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Respiratory System

• Major functions of respiratory system: supply body with O2 for cellular respiration and dispose of CO2, a waste product of cellular respiration • Respiratory and circulatory system are closely coupled • Also functions in olfaction and speech

Respiratory System

Respiration involves four processes 1. Pulmonary ventilation (breathing): movement of air into Respiratory and out of lungs system 2. External respiration: exchange of O2 and CO2 between lungs and blood

3. Transport of O2 and CO2 in blood 4. Internal respiration: exchange of Circulatory system O2 and CO2 between systemic blood vessels and tissues

The Major Respiratory Organs

Conducting Zone Respiratory Zone

Nasal cavity Oral cavity Nostril Pharynx Larynx

Trachea Left main Carina of (primary) trachea bronchus

Right main Left lung (primary) bronchus Diaphragm Right lung

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Anatomical Relationships Of Organs In The Thoracic Cavity

Intercostal muscle Rib Parietal pleura Lung Pleural cavity Visceral pleura Trachea Thymus Apex of lung Left Right superior lobe superior lobe Horizontal fissure Oblique fissure Right middle lobe Left inferior Oblique fissure lobe Right inferior lobe Heart (in mediastinum) Diaphragm Base of lung Cardiac notch Anterior view. The lungs flank mediastinal structures laterally.

Hilum of the Lung Apex of lung

Pulmonary artery

Left Left main superior lobe bronchus Oblique fissure Pulmonary vein Left inferior lobe Cardiac impression Hilum of lung Oblique Aortic fissure impression Lobules

Photograph of medial view of the left lung.

Anatomical relationships of organs in the thoracic cavity

Esophagus Posterior Vertebra (in mediastinum) Root of lung at hilum Right lung • Left main bronchus • Left pulmonary artery Parietal pleura • Left pulmonary vein Visceral pleura Left lung Pleural cavity Thoracic wall Pulmonary trunk Pericardial membranes Heart (in mediastinum) Anterior mediastinum Sternum Anterior Transverse section through the thorax, viewed from above. Lungs, pleural membranes, and major organs in the mediastinum are shown.

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Nasal Cavity Passageway: • Moistens and warms entering air

Posterior Sphenoidal Cribriform • Filters and cleans nasal sinus plate of • Resonating chamber for speech aperture ethmoid bone • Location of olfactory receptors Conchae: • Increase Frontal sinus surface area Nasal cavity of mucosa • Nasal conchae (superior, middle • Increase air and inferior) turbulence • Nasal meatuses (superior, middle, and inferior)

• Nasal vestibule

• Nostril

Uvula Soft Tongue Hard • Vibrissae palate palate • Mucus membranes • Pseudostratified ciliated epithelium • Goblet cells • Cilia – directed toward pharynx • Seromucous glands: lysozyme • Defensins act at microbe membranes

Pharynx, Larynx, and Upper Trachea

Air or Posterior nasal Air and food aperture Nasopharynx passageway • Pharyngeal tonsil • Opening of pharyngotympanic ‘Eustachian’ tube tube

Unencapsulated Oropharynx Hard palate • Palatine tonsil Soft palate lymphoid nodules • Isthmus of the fauces Tongue Lingual tonsil Epiglottis (elastic Laryngopharynx Hyoid bone Larynx cartilage) protects • Epiglottis airway (glottis) • Vestibular fold • Thyroid cartilage from food/drink Esophagus • Vocal fold • Cricoid cartilage during swallowing Trachea Thyroid gland

(b) Structures of the pharynx and larynx

The Larynx

Epiglottis

Body of hyoid bone Thyrohyoid membrane Thyroid cartilage Laryngeal prominence (Adam’s apple) Cricothyroid ligament Cricoid cartilage

• Location of vocal folds (known as the true vocal cords) Tracheal cartilages • Airway – in and out – return to pseudostratified ciliated Anterior view epithelium

• Voice production

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Movements of the vocal folds.

Epiglottis Vestibular fold (false vocal cord) Vocal fold (true vocal cord) Glottis Inner lining of trachea Cuneiform cartilage Corniculate cartilage

Vocal folds in closed position; Vocal folds in open position; closed glottis open glottis

https://youtu.be/9Tlpkdq8a8c

Tissue Composition Of The Tracheal Wall

Posterior Mucosa – pseudostratified ciliated epithelium

Esophagus Submucosa - glandular Trachealis Lumen of Seromucous gland trachea in submucosa Hyaline cartilage

Adventitia Anterior • ‘Windpipe’ • Supported by C – shaped rings of hyaline cartilage – prevents closing even when thoracic pressure changes and food in esophagus pushes • Carina

Goblet cell Mucosa • Pseudostratified ciliated columnar epithelium • Lamina propria (connective tissue) Submucosa Seromucous gland in submucosa Hyaline cartilage

Tissue composition of the tracheal wall Photomicrograph of the tracheal wall (320 )

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Conducting Zone Passages

Trachea

Superior lobe of left lung Left main (primary) At level of bronchus T7 Superior lobe of right lung Lobar (secondary) bronchus

Segmental Middle lobe (tertiary) of right lung bronchus

Inferior lobe Inferior lobe of right lung of left lung • Three lobes on right; two lobes on left • Segments • Lobules • C-rings replaced by hyaline plates • Elastic tissue present - stroma • Pseudostratified ciliated eventually replaced by simple columnar then cuboidal • Smooth muscle in walls increases

Respiratory Zone Structures

Alveoli Alveolar duct

Respiratory Alveolar duct bronchioles Terminal Alveolar bronchiole sac

• Terminal bronchioles <0.5 mm in diameter • No cartilage involvement • Smooth muscle dominates • Epithelium now non-ciliated cuboidal in the smallest tubes • Mucus production limited then ends

Respiratory Zone Structures

Respiratory bronchiole

Alveolar Alveolar duct pores

Alveoli

Alveolar sac

Alveolar surface area = 90 m2 or 969 ft2 in healthy lungs of adult male Floor space of a small apartment

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Alveoli And The Respiratory Membrane

Terminal bronchiole Respiratory bronchiole

Smooth muscle

Elastic fibers

Alveolus

Capillaries

Respiratory membrane is combination of alveolar squamous cells, basal lamina, and capillary endothelial cells • 0.5 µm thick blood-air barrier

Alveoli And The Respiratory Membrane

Red blood cell

Nucleus of type I alveolar cell

Alveolar pores

Capillary

O2 Capillary

CO2 Macrophage Alveolus Endothelial cell nucleus Alveolus

Alveolar epithelium Respiratory Fused basement membranes membrane of alveolar epithelium and capillary endothelium Capillary endothelium Alveoli (gas-filled Red blood cell Type II alveolar cell Type I air spaces) in capillary (secretes surfactant) alveolar cell

Detailed anatomy of the respiratory membrane • Type I alveolar cells = simple squamous supported by thin basement membrane, dominate • Type II alveolar cells = scattered surfactant-producing cuboidal cells, produce antimicrobials also. Surfactant decreases cohesiveness (surface tension) of water on surface, reducing tendency to collapse • Alveolar pores share air between adjacent alveoli • Alveolar macrophages move along surface eventually being swept out

Pulmonary Ventilation • Boyle’s law: relationship between pressure and volume of a gas • Gases always fill the container they are in • If amount of gas is the same and container size is reduced, pressure will increase • So pressure (P) varies inversely with volume (V) • Mathematically:

• P1V1 = P2V2

When atmospheric pressure and intrapulmonary pressure are the same, no air moves • muscles acting on the lungs change the intrapulmonary pressure

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Atmospheric pressure (Patm) 0 mm Hg (760 mm Hg at sea level) Parietal pleura Thoracic Visceral pleura wall Pleural cavity containing pleural fluid

Transpulmonary pressure 4 mm Hg (the difference between 0 mm Hg and 4 mm Hg) Must be maintained or lung collapses

 4

0 Intrapleural

pressure (Pip) 4 mm Hg (756 mm Hg) Lung Strong adhesive forces Diaphragm Intrapulmonary between visceral and pressure (P ) pul parietal pleurae keeps Pip 0 mm Hg negative (760 mm Hg)

Changes in anterior-posterior and Changes in lateral dimensions Sequence of events superior-inferior dimensions (superior view) • Normal inspirational muscle 1 Inspiratory muscles contract (diaphragm descends; rib cage contractions lead to 500 ml change in rises). volume Ribs are elevated and • Diaphragm is dominant inspirational 2 Thoracic cavity volume sternum flares increases. as external muscle intercostals contract.

3 Lungs are stretched; intrapulmonary volume increases. External intercostals

Inspiration contract. 4 Intrapulmonary pressure drops (to1 mm Hg).

5 Air (gases) flows into lungs Diaphragm moves down its pressure gradient until inferiorly during intrapulmonary pressure is 0 contraction. Forced inspirations recruit the scalenes, (equal to atmospheric pressure). sternocleidomastoids, pectoralis minors, and erector spinae 1 Inspiratory muscles relax (diaphragm rises; rib cage descends due to recoil of costal cartilages). Ribs and sternum are 2 Thoracic cavity volume depressed as decreases. external intercostals relax. 3 Elastic lungs recoil passively; intrapulmonary External volume decreases. intercostals Expiration relax.

4 Intrapulmonary pressure rises (to 1 mm Hg).

Diaphragm 5 Air (gases) flows out of lungs moves down its pressure gradient superiorly until intrapulmonary pressure is 0. as it relaxes. Normal expiration is passive

Gas Exchange: Basic Properties of Gases • Dalton’s law of partial pressures • Total pressure exerted by mixture of gases is equal to sum of pressures exerted by each gas • Partial pressure • Pressure exerted by each gas in mixture • Directly proportional to its percentage in mixture

Example: atmospheric pressure = 760 mmHg; O2 = 20.95% of atmospheric air at sea level

760 mmHg x 20.95% O2 = 159.2 mmHg O2, the partial pressure of oxygen in air • Henry’s law • For gas mixtures in contact with liquids: • Each gas will dissolve in the liquid in proportion to its partial pressure • At equilibrium, partial pressures in the two phases will be equal • Amount of each gas that will dissolve depends on:

• Solubility: CO2 is 20 more soluble in water than O2, and little N2 will dissolve • Temperature: as temperature of liquid rises, solubility decreases

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Inspired air: Alveoli of lungs:

PO2 160 mm Hg PO2 104 mm Hg PCO2 0.3 mm Hg PCO2 40 mm Hg

CO O 2 2 O CO Partial Pressure O2 CO2 2 2 External Gradients respiration

Pulmonary Alveoli Pulmonary Promoting Gas arteries veins (P O2 Movements In 100 mm Hg) Blood leaving Blood leaving tissues and lungs and The Body entering lungs: entering tissue PO2 40 mm Hg capillaries: P 100 mm Hg PCO2 45 mm Hg O2 PCO2 40 mm Hg

Heart O2 CO2 O2 CO2

Systemic Systemic veins arteries

Internal respiration CO2 O2

Tissues:

PO2 less than 40 mm Hg O CO 2 2 PCO2 greater than 45 mm Hg

Oxygen Transport

• Association of oxygen and hemoglobin • Each Hb molecule is composed of four polypeptide chains, each with a iron-containing heme group • So each Hb can transport four oxygen molecules

• Oxyhemoglobin (HbO2): hemoglobin-O2 combination • Reduced hemoglobin (deoxyhemoglobin) (HHb): hemoglobin that has released O2

The oxygen-hemoglobin dissociation curve will help you understand how the properties of hemoglobin (Hb) affect oxygen binding in the lungs and oxygen release in the tissues.

In the lungs, where PO2 is high (100 mm Hg), Hb is almost This axis tells you how much fully saturated (98%) with O2.

O2 is bound to Hb. At 100%, each Hb molecule has 4 bound oxygen molecules. Hemoglobin

100

Oxygen

If more O2 is present, 80 more O2 is bound. However, because of Hb’s properties (O2 60 binding strength changes with saturation), this is an S-shaped curve.

40

saturationhemoglobinof 2

20 Percent O Percent

0 0 20 40 60 80 100

PO2 (mm Hg)

This axis tells you the relative amount (partial pressure) of O2 dissolved in the fluid In the tissues of other organs, surrounding the Hb. where PO2 is low (40 mm Hg), Hb is less saturated (75%) with O2.

This is a standard curve under ideal conditions. In the body, temperature, RBC

waste products, [CO2], and blood pH all affect the ability of hemoglobin to hold oxygen, aka hemoglobin affinity for oxygen

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Oxygen Transport

Influence of other factors on hemoglobin saturation • 2,3-bisphosphoglycerate (BPG) is produced by RBCs during glycolysis • BPG levels rise when oxygen levels are low

• Increasing BPG binding to Hb: release more O2 • As tissues metabolize glucose, they use O2, causing: • Increases in P and H+ in capillary blood CO2 • Declining blood pH (acidosis) and increasing Pco2 cause Hb-O2 bond to weaken • Referred to as Bohr effect

• O2 unloading occurs where needed most • Heat production in active tissue directly and indirectly decreases Hb affinity for O2

• Allows increased O2 unloading to active tissues

Changing Delivery of Oxygen by Hemoglobin • At rest, hemoglobin carries more oxygen than it actually delivers to tissues • Only 23% of what is carried is delivered

• Tissue Po2 determines % liberated • Hemoglobin saturation (all hemes carrying oxygen) changes with changing conditions • temperature and pH-related conformational shift in hemoglobin, ↑BPG reduces its capacity to carry

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100 10°C 20°C 80 38°C 43°C

60

40 Normal body

saturation of saturation hemoglobin temperature 2 20

0 Percent O Percent 20 40 60 80 100

PO2 (mm Hg)

Decreased carbon dioxide  (PCO 20 mm Hg) or H (pH 7.6) 100 2

80

Normal arterial carbon dioxide 60 (PCO2 40 mm Hg) or H (pH 7.4) 40

saturation saturation of hemoglobin Increased carbon dioxide 2

(PCO2 80 mm Hg) or H (pH 7.2)

20 Percent Percent O 0 20 40 60 80 100

PO2 (mm Hg)

Carbon Dioxide Transport

• Occurs primarily in RBCs, where enzyme carbonic anhydrase reversibly and rapidly catalyzes this reaction – • In systemic capillaries, after HCO3 is created, it quickly diffuses from RBCs into plasma – – • Outrush of HCO3 from RBCs is balanced as Cl moves into RBCs from plasma • Referred to as chloride shift

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Carbon Dioxide Transport

Encouraging CO2 exchange at tissues and at lungs

• Haldane effect - amount of CO2 transported is affected by P O2 • The lower the P and Hb O saturation, the more CO Hb O2 2 2 can carry • Unsaturated Hb buffers H+ and forms carbaminohemoglobin more easily

• Bohr effect - at tissues, as more CO2 enters blood, more oxygen dissociates from hemoglobin

• As HbO2 releases O2, it more readily forms carbaminohemoglobin

Transport and Exchange of CO2 and O2 at Tissues

Tissue cell Interstitial fluid

CO2 CO2 (dissolved in plasma 7-10%) Binds to Slow plasma   CO2 CO2  H2O H2CO3 HCO3  H proteins CO  2 HCO3 As bicarbonate ion 70% Chloride Cl shift Fast (in) via   Cl CO2 CO2  H2O H2CO3 HCO3  H transport Carbonic protein

CO2 anhydrase HHb

CO2 (about 20%) CO2  Hb HbCO2 (Carbamino- hemoglobin) deoxyhemoglobin

Red blood cell HbO2 O2  Hb oxyhemoglobin CO2 O2

O2 O2 (dissolved in plasma) Blood plasma

Oxygen release and carbon dioxide pickup at the tissues Partially saturated, fully saturated Hb Affinity for O2 varies with the extent of oxygen saturation Rate of Hb binding/releasing oxygen dependent on PO2, temperature, blood pH, PCO2, and BPG (2,3 bisphosphoglycerate)

Transport and exchange of CO2 and O2 at lungs Alveolus Fused basement membranes

CO2 CO2 (dissolved in plasma)

Slow   CO2 CO2  H2O H2CO3 HCO3  H

 HCO3  Chloride Cl shift (out) via Fast   transport CO2 CO2  H2O H2CO3 HCO3  H Carbonic protein anhydrase Cl

CO2 CO2  Hb HbCO2 (Carbamino- hemoglobin) Red blood cell  O2  HHb HbO2  H

O2

O2 O2 (dissolved in plasma) Blood plasma

Oxygen pickup and carbon dioxide release in the lungs

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Respiratory centers in the brain stem Pons Medulla Pontine respiratory centers interact with the medullary respiratory centers to smooth the respiratory pattern.

Ventral respiratory group (VRG) contains rhythm generators whose output drives respiration.

Pons Medulla

Dorsal respiratory group (DRG) integrates peripheral sensory input and modifies the rhythms generated by the VRG.

Phrenic nerve (from C3, C4, C5) innervates the diaphragm.

Intercostal nerves Diaphragm

External intercostal muscles

Arterial PCO2

PCO2 decreases pH in brain extracellular fluid (ECF) Changes in PCO Central chemoreceptors Peripheral chemoreceptors 2 in brain stem respond to in carotid and aortic bodies H in brain ECF (mediate (mediate 30% of the CO regulate 2 response) 70% of the CO2 response) ventilation Afferent impulses by a Medullary respiratory centers negative Efferent impulses feedback Respiratory muscle mechanism

Ventilation (more CO2 exhaled)

Initial stimulus

Physiological response Arterial PCO2 and pH return to normal Result

Higher brain centers (cerebral cortex—voluntary control over breathing)

Other receptors (e.g., pain)  and emotional stimuli acting through the hypothalamus

 Respiratory centers (medulla and pons)

Peripheral chemoreceptors  O ,CO ,H  2 2  Stretch receptors  in lungs Central chemoreceptors   CO2,H  Irritant receptors Receptors in muscles and joints Neural and chemical influences on brain stem respiratory centers

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Responding to Changing Conditions

• What causes change? • Responses: • Reserve capacity built in • In volume – structure of conducting passages, muscular involvement, lung involvement • Dilation • Recruitment • In blood flow – adjustment in heart rate and lung involvement

• In hemoglobin – changes in affinity for O2 • In respiratory rate – stimulation from the brain

Respiratory Volumes And Capacities

6000

5000 Inspiratory reserve volume Inspiratory 3100 ml capacity 4000 3600 ml Vital Total lung capacity capacity 4800 ml 6000 ml 3000

Tidal volume 500 ml Milliliters (ml) Milliliters 2000 Expiratory reserve volume Functional 1200 ml residual 1000 capacity Residual volume 2400 ml 1200 ml 0 Spirographic record for a male

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Respiratory Volumes And Capacities

Adult male Adult female Measurement average value average value Description

Tidal volume (TV) 500 ml 500 ml Amount of air inhaled or exhaled with each breath under resting conditions Inspiratory reserve Amount of air that can be forcefully inhaled after a normal tidal volume (IRV) 3100 ml 1900 ml volume inspiration Respiratory volumes Expiratory reserve Amount of air that can be forcefully exhaled after a normal tidal 1200 ml 700 ml volume (ERV) volume expiration

Residual volume (RV) 1200 ml 1100 ml Amount of air remaining in the lungs after a forced expiration

Maximum amount of air contained in lungs after a maximum Total lung capacity (TLC) 6000 ml 4200 ml inspiratory effort: TLC = TV  IRV  ERV  RV Maximum amount of air that can be expired after a maximum 4800 ml 3100 ml Vital capacity (VC) inspiratory effort: VC = TV  IRV  ERV Respiratory capacities Maximum amount of air that can be inspired after a normal tidal Inspiratory capacity (IC) 3600 ml 2400 ml volume expiration: IC = TV  IRV Functional residual Volume of air remaining in the lungs after a normal tidal volume 2400 ml 1800 ml capacity (FRC) expiration: FRC = ERV  RV

Summary of respiratory volumes and capacities for males and females

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