • Removal of cellular debris.
  • Reservoir for proliferating white blood cells and tumor cells (lymph nodes).

Lymphatic System Structures and Components

• Lymph.
• Lymph vessels.
• Lymph nodes.
• Lymphatic organs/tissues (e.g. spleen, thymus, tonsils & adenoid, bone marrow).

Edema

• An abnormal increase in interstitial fluid if net filtration exceeds net reabsorption.
• Example: Result of excess fluid filtration:
  • Increased capillary permeability due to injury or inflammation (i.e. burns, allergic reactions, etc.).
  • Fluid buildup due to an obstruction such as a clot.
  • Fluid buildup due to a weakened heart (i.e., congestive heart failure).
  • Fluid buildup due to increased blood volume during pregnancy.
• Example: Result of inadequate fluid reabsorption:
  • Decreased concentration of plasma proteins lowers BCOP.
• Example: Result of decreased removal of excess filtrate by the lymphatic system:
  • Fibrosis and scarring of lymph nodes and lymphatic vessels.

Ascites

• Edema in the peritoneal cavity of the abdomen.
• Most commonly seen in individuals with cirrhosis of the liver.
• Increased pressure in the hepatic portal vein due to cirrhosis leads to fluid leakage out of the vasculature.
• Fluid leakage out of the vasculature due to inflammation.

Lymphedema

• Progressive swelling that occurs when protein-rich fluid accumulates in the interstitium.
• Primary lymphedema:
  • Genetic and familial abnormalities in lymphatic structures or function.
• Secondary (acquired) lymphedema:
  • Secondary to damage of lymphatic structures.

Anatomy of the Lungs

• The right lung has 3 lobes.
• The left lung has 2 lobes.
• Lobes consist of segments.
• Each lung has 10 segments.
• Each segment is supplied by its own tertiary bronchus and branch of the pulmonary artery.
• Each segment is innervated by the ANS.

The Pleurae

• Membranous Serous Sac.
• Visceral Pleura:
  • Covers the surface of each lung.
  • Inseparable from the tissue of the lung.
  • Adheres to all surfaces of the lung.
• Parietal Pleura:
  • Inner surface of the chest wall, diaphragm, and mediastinum.
• Pleural Space.
• Pleurisy: inflammation of the pleurae
  • Occurs when an infection or damaging agent irritates the pleural surface.
  • Sharp chest pains are the primary symptom of pleurisy.

Referred Pain Patterns

• Costal and peripheral diaphragmatic pleura refer pain to the thoracic and abdominal walls.
• Mediastinal and central diaphragmatic pleura refer pain to the lower neck and shoulder.
• Visceral pleura is sensitive to stretch but is insensitive to common sensations such as pain and touch. It receives an autonomic nerve supply from the pulmonary plexus.

Muscles of Pulmonary Ventilation

• Primary muscles for quiet inspiration:
  • Diaphragm: Primarily innervated by the phrenic nerve (C3-C5).
  • External intercostals: Primarily innervated by intercostal nerves (T1-T11).
• Accessory muscles during forced inspiration:
  • Sternocleidomastoid, scalenes, trapezius, pectoralis major and minor, serratus anterior, latissimus dorsi.
• Inspiration is an active process.
• Quiet expiration is a passive process:
  • No active muscle action.
  • Due to elastic recoil and changes in alveolar surface tension.
• Forced expiration is an active process:
  • Due to disease, increased exertion.
  • Primary muscles: internal intercostals, external and internal obliques, rectus abdominus.

Alveolar Surface Tension

• An expression of intermolecular attraction at the surface of a liquid.
• In the alveoli, water molecules in the thin layer of fluid in alveoli are strongly attracted to each other.
• Causes alveoli to want to collapse; needs to be overcome for inhalation.
• Relationship between surface tension (T), Pressure due to surface tension (P), and alveolar radius (r):
  • (Pressure * radius) is proportional to tension.
  • Pressure and radius are inversely proportional to each other.
  • When alveolar radius decreases, then a larger pressure must be produced in order to overcome tension in the alveolus and keep it from collapsing.
  • Question: when during ventilation is alveolar radius at its smallest?
  • (P*r) \alpha T
  • P \alpha (T/r)

Role of Surfactant

• Detergent-like substance produced by type II alveolar cells.
• Lowers alveolar surface tension and prevents alveoli from collapsing.
• Makes it easier for the lungs to expand (i.e., increases lung compliance).

Pulmonary Compliance

• How easily the lungs and chest wall can expand or contract.
• Depends upon the elasticity of the lungs and surface tension of alveoli.
• Some diseases decrease compliance (i.e., the lungs become stiffer):
  • Examples: scar tissue, pulmonary edema, reduced surfactant.
  • More work is required to inflate the lungs to bring in a normal tidal volume.
• Some diseases increase compliance:
  • Example: for individuals with emphysema, lungs have become overstretched from chronic coughing and congested airways.
  • Lungs are very distensible and easy to inflate.
  • However, elastic recoil is reduced and so additional effort is required to force air out of the lungs.

Airway Resistance

• Airflow = (P1 – P2) / Resistance
• P1 – P2 is the pressure difference at the two ends of the airway.
• The most important variable that contributes to airway resistance is the diameter of the airway (sound familiar?).
• Inverse relationship between airway diameter and airway resistance.
• Consider asthma.

Lung Volumes and Capacities

• Inspiratory Capacity (IC): maximal volume of air that can be inhaled.
• Functional Residual Capacity (FRC): volume of air left in the lungs at the end of normal exhalation.
• Vital Capacity (VC): volume of air that can be forced out of the lungs following a maximal inhalation.
• Total Lung Capacity (TLC): total volume of air that can be contained in the lungs.

Forced Expiratory Volumes

• Forced expiratory volume (FEV1): the maximum volume of air forcibly exhaled in 1 second.
• Forced expired volume / forced vital capacity ratio (FEV1/FVC): percentage of FVC forcibly exhaled in 1 second.
• Forced expiratory flow (FEF25-75): maximum mid-expiratory flow rate, measured by drawing a line between points representing 25% and 75% of FVC.

Obstructive Pulmonary Disease

• Airflow is impeded during expiration.
• Obstruction of the small airways, which compromises airflow out of the lungs.
• Abnormally high amount of air is left in the lungs at the end-expiration.
• Major examples: COPD, asthma, cystic fibrosis, bronchiectasis.

Restrictive Pulmonary Disease

• Lungs cannot fully expand during inspiration.
• Lung and/or chest wall stiffness, nerve and/or muscular damage, muscular weakness.
• Some primary causes: pulmonary fibrosis, tuberculosis, respiratory distress syndrome.
• Some secondary causes: certain neuromuscular diseases (e.g., myasthenia gravis, muscular dystrophy, ALS), obesity, ascites, diaphragmatic hernia.

Effects on Pulmonary Compliance (Obstructive vs. Restrictive)

• Obstructive Disease
  • Generally increased; magnitude depends on the specific disease.
  • Explanation: Lungs have become overstretched from chronic coughing and congested airways, so lungs are very distensible and easy to inflate.
  • However, elastic recoil is reduced, and so additional effort is required to force air out of the lungs.
• Restrictive Disease
  • Generally decreased; magnitude depends on the specific disease.
  • Explanations:
    • Decreased elasticity of the lungs (e.g., from the formation of scar tissue).
    • Decreased surfactant in the alveoli.
    • Decreased ability for the chest wall to move.
    • Muscular weakness
    • Nerve and/or muscular damage

Effects on Pulmonary Resistance (Obstructive vs. Restrictive)

• Obstructive Disease
  • Generally increased; magnitude depends on the specific disease.
  • Explanations:
    • Excessive narrowing of airways due to inflammation.
    • Thickened airway epithelium.
    • Smooth muscle spasm.
    • Increased mucus.
• Restrictive Disease:
  • Generally unchanged.
• Altogether, obstructive pulmonary disease is marked by decreased airflow upon forced expiration, while restrictive pulmonary disease is marked by a reduction in lung volume.

Major Ventilatory Impairments Associated with Obstructive Disease

• Increased energy expenditure is devoted to breathing.
  • Expiratory muscles must do additional work in order to overcome increased airway resistance.
• Hyperinflation of lungs places inspiratory muscles at a mechanical disadvantage.
• Increased dead space contributes to an inappropriately high ratio between physiological dead space and tidal volume.
• Increase in “wasted ventilation.”

"Barrel Chest" Appearance

• Particularly associated with emphysema.
• Lungs are persistently over-inflated with air.
• Trapped air and alveolar distension change the size and shape of the chest.

Major Ventilatory Impairments associated with Restrictive Disease

• Increased energy expenditure is devoted to breathing.
  • Inspiratory muscles must do additional work in order to overcome decreased pulmonary and/or thoracic compliance.
• Ventilatory muscle strength may be reduced.
• The decreased amount of air is able to get into and out of the lungs.

Muscular Atrophy and Dysfunction Associated with Pulmonary Disease

• Lower limb muscles (e.g., quadriceps) are particularly affected in patients with COPD.
• Fiber type shift from Type I -> Type II.
• Atrophied Type II fibers.
• Exacerbated by aging, nutritional abnormalities, and systemic corticosteroid treatment.
• Structural abnormalities include damage to sarcolemma, mitochondria, sarcomeres, and sarcoplasmic reticulum.

Other Physiological Impairments Associated with Pulmonary Disease

• Decreased lactate threshold leading to increases in ventilatory demand and shortness of breath
• Pulmonary hypertension:
  • Secondary to chronic hypoxemia or restriction of the pulmonary vascular bed.
• Right ventricular dysfunction.
• Cyanosis - low blood oxygen levels and poor oxygen delivery to tissues
• Polycythemia due to low blood oxygen levels
• Increased WBC counts and inflammatory biomarkers due to irritation of cigarette smoke
• Systemic inflammation associated with COPD pathogenesis
• Susceptibility to infections -> poor secretion clearance
• Increased fear of dyspnea

Additional Considerations in Pulmonary Impairment

• Higher prevalence of anxiety and depression compared to the general public.
• Coughing, shortness of breath, and fatigue, particularly upon exertion.
• Symptoms may keep patients awake at night -> increased fatigue during the day.

Gas Exchange in the Pulmonary and Systemic Circulations

• External respiration:
  • Pulmonary gas exchange.
• Internal respiration:
  • Systemic gas exchange.
• O2 and CO2 move between lungs, circulation, and body tissues according to individual partial pressure gradients.

Major Factors Affecting the Rate of Gas Diffusion

• Partial pressure of gases in the atmosphere:
  • Increased pO2 increases the diffusion rate of O2 from inspired air to alveoli to pulmonary circulation.
  • Atmospheric pO2 decreases as altitude above sea level increases.
• Surface area available for diffusion:
  • Large surface area of our alveoli increases diffusion rate.
  • Consider consequences of alveolar/pulmonary capillary membrane destruction, or decreased ability to expand lung parenchyma.
• Distance over which diffusion occurs:
  • Small diffusion distance (thin membranes) increases diffusion rate.
  • Consider consequences of pulmonary edema and pulmonary fibrosis.
• Molecular weight and solubility of gases:
  • Lower molecular weight increases diffusion.
  • O2 has a lower molecular weight than CO2.
  • Increased solubility increases diffusion.
  • CO2 is ~24x more soluble than O2.
  • Net outward CO2 diffusion occurs more rapidly than net inward O2 diffusion.

Transport of Oxygen in the Blood

• Modes of transportation:
  • Dissolved in Plasma = ~1.5%.
  • Bound to hemoglobin (HbO2) = ~98.5%.

Transport of Carbon Dioxide in the Blood

• Modes of transportation:
  • Dissolved in plasma= ~9%.
  • Bound to hemoglobin (HbCO2)= ~13%.
  • Bicarbonate ions (HCO3 -)= ~78%.

Oxygen-Hemoglobin Dissociation Curve

• High pO2 facilitates loading of O2 onto Hb in RBCs.
  • Occurs in pulmonary capillaries.
  • At the right part of the curve, large changes in pO2 yield small changes in %HbO2 saturation.
• Low pO2 facilitates unloading of O2 to tissues.
  • Occurs in systemic tissue capillaries, particularly exercising muscles.
  • At the left part of the curve, small changes in pO2 yield large changes in %HbO2 saturation.

Effects of Blood pH, pCO2, and Temperature

• Decreased blood pH, increased pCO2, and increased temperature lead to a right-shifted HbO2 dissociation curve.
  • Decreased blood pH = blood is more acidic (increased blood H+ ion concentration).
  • Blood CO2 and blood H+ ion concentration are proportional to each other (evidenced in the carbonic acid buffering equation).
  • H+ ions, CO2, and heat are all metabolic byproducts.
  • Binding of H+ to Hb slightly alters Hb structure, which drives off O2.
  • Result: O2 and Hb bind less tightly.

Arterial Blood Gas Terminology

• Hypoxemia: low PaO2.
• Hypocapnia: low PaCO2.
• Hypercapnia: high PaCO2.
• Acidemia: pH < 7.35.
• Alkalemia: pH > 7.45.

Signs and Symptoms Associated with Hypoxemia

• Shortness of breath and rapid breathing
• Coughing
• Wheezing
• Rapid heart rate
• Headache
• Confusion
• Restlessness
• Anxiety
• Changes in the color of the skin
• Sweating