Upper Respiratory System

�The Respiratory System

• Cells continually use O₂ & release CO₂
• Respiratory system designed for gas exchange
• Cardiovascular system transports gases in blood
• Failure of either system leads to rapid cell death from O₂ starvation

C₆H₁₂O₆ + 6O₂ 🡪 6CO₂ + 6H₂O

CO₂ + H₂O 🡨🡪 H₂CO₃ 🡨🡪 H⁺ + HCO₃^-

Gas Exchange

Ventilation

Cardiac output

External Respiration

Internal Respiration

VO_2max is dependent on O₂ transport

(Withers & Hillman, 1988)

Functions of the Respiratory System

1. Gas Exchange
2. Communication
3. Olfaction
4. Acid-base balance
5. Blood pressure regulation
6. Platelet production
7. Blood and lymph flow
8. Blood filtration
9. Expulsion of abdominal contents

Upper Respiratory Tract

The Nose

• Functions
• warms, cleanses, humidifies inhaled air
• detects odors
• resonating chamber that amplifies the voice
• Bony and cartilaginous supports (fig. 22.2)
• superior half: nasal bones medially + maxillae laterally
• inferior half: lateral and alar cartilages
• ala nasi: flared portion shaped by dense CT, forms lateral wall of each nostril

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The Pharynx

• Muscular funnel that connects the nasal and oral cavities to the larynx
• Nasopharynx
• PSCC epi.
• Oropharynx
• Strat. squamous epi.
• Laryngopharynx
• Strat. squamous epi.

The Larynx

Lower Respiratory System

Lower Respiratory Tract

Trachea

• Rigid tube 4.5 in. long and 2.5 in. in diameter, anterior to esophagus
• Supported by 16 to 20 C-shaped cartilaginous rings
• opening in rings faces posteriorly towards esophagus
• trachealis spans opening in rings, adjusts airflow by expanding or contracting
• Larynx and trachea lined with ciliated pseudostratified epithelium which functions as mucociliary escalator

Tracheal Epithelium

Bronchial Tree

• Primary bronchi
• Supply each lung
• Secondary bronchi
• Supply lobes
• Tertiary bronchi
• Supply segments
• Bronchioles (lack cartilage)
• have layer of smooth muscle
• Terminal bronchioles
• have cilia , give off 2 or more respiratory bronchioles
• Respiratory bronchioles
• divide into 2-10 alveolar ducts
• Alveolar ducts - end in alveolar sacs
• Alveoli - bud from respiratory bronchioles, alveolar ducts and alveolar sacs

Bronchial Tree

Pleural Membranes & Pleural Cavity

• Visceral pleura covers lungs
• Parietal pleura lines ribcage & covers upper surface of diaphragm
• Pleural cavity is potential space between ribs & lungs

Right lung

Aorta

Breast

Sternum

Ribs

Vertebra

Spinal cord

Pericardial

cavity

Heart

Left lung

Visceral

pleura

Pleural cavity

Parietal

pleura

Anterior

Posterior

Pleurae and Pleural Fluid

• Visceral and parietal layers
• Pleural cavity and fluid
• Functions
• reduction of friction
• creation of pressure gradient
• lower pressure assists in inflation of lungs
• compartmentalization
• prevents spread of infection

8-3 Ventilation

Pressure and Flow

• Atmospheric pressure drives respiration
• 1 atmosphere (atm) = 760 mmHg = 101 kPa
• Intrapulmonary pressure and lung volume
• pressure is inversely proportional to volume
• for a given amount of gas, as volume ↑, pressure ↓ and as volume ↓, pressure ↑
• Pressure gradients
• difference between atmospheric and intrapulmonary pressure
• created by changes in volume of thoracic cavity

Inspiration

• Quiet Inspiration
• Diaphragm (dome shaped)
• contraction flattens diaphragm
• Scalenes
• fix first pair of ribs
• External intercostals
• elevate 2 - 12 pairs
• Forceful inspiration
• Pectoralis minor, sternocleidomastoid and erector spinae muscles
• used in deep inspiration

Expiration

• Quiet Expiration
• During quiet breathing, expiration achieved by elasticity of lungs and thoracic cage
• As volume of thoracic cavity ↓, intrapulmonary pressure ↑ and air is expelled
• After inspiration, phrenic nerves continue to stimulate diaphragm to produce a braking action to elastic recoil
• Forced Expiration
• Internal intercostal muscles
• depress the ribs
• Contract abdominal muscles
• ↑ intra-abdominal pressure forces diaphragm upward, ↑ pressure on thoracic cavity

Inspiration - Pressure Changes

• ↓ intrapleural pressure
• as volume of thoracic cavity ↑,�visceral pleura clings to parietal pleura
• ↓ intrapulmonary pressure
• lungs expand with the visceral pleura
• Transpulmonary pressure
• intrapleural minus intrapulmonary pressure (not all pressure change in the pleural cavity is transferred to the lungs)
• Inflation of lungs aided by warming of inhaled air
• A quiet breathe flows 500 ml of air through lungs

Respiratory Pressure & Lung Ventilation

Pneumothorax

• Pleural cavities are sealed cavities not open to the outside
• Presence of air in pleural cavity
• loss of negative intrapleural pressure allows lungs to recoil and collapse
• Collapse of lung (or part of lung) is called atelectasis
• Injuries to the chest wall that let air enter the intrapleural space
• causes a pneumothorax
• collapsed lung on same side as injury
• surface tension and recoil of elastic fibers causes the lung to collapse

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Resistance to Airflow

• Pulmonary compliance
• Ease with which lungs & chest wall expand depends upon elasticity of lungs & surface tension
• Some diseases reduce compliance
• tuberculosis forms scar tissue
• pulmonary edema --- fluid in lungs & reduced surfactant
• Bronchiolar diameter
• primary control over resistance to airflow
• bronchoconstriction
• triggered by airborne irritants, cold air, parasympathetic stimulation, histamine
• bronchodilation
• sympathetic nerves, epinephrine

Alveolar Surface Tension

• Thin film of water necessary for gas exchange
• creates surface tension that acts to collapse alveoli and distal bronchioles
• Pulmonary surfactant (Septal cells)
• disrupts hydrogen bonds of water, ↓ surface tension
• As passages contract during expiration, surface tension naturally ↓ and surfactant concentration ↑ preventing alveolar collapse

Surfactant assists ventialtion

• Thin film of water necessary for gas exchange
• creates surface tension that acts to collapse alveoli and distal bronchioles
• Pulmonary surfactant (Septal cells)
• disrupts hydrogen bonds of water, ↓ surface tension
• As alveoli expand, the [surfactant] decreases leading to increased surface tension
• “Brake” to alveolar expansion
• Respiratory distress syndrome of premature infants

Respiratory Measures

• Forced expiratory volume (FEV)
• % of vital capacity exhaled/ time
• healthy adult - 75 to 85% in 1 sec
• Peak flow
• maximum speed of exhalation
• Minute respiratory volume (MRV)
• TV x respiratory rate, at rest 500 x 12 = 6 L/min
• maximum: 125 to 170 L/min

Alveolar Ventilation

• Dead air
• fills conducting division of airway, cannot exchange gases
• Anatomic dead space
• conducting division of airway
• Physiologic dead space
• sum of anatomic dead space and any pathological alveolar dead space
• Alveolar ventilation rate
• air that actually ventilates alveoli X respiratory rate
• directly relevant to body’s ability to exchange gases

Measurements of Ventilation

• Spirometer
• device a subject breathes into that measures ventilation
• Respiratory volumes
• tidal volume: air inhaled or exhaled in one quiet breath
• inspiratory reserve volume: air in excess of tidal inspiration that can be inhaled with maximum effort
• expiratory reserve volume: air in excess of tidal expiration that can be exhaled with maximum effort
• residual volume: air remaining in lungs after maximum expiration, keeps alveoli inflated

Lung Volumes and Capacities

Affects on Respiratory �Volumes and Capacities

• Age: ↓ lung compliance, respiratory muscles weaken
• Exercise: maintains strength of respiratory muscles
• Body size: proportional, big body has large lungs
• Restrictive disorders: ↓ compliance and vital capacity
• Often create fibrosis (scar tissue) of lungs
• Tuberculosis
• Respiratory distress in newborns
• Obstructive disorders: interfere with airflow, expiration requires more effort or less complete
• Asthma
• COPD
• Emphysema
• Chronic bronchitis

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8-4 �Control of Ventilation

Respiratory Control Centers

• Two respiratory nuclei in medulla oblongata
• Ventral Respiratory Group (VRG)
• Inspiratory neurons
• On for 2 seconds
• More frequently they fire, more deeply you inhale
• Longer duration they fire, breath is prolonged, slow rate
• Expiratory neurons
• On for 3 seconds
• Inhibit inspiratory neurons
• Also involved in forced expiration
• Dorsal Respiratory Group (DRG)
• Modulate activity of I and E neurons in VRG

Respiratory Control Centers

• Pontine Respiratory Group (PRG)
• Receives input from higher brain centers
• Hypothalamus
• Limbic system
• Cerebral cortex
• Output to DRG and VRG
• Modifies the rhythm and patterns from DRG and VRG
• Sleep
• Exercise
• Speaking
• Modified respiratory movements

VRG and DRG

• Controls basic rhythm of respiration
• Inspiration for 2 seconds, expiration for 3
• Autorhythmic cells active for 2 seconds then inactive
• Expiratory neurons inactive during most quiet breathing only active during high ventilation rates

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Voluntary Control

• Neural pathways
• motor cortex of frontal lobe of cerebrum sends impulses down corticospinal tracts to respiratory neurons in spinal cord, bypassing brainstem
• Limitations on voluntary control
• blood CO₂ and O₂ limits cause automatic respiration

Chemical Regulation of Respiration

• Central chemoreceptors
• Found in medulla oblongata
• Respond to changes in H⁺ or P_CO2 of CSF
• Hypercapnia = Increased blood P_CO2
• Peripheral chemoreceptors
• Found in carotid & aortic bodies
• Respond to changes in H⁺ , P_O2 or P_CO2
• Nerves from carotid bodies join glossopharyngeal nerve & aortic bodies join vagus nerve

Effects of Hydrogen Ions

• pH of CSF (most powerful respiratory stimulus)
• Respiratory acidosis (pH < 7.35) caused by failure of pulmonary ventilation
• hypercapnia (P_CO2) > 43 mmHg
• CO₂ easily crosses blood-brain barrier, in CSF the CO₂ reacts with water and releases H⁺, central chemoreceptors strongly stimulate inspiratory center
• corrected by hyperventilation, pushes reaction to the left by “blowing off ” CO₂ �CO₂ (expired) + H₂O ← H₂CO₃ ← HCO₃^- + H⁺

Effects of Hydrogen Ions

• Respiratory alkalosis (pH > 7.45)
• hypocapnia (P_CO2) < 37 mmHg
• corrected by hypoventilation, pushes reaction to the right � CO₂ + H₂O → H₂CO₃ → HCO₃^- + H⁺
• ↑ H⁺, lowers pH to normal
• pH imbalances can have metabolic causes
• diabetes mellitus: fat oxidation causes ketoacidosis, can be compensated for by Kussmaul respiration (deep rapid breathing)

Effects of CO₂ and O₂

• CO₂
• Indirect effects
• Through pH as seen previously
• Direct effects
• ↑ P_CO2 may directly stimulate peripheral chemoreceptors and trigger ↑ ventilation more quickly than central chemoreceptors
• O₂
• Usually little effect
• Chronic hypoxemia, P_O2 < 60 mmHg, can significantly stimulate ventilation
• Emphysema, pneumonia
• High altitudes after several days

Stretch and Irritants

• Stretch receptors
• Bronchi, bronchioles, and visceral pleura have stretch receptors
• Excessive stretching in pulmonary tissues inhibits I neurons via Vagus🡪DRG
• Irritants
• Sensory receptors in airways respond to irritants leading to coughing, bronchoconstriction, apnea

Negative Feedback Regulation of Breathing

• Negative feedback control of breathing
• Increase in arterial pCO2
• Stimulates receptors
• Inspiratory center
• Muscles of respiration contract more frequently & forcefully
• pCO2 Decreases

9-1 Introduction to Respiratory Physiology

Dalton’s Law

• The total pressure of a volume of gas is due to the combined partial pressures of each individual gas in the mixture.
• P_N2 + P_O2 + P_CO2 + P_H2O = 760 mmHg

Composition of Air

Henry’s Law

• Quantity of a gas that will dissolve in a liquid depends upon the amount of gas present (partial pressure) and its solubility coefficient
• explains why you can breathe compressed air while scuba diving despite 79% Nitrogen
• N₂ has very low solubility unlike CO₂ (soda cans)
• dive deep & increased pressure forces more N₂ to dissolve in the blood (nitrogen narcosis)
• decompression sickness if come back to surface too fast or stay deep too long
• Breathing O₂ under pressure dissolves more O₂ in blood

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CO₂ ~ 1.5 g/kg H₂O

O₂ ~ 0.04 g/kg H₂O

N₂ ~ 0.018 g/kg H₂O

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• Clinical application of Henry’s law
• Use of pressure to dissolve more O₂ in the blood
• treatment for patients with anaerobic bacterial infections (tetanus and gangrene)
• anaerobic bacteria die in the presence of O₂
• Hyperbaric chamber pressure raised to 3 to 4 atmospheres so that tissues absorb more O₂
• Used to treat heart disorders, carbon monoxide poisoning, cerebral edema, bone infections, gas embolisms & crush injuries

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Hyperbaric Oxygenation

Alveolar Gas Exchange

O₂ loading

CO₂ unloading

Alveolar Gas Exchange

• Time required for gases to equilibrate = 0.25 sec
• RBC transit time at rest = 0.75 sec to pass through alveolar capillary
• RBC transit time with vigorous exercise = 0.3 sec

Factors Affecting Gas Exchange

• Concentration gradients of gases
• P_O2 = 105 in alveolar air versus 40 in blood
• P_CO2 = 46 in blood arriving versus 40 in alveolar air
• Gas solubility
• CO₂ is 20 times as soluble as O₂
• O₂ has ↑ conc. gradient, CO₂ has ↑ solubility
• Membrane thickness - only 0.5 μm thick
• Membrane surface area - 100 ml blood in alveolar capillaries, spread over 70 m²
• Ventilation-perfusion coupling - areas of good ventilation need good perfusion (vasodilation)

Concentration Gradients of Gases

Ambient Pressure Affects Concentration Gradients

Lung Disease Affects Gas Exchange

↑ membrane thickness

↓ surface area

Perfusion Adjusts to �Changes in Ventilation

Ventilation Adjusts to �Changes in Perfusion

9-2 External and Internal Respiration

External Respiration

• Exchange of gas between air & blood
• Gases diffuse from areas of high partial pressure to areas of low partial pressure
• Deoxygenated blood becomes saturated
• Compare gas movements in pulmonary capillaries to tissue capillaries

Rate of Diffusion of Gases

• Depends upon partial pressure of gases in air
• P_O2 at sea level is 160 mm Hg
• 10,000 feet is 110 mm Hg / 50,000 feet is 18 mm Hg
• Large surface area of our alveoli
• Diffusion distance is very small
• Solubility & molecular weight of gases
• O₂ smaller molecule diffuses somewhat faster
• CO₂ dissolves 24X more easily in water so net outward diffusion of CO₂ is much faster

Alveolar Gas Exchange

Alveolar Gas Exchange

• Reactions are reverse of systemic gas exchange
• CO₂ unloading
• as Hb loads O₂ its affinity for H⁺ decreases, H⁺ dissociates from Hb and bind with HCO₃^-
• CO₂ + H₂O ← H₂CO₃ ← HCO₃^- + H⁺
• reverse chloride shift
• HCO₃^- diffuses back into RBC in exchange for Cl^-, free CO₂ generated diffuses into alveolus to be exhaled

Internal Respiration

• Exchange of gases between blood & tissues
• Conversion of oxygenated blood into deoxygenated
• Observe diffusion of O2 inward
• at rest 25% of available O2 enters cells
• during exercise more O2 is absorbed
• Observe diffusion of CO2 outward

Systemic Gas Exchange

9-3 Gas Transort

Adjustment to Metabolic �Needs of Tissues

• Factors affecting O₂ unloading (HbO₂ releases O₂)
• Ambient P_O2: active tissue has ↓ P_O2 , O₂ is released
• Temperature: active tissue has increased temp, O₂ is released
• Bohr effect: active tissue has ↑ CO₂, which raises H⁺ and lowers pH, O₂ is released (see following slide)
• Bisphosphoglycerate (BPG): RBC’s produce this as a metabolic intermediate, BPG binds to Hb and causes HbO₂ to release O₂
• ↑ body temp (fever), TH, GH, testosterone, and epinephrine all raise BPG and cause O₂ unloading
• Haldane effect:  CO₂ decreases affinity of Hb for O₂

Hemoglobin and Oxygen Partial Pressure

• Blood is almost fully saturated at pO2 of 60mm
• people OK at high altitudes & with some diseases
• Between 40 & 20 mm Hg, large amounts of O2 are released as in areas of need like contracting muscle

Blood O₂ Transport

• 1.34 ml O₂/g Hb
• 15 g Hb/dL blood
• 100 ml/dl blood

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• Only ~5 ml of the possible 20 ml of O₂ is delivered to tissues.

Acidity & Oxygen Affinity for Hb

• As acidity increases, O2 affinity for Hb decreases
• Bohr effect
• H+ binds to hemoglobin & alters it
• O2 left behind in needy tissues

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Carbon Monoxide Poisoning

• CO from car exhaust & tobacco smoke
• Binds to Hb heme group more successfully than O2
• CO poisoning
• Treat by administering pure O2

pCO2 & Oxygen Release

• As pCO2 rises with exercise, O2 is released more easily
• CO2 converts to carbonic acid & becomes H+ and bicarbonate ions & lowers pH.

Temperature & Oxygen Release

• As temperature increases, more O2 is released
• Metabolic activity & heat
• More BPG=more O2 released
• RBC activity
• hormones like thyroxine & growth hormone

Oxygen Affinity & Fetal Hemoglobin

• Differs from adult in structure & affinity for O2
• When pO2 is low, can carry more O2
• Maternal blood in placenta has less O2

Adjustment to Metabolic �Needs of Tissues

• Factors affecting CO₂ loading
• Haldane effect: low level of HbO₂ (as in active tissue) enables blood to transport more CO₂
• HbO₂ does not bind CO₂ as well as deoxyhemoglobin (HHb)
• HHb binds more H⁺ than HbO₂, shifts the �CO₂ + H₂O → HCO₃^- + H⁺ reaction to the right

Oxygen Imbalances

• Hypoxia
• hypoxemic hypoxia - usually due to inadequate pulmonary gas exchange
• high altitudes, drowning, aspiration, respiratory arrest, degenerative lung diseases, CO poisoning
• ischemic hypoxia - inadequate circulation
• anemic hypoxia - anemia
• histotoxic hypoxia - metabolic poison (cyanide)
• cyanosis - blueness of skin
• Primary effect of hypoxia is tissue necrosis, organs with high metabolic demands affected first

Oxygen Imbalances

• Oxygen excess
• oxygen toxicity: pure O breathed at 2.5 atm or greater
• generates free radicals and H₂O₂, destroys enzymes, damages nervous tissue, seizures, coma death
• hyperbaric oxygen
• formerly used to treat premature infants, caused retinal damage, discontinued

Obstructive �Pulmonary Diseases

• Asthma - allergen triggers histamine release, intense bronchoconstriction
• COPD’s usually associated with smoking
• chronic bronchitis
• cilia immobilized and ↓ in number, goblet cells enlarge and produce excess mucus, sputum formed (mixture of mucus and cellular debris) which is ideal growth media for bacteria, chronic infection and bronchial inflammation develops
• emphysema
• alveolar walls break down, much less respiratory membrane for gas exchange, lungs fibrotic and less elastic, air passages collapse and obstruct outflow of air, air trapped in lungs

Lung Compliance

Mechanical tethering

Other Effects of COPD

• ↓ pulmonary compliance and vital capacity
• hypoxemia, hypercapnia, respiratory acidosis
• hypoxemia stimulates erythropoietin release and leads to polycythemia
• cor pulmonale - hypertrophy and potential failure of right heart due to obstruction of pulmonary circulation

Smokers Lowered Respiratory Efficiency

• Smoker is easily “winded” with moderate exercise
• nicotine constricts terminal bronchioles
• CO in smoke binds to hemoglobin
• irritants in smoke cause excess mucus secretion
• irritants inhibit movements of cilia
• in time destroys elastic fibers in lungs & leads to emphysema
• trapping of air in alveoli & reduced gas exchange

Smoking and Lung Cancer

• Lung cancer accounts for more deaths than any other form of cancer
• most important cause is smoking (15 carcinogens)
• Squamous-cell carcinoma (most common)
• begins with transformation of bronchiolar epithelium into stratified squamous
• dividing cells invade bronchial wall, cause bleeding lesions
• dense swirls of keratin replace functional respiratory tissue

Lung Cancer

• Adenocarcinoma
• originates in mucous glands of lamina propria
• Small-cell (oat cell) carcinoma
• least common, most dangerous
• originates in primary bronchi, invades mediastinum, metastasizes quickly

Progression of Lung Cancer

• 90% of lung tumors originate in primary bronchi
• Tumor invades bronchial wall, compresses airway and may cause atelectasis
• Often first sign is coughing up blood
• Metastasis is rapid and has usually occurred by time of diagnosis
• common sites: pericardium, heart, bones, liver, lymph nodes and brain
• Prognosis poor
• 7% of patients survive 5 years after diagnosis

Healthy Lung/Smokers Lung - Carcinoma