The Respiratory System

Respiratory System

Functions of the Respiratory System

• Supply O_2 to cells.

• Eliminate CO_2.

• Produce sounds for vocalization.

• Trap and dissolve small clots.

• Produce histamine, angiotensin I.

• Remove neurotransmitters (catecholamines).

Basic Processes

• Ventilation: Movement of air into (inspiration) and out of (expiration) the lungs.

• External Respiration: Diffusion of gases between alveolar air and pulmonary blood.

• Blood Gas Transport: Mechanisms to transport O2 and CO2 through the bloodstream.

• Internal Respiration: Diffusion of gases between tissue capillaries and interstitial fluid.

Basic Organization

• Organs of the Respiratory Tract:

  • Nose

  • Pharynx

  • Larynx

  • Trachea

  • Bronchial tree (bronchi, bronchioles, terminal bronchioles, respiratory bronchioles)

  • Lungs (containing alveoli)

• Functional Divisions:

  • Conducting Passages: Carry air into and out of the body but are not involved in gas exchange.

    • Include: nose, pharynx, trachea, larynx, bronchi, bronchioles, and terminal bronchioles.

  • Respiratory Passages: Used for gas exchange with the blood.

    • Include: respiratory bronchioles, alveoli, and alveolar ducts.

Trachea

• Location:

  • Extends from the inferior larynx (C6) to the carina (sternal angle T4-T5 in adults).

  • Lower portion is in the mediastinum.

  • Lies in the midline of the thorax, anterior to the esophagus.

• Functions:

  • Forms a patent airway.

  • Ciliated epithelium filters inspired air.

  • Carina has sensory receptors that initiate cough reflexes.

Bronchial Tree

• General Trends: As the bronchial tree branches into smaller tubes:

  1. Cartilage diminishes and is replaced with smooth muscle

     • Bronchial walls have cartilage plates to keep them open.

     • Bronchioles have smooth muscle in their walls and no cartilage.

     • Elastic fibers are present in all tube walls.

  2. Epithelium becomes flatter

     • Larger bronchi have pseudostratified ciliated columnar epithelium.

     • Terminal bronchioles have cuboidal epithelium.

     • Alveoli have simple squamous epithelium.

  3. Other

     • Mucus and cilia remove debris in bronchi; macrophages remove debris in smaller tubes.

• Structures of the Bronchial Tree

  • Primary Bronchi:

    • Made of cartilage with some smooth muscle. Lined with pseudostratified ciliated epithelium.

    • Right and left primary bronchi form when the trachea divides at the sternal angle.

    • Right primary bronchus is shorter, wider, and more vertical than the left. Contains numerous goblet cells.

    • One primary bronchus per lung.

  • Secondary (Lobar) Bronchi:

    • Made of cartilage with greater amounts of smooth muscle. Lined with pseudostratified epithelium, but the epithelium is shorter.

    • Three lobar bronchi supply the three lobes of the right lung, and two lobar bronchi supply the lobes of the left lung.

  • Tertiary (Segmental) Bronchi:

    • Made of cartilage that forms irregular rings, with more smooth muscle. Pseudostratified epithelium is present, but the cells are very short.

    • Each tertiary bronchus supplies a division of a lobe called a bronchopulmonary segment.

  • Bronchioles:

    • Contain little or no cartilage and are made primarily of smooth muscle (diameter less than 1 mm). Lined with cuboidal epithelium with a few ciliated cells and a few mucus-secreting cells.

    • Small branches of tertiary bronchi.

  • Terminal Bronchioles:

    • Lack cartilage completely and walls are made entirely of smooth muscle. Lined with cuboidal epithelium.

    • Diameter is less than 0.5 mm. Terminal bronchioles lead to alveolar ducts which invade alveolar sacs.

  • Alveoli:

    • Walls are primarily made of simple squamous epithelium (Type I cells).

    • Cuboidal cells (Type II cells) secrete surfactant.

    • Macrophages (dust cells) are present.

    • Clusters of alveoli are called alveolar sacs. Adjacent alveoli are connected by alveolar pores.

Lungs

• Basic Anatomy

  • Right Lung: Upper lobe, middle lobe, lower lobe separated by horizontal and oblique fissures.

  • Left Lung: Upper lobe, lower lobe separated by the oblique fissure.

  • Apex: Conical, superior tip of each lung.

  • Base: Concave, inferior surface of each lung; rests on the diaphragm.

  • Hilus: Indentation on the mediastinal surface that receives blood vessels and bronchi.

  • Mediastinal Surface: Borders the mediastinum.

  • Costal Surface: Posterior, lateral, and anterior surfaces in contact with the ribs.

  • Diaphragmatic Surface: Inferior surface in contact with the diaphragm.

• Lung Tissue:

  • Elastic connective tissue in which the bronchial tree and alveoli are embedded.

• Nerve Supply to the Lungs:

  • Sympathetic Nervous System (SNS): Dilates bronchioles and inhibits mucus secretion.

  • Parasympathetic Nervous System (PNS): Constricts bronchioles and stimulates mucus secretion.

• Circulation to the Lungs:

  • Pulmonary Circulation enables blood oxygenation.

    • Right ventricle → pulmonary arteries → pulmonary capillaries → pulmonary veins → left atrium.

  • Bronchial Pathway enables lungs to be nourished.

    • Aorta → bronchial arteries → bronchial capillaries → bronchial veins → superior vena cava → right atrium.

Pleura

• Pleura: Serous membranes that surround each lung.

  • Visceral Pleura: Adheres to the surface of the lung.

  • Parietal Pleura: Lines the thoracic cavity and the thoracic surface of the diaphragm.

  • Pleural Cavity: Contains a small amount of pleural fluid.

• Functions of the Pleurae/Pleural Fluid:

  • Maintaining the boundaries of the pleural cavity.

  • Reduce friction and facilitate lung movement.

  • Create surface tension which draws the surface of the lungs to the thoracic wall.

Respiratory Membrane

• O2 and CO2 cross the respiratory membrane during external respiration.

• Structure:

  • Alveolar endothelium (simple squamous alveolar epithelium).

  • Basal lamina.

  • Capillary endothelium (simple squamous capillary endothelium).

  • Type I and Type II alveolar cells.

• Factors Governing Diffusion Rate:

  • Rate of diffusion depends on:

    • Solubility of the gas in plasma.

    • Characteristics of the respiratory membrane.

    • According to the equation: Diffusion Rate ∝ (Surface Area x Pressure Difference) / Thickness

  • If membrane thickens, the rate of diffusion decreases (e.g., pneumonia).

  • If surface area decreases, the rate of diffusion decreases (e.g., emphysema).

Ventilation

• Air moves from regions of high pressure to low pressure.

• Ventilation is a mechanical process dependent on volume changes in the thoracic cavity.

• If thoracic volume changes, thoracic pressure changes.

• If thoracic volume increases, gas pressure in the thorax decreases.

• If thoracic volume decreases, pressure increases.

• All atmospheric pressures refer to pressures at the nose.

• Ventilation (breathing) consists of:

  1. Inspiration (inhalation): Air moves from the atmosphere into the alveoli.

  2. Expiration (exhalation): Air moves from the alveoli into the atmosphere.

• Air Movement Between the Atmosphere and Terminal Bronchioles:

  1. Air moves from areas of high pressure to areas of low pressure.

  2. Air encounters resistance as it flows.

  • Air Flow = (Pressure 1 - Pressure 2) / Resistance, where Pressure 1 is atmospheric pressure and Pressure 2 is alveolar pressure.

  • Inhalation: Atmospheric pressure > Alveolar pressure (760 mmHg - 759 mmHg = a positive pressure, therefore air enters).

  • Exhalation: Atmospheric pressure < Alveolar pressure (760 mmHg - 761 mmHg = a negative pressure, therefore air moves out).

• Air movement between terminal bronchi and alveoli: Powered by diffusion.

Pressures Involved in Ventilation

• Intra-alveolar pressure (intrapulmonary pressure): Pressure within the alveoli of the lungs; fluctuates between 759 and 761 mmHg.

• Intrapleural pressure: Pressure within the pleural cavity; always less than the pressure in the lungs by about 4 mmHg.

• Atmospheric pressure: Pressure exerted by gases in the atmosphere; at sea level, averages 760 mmHg.

• Intrapulmonary pressure falls below atmospheric pressure during inhalation and rises above atmospheric pressure during exhalation.

  • During Inspiration: Atmospheric pressure = 760 mmHg, Intra-alveolar pressure = 759 mmHg.

  • During Expiration: Atmospheric pressure = 760 mmHg, Intra-alveolar pressure = 761 mmHg.

• Boyle's Law: Gas pressure is inversely related to the space (volume) that it occupies

• Expansion of alveoli causes decreased alveolar gas pressure and promotes inspiration; Compression of alveoli causes increased alveolar gas pressure and promotes expiration.

• Factors That Promote Expansion:

  1. Pleural fluid surface tension

  2. Negative intrapleural pressure

  3. Structural elements of the lungs (alveolar septal walls)

• Factors That Promote Compression:

  1. Alveolar fluid surface tension

  2. Elastic recoil of the lungs

• Compliance: Ability of the lungs to expand, important for inspiration (high compliance = easy expansion).

• Elasticity: Ability of the lungs to recoil, important for expiration.

• Forced expiration can be accomplished by actively recruiting additional muscles (abdominal muscles: external oblique, internal oblique, transverse abdominus; thoracic muscles: internal intercostals, latissimus dorsi, quadratus lumborum).

Air Flow Resistance

• The pressure gradient between the alveoli and the atmosphere is the force that drives lung ventilation.

• Driving force is opposed by resistance, the greatest resistance is encountered in medium sized bronchioles.

• Resistance = \frac{length \, of \, tube \, X \, viscosity}{radius^4}

• Air Flow = (Pressure 1 - Pressure 2) / Resistance

• Factors Increasing Resistance:

  • Bronchoconstriction (PNS, acetylcholine, histamine).

  • Solid obstructing tumors.

  • Mucus accumulation.

  • Inflammation.

• Factors Decreasing Resistance:

  • Bronchodilation (SNS, epinephrine, increased pO2, decreased pCO2).

External/Internal Respiration

• Dalton's Law of Partial Pressures: The total pressure exerted by a mixture of gases is the sum of the pressures exerted individually by each of the gases in the mixture.

  • The individual pressure of a single gas in a mixture is called partial pressure (p).

  • 760 mmHg = pN2 + pO2 + pCO2 + other gases…..

• pO_2 = 20.9\% \, X \, 760 \, mmHg = 0.209 \, X \, 760 \, mmHg = 159 \, mmHg

• pCO_2 = 0.04\% \, X \, 760 \, mmHg = .0004 \, X \, 760 \, mmHg = 0.3 \, mmHg

• Henry's Law: When a mixture of gas comes into contact with a liquid, a gas will dissolve into the liquid in proportion to its partial pressure.

• Gases diffuse into and out of liquids from high to low partial pressure.

• Other factors affecting gas movement:

  • Properties of the diffusion barrier (as thickness increases, rate of transfer decreases).

  • Gas solubility (as solubility increases, rate of transfer increases).

  • Temperature of the liquid (as temperature of the liquid increases, gas solubility decreases).

• External Respiration: The diffusion of gases between the alveolar air and the blood in the pulmonary capillaries across the respiratory membrane. O2 diffuses into the blood and CO2 diffuses out of the blood.

• Internal Respiration: The diffusion of gases between the blood of tissue capillaries and interstitial fluid. CO2 diffuses into the blood and O2 diffuses out of the blood.

• Arterial Blood: pO2 = 100 mmHg, pCO2 = 40 mmHg.

• Venous Blood: pO2 = 40 mmHg, pCO2 = 45 mmHg.

Partial Pressures

• Alveoli: pO2 = 104 mmHg, pCO2 = 40 mmHg

• Arterial blood entering tissue: pO2 = 104 mmHg, pCO2 = 40 mmHg

• Tissue interstitial fluid: pO2 < 40mmHg, pCO2 = 45 mmHg

• Venous blood leaving tissue: pO2 = 40mmHg, pCO2 = 45 mmHg

• Venous blood entering alveolar capillaries: pO2 = 40mmHg, pCO2 = 45 mmHg

• Arterial blood leaving alveolar capillaries: pO2 = 104mmHg, pCO2 = 40mmHg

• Ventilation-Perfusion Coupling:

  • When alveolar pO2 is low, local arterioles constrict.

  • When alveolar pO2 is high, local arterioles dilate.

  • When alveolar pCO2 is low, bronchioles constrict.

  • When alveolar pCO2 is high, bronchioles dilate.

Blood Gas Transport: O2

• Oxygen transport:

  • 1.5% is dissolved in the plasma; this is the O_2 that exerts partial pressure.

  • 98.5% is carried by hemoglobin in RBC’s: Hb + 4O2 \rightleftharpoons Hb(O2)_4 (reduced hemoglobin <-> oxyhemoglobin).

  • Most important factor in determining how much O_2 combines with Hb is pO2.

• Oxyhemoglobin Dissociation Curve describes the relationship between partial pressure and the % of O_2 binding sites on Hb that are full.

• % saturation (% HbO2) in arterial blood, at pO2 = 104 mmHg

• % saturation (% HbO2) in venous blood, at pO2 = 40mmhg

• Under normal circumstances, tissue only receive 25% of the O2 delivered to them by HbO2

• At pO2 = 60mm Hg Hb is 90% saturated, additional in pO2 has little effect

• At pO2 less than 40mm Hg the affinity of O_2 for Hb is low.

• The extent to which hemoglobin binds to oxygen depends on several factors, including pO2, pCO2, temperature and blood BPG levels.

• The oxygen-hemoglobin dissociation curve demonstrates the effect of pO2 and the principle of cooperative binding

• Factors that Favor a “Right Shift” (Reduce HbO2 Affinity):

  • Increased temperature

  • Elevated pCO2

  • Reduced pH

  • Elevated 2,3 bisphosphoglycerate

• Factors that Favor a “Left Shift” (Increase HbO2 Affinity):

  • Decreased temperature

  • Reduced pCO2

  • Elevated pH

  • Reduced 2,3 bisphosphoglycerate

• Bohr Effect: The effect of pH on hemoglobin/O2 affinity; low pH weakens the hemoglobin-O2 bond.

• When tissues are active:

  • Increased CO2 is released

  • This increases H+ concentration (lowers pH)

  • At higher p CO2 and lower pH, O2 has a lower affinity for Hb

  • Therefore more O2 is released

• Globin binds to NO and protects it from being destroyed by heme.

• when HBO2 circulates to tissues, it releases both O2 and NO.

• NO induces vasodilation and increases blood flow.

Carbon Dioxide Transport

• Carbon dioxide is carried in three ways:

  • 7-10% of the CO2 is dissolved in the plasma; this is the pCO2 that exerts partial pressure.

  • 20-30% of the CO2 diffuses into red blood cells and attaches to hemoglobin (not to heme, the globin portion): Hb + CO2 \rightleftharpoons HbCO2 (hemoglobin <-> carbaminoglobin).

  • 60-70% of the CO2 diffuses into the red blood cell and is converted to HCO3^- (bicarbonate) which is then carried in the plasma. CO2 + H2O \rightleftharpoons H^+ + HCO3^-

• Haldane Effect: Reduced Hb has a greater capacity to bind CO_2 than HbO2 does.

Neural Control of Ventilation

• Two clusters of neurons involved in the regulation of ventilation rate:

  • Ventral Respiratory Group (VRG):

    • Location: ventral medulla; extends from the pons to the spinal cord

    • Function: sets the basic ventilation rate, contains inspiratory neurons and expiratory neurons

  • Dorsal Respiratory Group (DRG):

    • Location: dorsal medulla, near the root of cranial nerve IX

    • Function: integrate impulses from peripheral stretch receptors and chemoreceptors and relays them to the ventral respiratory group

• Ventral Respiratory Group :

  • Inspiratory Neurons Fire Impulses are carried to the diaphragm by the phrenic nerve and the external intercostal muscles by the intercostal nervesThe thorax enlarges and inspiration occurs Inspiration lasts for 2 seconds

  • Expiratory Neurons Fire Inhibitory impulses are delivered to the inspiratory neurons; the diaphragm and the external intercostals relax The thorax compress and exhalation occurs Expiration lasts for 3 seconds

• Pontine Respiratory Center: Modifies the basic rhythm in concert with vocalization, sleep, exercise and other activities.

• Apneustic Center: Assists in the transition between inspiration and expiration.

• Inflation Reflex (Hering Breuer Reflex): Lung inflation activates stretch receptors in the visceral pleura and in the conducting portions of the bronchial tree vagal afferents inhibit VRG neurons phrenic nerve is inhibited, inspiration stops

• The most important regulator of ventilation is arterial pCO2 concentrations.

• Peripheral chemoreceptors is 40 mmHg

• Central Chemoreceptors :

  • CO2 diffuses into the CSF and reacts with H2O to form H2CO3

  • the H+ that is generated activates central chemoreceptors

  • decreased CSF pH leads to hyperventilation

  • increased CSF pH leads to hypoventilation

• Normal arterial pO2 is 100 mmHg . if pO2 falls below 60 mmHg, hyperventilation occurs ventilation rate is less sensitive to pO2 than pCO2

• Arterial pH decreases in arterial pH lead to hyperventilation and increases in arterial pH lead to hypoventilation, even if the pO2 and pCO2 are normal

Terms used for ventilation

• eupnea: normal quiet breathing

• apnea cessation of breathing

• hyperpnea deep, vigorous breathing

• dyspnea difficult, labored breathing

• tachypnea rapid breathing

Disorders Associated With Respiration

• Emphysema:. Cause(s): decreased  antitrypsin activity increased elastase activity compounded by smoking, pollution, aging and COPD, Characteristics: permanent enlargement of respiratory bronchioles, alveolar ducts and alveoli destruction of alveolar walls loss of elasticity Leads to dyspnea, enlarged (barrel) chest, low diffusing capacity

• Asthma Cause(s): Intrinsic Asthma: caused by Type I hypersensitivity Extrinsic Asthma nonimmune; caused by infection, stress, inhaled irritants, drug ingestion or exercise, Characteristics: chronic airway inflammation and hyperresponsive tracheobronchial tree, leads to dyspnea, coughing wheezing and copious mucus secretion

• Tuberculosis Cause: Infection with Mycobacterium tuberculosis Characteristics: reactivation or reinfection produces respiratory symptoms: chest pain, bloody sputum, granulomas and lung cavitation can spread to other organs such as the skeleton, digestive viscera, adrenal glands, genitourinary tract and the heart

• Bronchogenic Carcinoma :Cause: genetic causes; smoking, air pollution, radiation exposure, industrial chemicals, Characteristics: cough, weight loss, chest pain and dyspnea; increased sputum production; tumor obstruction of airways; frequent metastasis

• Cystic Fibrosis Cause: defective gene encoding Cl- transporter in respiratory epithelial cells Characteristics: mucus accumulation leads to chronic cough, persistent lung infections, obstructive pulmonary disease digestive tract and reproductive tract also involved; malabsorption of nutrients, fat soluble vitamin deficiencies