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Chapter 14. Respiratory System

Higher category: 【Biology】 Biology Index 

1. Overview of breathing

2. Lung structure (mammals)

3. Lung ventilation (mammals)

4. Gas transport of blood

5. Control of breathing

6. Acidosis and alkalosis

7. Lung disease

1. Overview of Breathing

⑴ Stage of breathing

① Exhalation: Gas exchange between the atmosphere and the respiratory tract (ventilation)

② Diffusion: Gas exchange between respiratory tract and blood

③ Mass transport: Carrying of blood

④ Breathing: Gas exchange between blood and tissue cells

⑤ Cell respiration: Receives O₂ to oxidize organic matter and produces CO₂ and ATP

⑵ Respiration in Insect: Delivers air directly through a system of tracheae only.

① Airflow Pathway: Trachea → Tracheoles → Air Capillaries

○ 1^st. Atmospheric oxygen enters the trachea (the largest air tube) through spiracles located on the sides of the abdomen.

○ 2^nd. The inhaled air moves into the tracheoles, which are narrow tubes closed at one end, branching from the trachea.

○ 3^rd. Near tissues with high oxygen demand, there are expanded sections of tracheoles that act as air sacs.

○ 4^th. Oxygen in the tracheoles diffuses into the air capillaries.

② The structure of the trachea is supported by ring-shaped chitin.

③ The ends of the tracheoles are filled with a dark bluish liquid. When activity increases and oxygen consumption rises, most of this liquid is absorbed into the body fluid, increasing the air-filled volume of the tracheoles.

④ Aquatic insects use air bubbles for oxygen intake while submerged.

⑶ Respiration in Fish: Use of Gills as Respiratory Organs

① Located on both sides of the fish.

② Each side contains four gill arches situated between the mouth and the operculum, which serve as structural supports.

③ Each gill arch bears hundreds of gill filaments, and lamellae are arranged above and below these filaments.

○ Lamellae: The actual surface for gas exchange.

④ Blood vessels passing through the gills: afferent vessels and efferent vessels.

○ Afferent vessels: Carry blood to the gills.

○ Efferent vessels: Carry blood away from the gills.

⑤ Gas exchange efficiency is enhanced through ventilation and countercurrent exchange.

○ Countercurrent exchange: The flow of blood inside the lamellae is in the opposite direction to the flow of water over them.

⑷ Respiration in Amphibians

① During the larval stage, amphibians use gills; as adults, they use lungs for respiration.

○ Reptiles, birds, and mammals all rely on lungs for breathing.

② Amphibians ventilate their lungs using positive-pressure breathing.

○ Positive-pressure breathing: A breathing mechanism in which air is pushed into the lungs by increasing pressure near the respiratory surface, allowing oxygen to dissolve into the capillaries passing through it.

○ This involves a “gulping” or swallowing motion to force air into the lungs.

○ Negative-pressure breathing: A mechanism that lowers the pressure near the respiratory surface, drawing air in so that oxygen can diffuse into the surrounding capillaries.

○ Example: Mammals.

③ Cutaneous respiration: About 50% of gas exchange occurs through the skin.

⑸ Respiration in Birds

① Air sacs: Air-filled spaces located in the lungs and some bones.

② Airflow pathway: Trachea → Bronchi → Secondary bronchi → Air capillaries → Involves two inhalations and two exhalations for a single breath cycle.

○ Posterior air sacs → Lungs → Anterior air sacs

○ 1^st Inhalation: Air enters and fills the posterior air sacs.

○ 1^st Exhalation: Posterior air sacs contract, pushing air into the lungs.

○ 2^nd Inhalation: Air moves from the lungs into the anterior air sacs.

○ 2^nd Exhalation: Anterior air sacs contract, expelling the air taken in during the first inhalation.

③ Advantages of avian respiration:

○ The bird lung is not dead-ended, meaning no residual volume remains after exhalation, leading to high gas exchange efficiency.

○ Birds have less expansion and contraction of the lungs compared to mammals.

⑹ Respiration in Mammals

2. Lung structure (mammals)

⑴ Airflow: Mouth or nose → Nasal cavity → Pharynx → Larynx → Trachea → Bronchi → Bronchioles → Alveoli

① Air is filtered, warmed, and humidified as it passes through the nasal cavity.

② Air entering through the nasal cavity moves to the pharynx (the junction of the esophagus and larynx), where it also meets food that enters through the mouth.

③ Palatal reflex

○ When swallowing food

○ Epiglottis: directs food to the esophagus and air to the trachea.

○ 1^st: The larynx moves upward, and the epiglottis closes the glottis (entrance of the airway).

○ 2^nd: Food passes down the esophagus and reaches the stomach.

○ During the remaining time: the airway stays open for breathing.

○ Foreign particles trapped in goblet cell mucus are directed into the esophagus.

○ Goblet cells: secrete mucus to protect the mucous membrane.

④ Vocal cords

○ The walls of the larynx and trachea (which act as vocal cords) are reinforced with cartilage to keep the airway open.

○ Voluntary vocal muscles: strong contraction produces high-pitched sounds; weak contraction produces low-pitched sounds.

⑤ Bronchi (two main branches): the epithelial cells lining the primary bronchi use cilia and mucus to push foreign substances into the esophagus.

⑵ Anatomical Structure of the Lungs

① The lungs consist of light, spongy tissue, mostly filled with air spaces.

② Each lung is enclosed in a pleural sac, preventing gas exchange with the thoracic cavity.

③ Lobes: the right lung has three lobes, the left lung has two lobes.

○ Right lung: superior lobe (26.53%), middle lobe (4.08%), lower lobe (18.37%)

○ Left lung: superior lobe (28.57%), lower lobe (22.45%)

⑶ Alveoli

① About 400 million in number, single-layer epithelium, diameter 0.1–0.3 mm.

② Alveolar-capillary distance: 0.1–1.5 μm, allowing extremely efficient diffusion.

③ Special alveolar structure creates lung elasticity:

○ Alveoli contain no muscle (to avoid interfering with gas exchange), but connective tissue is rich in elastin, allowing contraction and relaxation.

○ Elastin fibers: provide elasticity opposing tension.

○ Surface tension: thin water layer covering alveoli pulls inward, creating strong contractile force.

④ Types of alveolar cells:

○ Type I alveolar cells (AT1): most abundant epithelial cells, more numerous than AT2.

○ Type II alveolar cells (AT2): secrete surfactant on villous surfaces, preventing alveolar collapse caused by water surface tension.

○ Laplace pressure in a bubble: P = 2T / r

○ Smaller AT2 cells secrete more surfactant to counter higher surface tension.

○ Surfactant: complex of lipids, proteins, and carbohydrates; main component is DPPC (dipalmitoyl phosphatidylcholine).

○ Neonatal Respiratory Distress Syndrome (NRDS): second leading cause of infant mortality; caused by immature AT2 cells producing insufficient surfactant.

○ Macrophages: remove foreign substances.

⑤ Total alveoli: about 8 × 10⁶, providing a respiratory epithelial surface area of 50–100 m².

○ By comparison, body surface area is ~2 m².

⑷ Functional Structure of the Lungs

① Lung blood volume: 0.5 L (10–12% of total blood).

② Lung volume: 3 L.

③ In mammals and fish, larger body mass correlates with greater respiratory surface area.

④ Oxygen uptake in mammals is proportional to alveolar surface area.

⑤ Obesity: reduced respiratory surface area → limited oxygen supply → decreased activity.

3. Lung ventilation (mammals)

⑴ Breathing pressure: Consumes 3-5% of total energy

① The lungs are passively ventilated with diaphragm and intercostal contractions connected to the pleura

○ The lungs themselves have no muscles and cannot actively contract

○ Thoracic cavity: The lungs are floating in the chest cavity and the chest cavity is a closed space

○ Pleura: Comprised of proximal and pleural pleura, pleural effusion in interstitial space (3-4 mL)

○ Pneumothorax: Perforation of the pleura due to infection or cuts

○ Gang: Thin space surrounding the lungs

○ Contractions of the diaphragm and intercostal muscles are transmitted to the lungs through the pleural effusion so that the lungs are passive contractions

○ Lung flexibility: More surfactant, less scar tissue increases lung flexibility

② Inspiration (Inhalation): Rib rise (external intercostal contraction), diaphragm descend (diaphragm contraction) → thoracic expansion → pressure drop → air inflow

③ Exhalation: Rib lowering (intercostal contraction), diaphragm rise (diaphragm relaxation) → thoracic contraction → pressure rise → air release

○ Less consumption of ATP during the exhalation process due to gravity and lung elasticity

④ Alveolar pressure, intrathoracic pressure change during breathing

○ Point 1. The pleural intraluminal pressure should be less than the alveolar pressure because the human body regulates the pleural cavity pressure to control the alveolar pressure

○ Point 2. The lungs show a wave graph because the air flows in when the pressure is lowered to offset the change.

○ Volumetric-pressure curve of the lung (link: / 1464): When inflating requires more pressure than when contracting

⑤ Disadvantages: Partial Pressure Slope Reduction, Backflow Gas Exchange ×

○ Due to the large amount of oxygen in the atmosphere, the disadvantages do not significantly affect species survival

⑵ Spirometry curve

① Parameter

○ Inspiratory residual volume

○ Expiratory residual volume

○ Residual volume

○ Spirometry = 1 tidal volume + absorbent reserve + phagocytic reserve

○ Total lung volume = 1 breath volume + absorbent reserve amount + eosinophilic reserve amount + residue amount

○ Intake volume = tidal volume + absorbent reserve

○ Functional residue amount = phagocytic reserve amount + residue amount

② Gas exchange at rest

○ Tidal volume: 500 mL

○ Ventilation rate: Respiratory Rate Per Minute. Typically 8-12 times per minute

○ Total waste ventilation: Ventilation rate × tidal volume = 8 × 500 mL / min to 12 × 500 mL / min = 3 to 6 L / min

○ Inspiration: Nitrogen 78%, Oxygen 21%, Carbon Dioxide 0.3%

○ Exhalation: Nitrogen 78%, Oxygen 17%, Carbon Dioxide 4%

○ 250 mL O² / min influx into the blood → 360 to 600 L / day O²

○ 200 mL CO² / min discharge into the lungs

○ Alveolar ventilation increased more than 20 times during exercise, alveoli blood flow increased 5-6 times

③ Dead space

○ Amount that does not contribute to gas exchange at one breath

○ Cause: Trachea from trachea to bronchioles lack respiratory epithelium and fail to participate in gas exchange

○ Degree: The anatomical dead space is about 140 mL, but the physiological dead space is about 150 mL, given that the bronchial dilated upon inspiration.

○ Alveolar ventilation volume (the amount of air reaching the alveoli) = ventilation rate (breath rate per minute) × (1 breath volume-dead space)

④ Ventilation volume and partial pressure of gas in the alveoli

○ Acidosis, Alkalosis General (See. 6)

○ Ventilation volume ↑ → CO2 release ↑ → respiratory alkalosis

○ Ventilation volume ↓ → CO2 in plasma ↑ → respiratory acidosis

⑶ Transpulmonary Pressure-Volume Graph

① Compliance 

○ The degree to which the volume changes with pressure change

○ More surfactant increases the extension

② Inspiration: Confrontation between force to inflate alveoli and surface tension

○ Graphs that don’t seem to increase in volume

○ When treating surfactant: Reduced surface tension → Easy alveolar expansion → Moving graph in the direction of increasing volume

③ Exhalation: Strength of alveoli and surface tension strengthen each other

○ A graph that seems to increase in volume

○ When treating surfactant: Decrease in surface tension → negative alveolar contraction → move graph in the direction of increasing volume

4. Gas transport of blood

⑴ Breathing pigment: Special proteins that carry oxygen

① Hemocyanin: Breathing pigments of arthropods and molluscs, blue (including Cu)

② Hemoglobin: Breathing pigments of most vertebrates and invertebrates, red (including Fe)

③ Myoglobin: More oxygen affinity than hemoglobin, red (including Fe)

○ Diving mammals, heart and muscles are high in myoglobin

○ Myoglobin cannot enter the blood

⑵ Oxygen transport

① Function of hemoglobin: Oxygen transport

○ One red blood cell contains 250 million Hb → carries 1 billion molecules of oxygen (99%)

○ 198 mL / L of 200 mL / L of total blood oxygen

○ Less than 1% oxygen dissolved in plasma or red blood cell substrate

○ Respiratory pigment has higher saturation with higher oxygen partial pressure

○ Hemoglobin binds to oxygen in the lungs (100% saturation) and dissociates only about 30 to 40% at the tissue ends

② Structure: Allosteric enzyme, α2 β2 (quaternary structure, HbA), each unit consisting of heme and globin

○ Myoglobin only consists of tertiary structure

○ Heme: It has an organic ring structure called porphyrin, with Fe2+ in the center

○ Fetus: HbF (Hb Fetus) is present

○ Embryo ~ 8 weeks: ζ2 ε2 

○ About 6 weeks pregnant, HbF begins to be produced in the liver

○ Around 8 months of pregnancy, HbA begins to form in the bone marrow

○ In newborns, 70% are HbF and 30% are HbA

○ Rapid HbA (Hb Adult) replacement between 3 and 6 months after birth (HbF destruction)

○ Oxygen affinity: α2 γ2 > α2 β2

○ Oxygen released from maternal hemoglobin binds to fetal hemoglobin

○ Cause: BPG binding site sequence difference, γ chain of HbF and β chain of HbA differ about 38% in amino acid sequence

○ BPG affinity: γ chain β chain (See. 4-⑶-④)

○ HbA₂: About 2% of hemoglobin in adults (98% is HbA), α₂δ₂

○ See: Hemocyanin is a respiratory pigment with copper, not iron, found in arthropods and molluscs a lot.

③ Ligands that bind to Hb’s heme (competitive inhibition of oxygen)

○ oxy Hb: Hb + O₂ → HbO₂(red)

○ saturated oxy HB: Hb + 4O₂ → Hb(O₂)₄

○ reduced Hb: Hb + H⁺ → HHb (reddish brown)

○ met Hb: OH^- (Fe³⁺) occurs occasionally, but resolves itself in vivo

○ carboxy Hb: CO (affinity ) causes carbon monoxide poisoning

○ cyano Hb: Causes of death of CN^- (affinity ) and cyanide (KCN)

○ (Note) Carbon dioxide and 2,3-BPG bind to globin and do not act as an inhibitor, but lower red blood cell oxygen transport ability.

④ Cooperative: In the fourth structure, when the substrate is bound to one monomer, the affinity of the substrate of the surrounding monomer increases.

○ Myoglobin forms the shape (MM type) expected by the Michaelis-Menten equation because of the constant affinity of the substrate.

○ Myoglobin is not an allosteric protein such as hemoglobin

○ Myoglobin has higher oxygen affinity than hemoglobin, so oxygen storage at low oxygen partial pressure; The presence of multiple myocytes

○ Seals, which are submersible mammals, store about twice as much oxygen per kilogram of body weight as myoglobin ↑.

○ Hemoglobin shows the sigmoid type (S-shape) because the affinity of the substrate is gradually increased

○ Hemoglobin is an allosteric protein to which two or more ligands can bind

○ Even if only one oxygen molecule is bound to hemoglobin, the subunit becomes a structure with high affinity with oxygen

○ Conversely, only one oxygen molecule escapes from saturated hemoglobin, resulting in a low oxygen affinity.

○ Stability: Oxygen carrying capacity is greatly reduced even when the partial pressure of oxygen in alveoli and arterial blood reaches 100 mmHg to 60 mmHg ×

⑶ Bore effect: Oxygen Affinity Change of Hemoglobin by Four Factors (pH, pCO2, Temperature, 2,3-BPG)

① H⁺ effect

○ [H⁺] ↑ → pH ↓ → Changes in ionic bonds in Hb (eg histidine of β chain) → Hb conformation change → oxygen affinity ↓

○ Oxygen and dissociated hemoglobin combine with hydrogen ions to prevent acidification of blood

○ Ion Bond Change 1: -COOH ↔ -COO- + H⁺ (Place: Globin)

○ Ion Bond Change 2: -NH2 + H+ ↔ -NH3+ (Location: Globin)

○ Oxygen affinity change during exercise 1: PH ↓ → oxygen affinity ↓ due to lactic acid and fatty acid production

② CO₂ effect

○ CO₂ ↑ → CO₂ binding or acid increase at N-terminus → Hb conformational change → oxygen affinity ↓

○ CO_{2 bonding at the N-terminus} 

○ Acid increase: If pCO₂ is high, pH is reduced to H + derived from carbonic acid.

○ Reduced oxygen affinity allows hemoglobin to dissociate oxygen better in tissue cells

③ Temperature effect

○ Temperature ↑ → Hb conformation change → Oxygen affinity ↓

○ Actively metabolizing or exercising cells release heat

○ Enzymes rapidly lose their activity as their intramolecular bonds weaken at temperatures after their activation temperature

④ 2,3-BPG (2,3-bisphosphoglycerate) effect

○ 2,3-BPG: Active production of glycolysis, isomer of 1,3-BPG, an intermediate product of glycolysis

○ Mammalian erythrocytes have high concentrations of 2,3-BPG

○ 2,3-BPG ↑ → Stabilizes deoxyhemoglobin by combining with β globin in the middle of hemoglobin → additional oxygen affinity ↓

○ Oxygen affinity change during exercise 2: Tissue cell oxygen debt phenomenon → Some G3Ps convert to 2,3-BPG → Oxygen bond in β globin ↓

⑤ When moving to a high altitude mountain

○ 1^st. Reduction of partial pressure of oxygen in the atmosphere

○ 2^nd. Decreases the amount of oxygen binding of hemoglobin in the lungs

○ Increase respiratory rate to compensate for insufficient oxygen binding

○ Respiratory algorithm: Increasing respiratory rate releases excess CO2, increasing blood pH

○ 3^rd. Decreased oxygen supply to tissue cells → Increased 2,3-BPG in red blood cells

○ Reduced oxygen affinity of hemoglobin releases more oxygen from oxygen hemoglobin

○ 4^th. Reduced oxygen supply to the kidneys

○ 4^th-1^st. Increased erythropoietin secretion in the kidneys

○ 4^th-2^nd. Promote red blood cell production in bone marrow → increase red blood cell count

⑷ Carbon dioxide transport

① Plasma: 8%, simple diffusion (melting)

○ CO₂ (g) → CO₂ (aq)

② Combined with hemoglobin: HbCO₂, about 22%

③ Bicarbonate ion: HCO₃^-, about 70%

○ 1^st. CO₂ (aq) simply diffuses from plasma to red blood cells

○ 2^nd. Promoted by CO₂ (aq) + H₂O (l) → H₂CO₃ (aq), carbonic anhydrase (CA)

○ 3^rd. H₂CO₃ → H+ + HCO₃^-

○ 4^th. H⁺ combines with Hb to become HHb (See. ⑶-①)

○ 5^th. HCO₃^- is one-to-one reverse cotransport with Cl^- and discharged out of plasma

○ 6^th. Osmotic pressure causes water to enter as Cl^- increases in erythrocytes → volume increases

⑸ Pulmonary and body circulation: Circulation and respiratory system harmony

① Pulmonary Circulation (12% Blood Retention)

○ Right ventricle → Pulmonary artery → Pulmonary capillary → Pulmonary vein → Left atrium

○ Blood with O₂↓, CO₂↑ → Blood with O₂↑, CO₂↓

② Circulation (79% blood retention)

○ Left ventricle → aorta → artery → capillary → vein → vena cava → right atrium

○ Blood with O₂↑, CO₂↓ → Blood with O₂↓, CO_2</sub↑

○ Aortic partial pressure: 80 to 100 mmHg

○ Venous oxygen partial pressure: 40 mmHg

○ Supply nutrients and oxygen to tissue cells

5. Control of breathing

⑴ Control of number: Cortex → Cortex spinal cord → Motor neurons

⑵ Self-regulating central: Pontoon, training → voluntary, rhythmic activity

① Soft water: Basic breathing control

○ Soft water is more affected by carbon dioxide than oxygen

② Pons: Adjusts for smooth transition between inspiration and exhalation, breathing rate

③ Input and receiver

○ Chemical receptors in the central nervous system (especially cerebrospinal fluid) (pO₂, pCO₂, H⁺)

○ H⁺ cannot cross the brain-vascular barrier so chemical receptors determine H⁺ by the amount of CO₂

○ Increase metabolism through exercise → CO₂ ↑ → Increase respiration → Excessive CO₂ emissions → Normalize pH

○ Input of chemical receptors (H⁺, pO₂, pCO₂) of aortic bodies (next to the aortic arch) and carotid bodies (next to the carotid artery)

○ O₂ concentration does not have a significant effect on breathing, but increases respiration rate when O₂ levels are low

○ Plasma epinephrine and potassium concentration receptors

○ Muscle and joint kidney receptor input

○ Renal Receptor Input to Lung

○ Stimulation (temperature, etc.) input through other receptors and under Thalamus

④ Breathing control process

○ Breathing exercise: Sympathetic stimulation, adrenaline secretion

○ Respiratory movement suppression: Parasympathetic stimulation, acetylcholine secretion

6. Acidosis and alkalosis

⑴ Steady state

① PH: 7.41 to 7.45

② O₂: 40 mmHg (tissue) or more 100 mmHg (lung) or less

③ CO₂: 40 mmHg (lung) or more 46 mmHg (tissue) or less

④ HCO₃^-: 24 mmEqmol

⑵ Acidosis and Alkalosis

① Acidosis: pH 7.35 or less

② Alkalosis: pH 7.45 or more

⑶ Metabolic alkalosis: Metabolism Excessive HCO3-

① Excess HCO₃^- reacts with H⁺ resulting in high pH

② Compensation: Increased partial pressure of CO₂ by lowering breathing rate to lower pH

③ Example: Vomiting (exhaust acid from the stomach)

⑷ Metabolic acidosis: If HCO₃^- is low due to metabolism

① Less HCO₃sup>-</sup>, H⁺ remains in the blood, resulting in lower pH

② Compensation: Lowers CO₂ partial pressure by increasing respiration rate to increase pH

③ Example: Diarrhea (Bicarbonate Release)

⑸ Respiratory alkalosis: When the partial pressure of CO2 is lowered in relation to breathing

① Lower CO₂ partial pressure results in higher blood pH

② Compensation: Suppresses HCO₃^-reaction to lower pH

③ Example: Hyperventilation, limited lung disease (e.g., Pulmonary fibrosis)

⑹ Respiratory acidosis: High CO₂ partial pressure associated with respiration

① Low CO₂ pH due to no CO₂ emissions

② Compensation: Activate HCO₃<sup-</sup> reaction to increase pH

③ Example: Obstructive pulmonary disease (e.g., asthma)

7. Lung disease

⑴ Acidosis and Alkalosis

① Normal Conditions

○ pH: 7.41 ~ 7.45

○ O₂: ≥ 40 mmHg (tissue), ≤ 100 mmHg (lungs)

○ CO₂: ≥ 40 mmHg (lungs), ≤ 46 mmHg (tissue)

○ HCO₃^-: 24 mEq/mol

② Acidosis and Alkalosis

○ Acidosis: When pH is below 7.35

○ Alkalosis: When pH is above 7.45

Figure 10. Acidosis and Alkalosis

③ Metabolic Alkalosis: Caused by excessive HCO₃^- due to metabolism

○ Excess HCO₃^- binds to H⁺, raising the pH

○ Compensation: Decreased respiratory rate to raise CO₂ partial pressure and lower pH

○ Example: Vomiting (loss of acidic gastric content)

④ Metabolic Acidosis**: Caused by depletion of HCO₃^- due to metabolism

○ Reduced HCO₃^- leaves more free H⁺ in blood, lowering pH

○ Compensation: Increased respiratory rate to reduce CO₂ partial pressure and raise pH

○ Example: Diarrhea (loss of bicarbonate from the body)

⑤ Respiratory Alkalosis**: Caused by reduced CO₂ partial pressure due to respiration

○ Lower CO₂ leads to elevated blood pH

○ Compensation: Inhibition of HCO₃^- production to lower pH

○ Example: Hyperventilation, restrictive lung diseases (e.g., pulmonary fibrosis)

○ Narrowing of blood vessels including cerebral vessels may occur to prevent CO₂ loss, causing dizziness

○ Treatment for hyperventilation: Breathing into a paper bag to rebreathe exhaled CO₂

⑥ Respiratory Acidosis: Caused by increased CO₂ partial pressure due to impaired respiration

○ Retention of CO₂ lowers blood pH

○ Compensation: Activation of HCO₃^- production to raise pH

○ Example: Obstructive lung diseases (e.g., asthma)

⑵ Lung Cancer

① Type 1. SCLC (Small Cell Lung Cancer): Accounts for 15% of all lung cancers.

○ Chemotherapy and radiation therapy are the primary treatments

○ Originates from neuroendocrine cells

○ Most cases are associated with heavy smoking

○ Surgery is rarely performed, so research samples are relatively limited

② Type 2. NSCLC (Non-Small Cell Lung Cancer): Accounts for 85% of all lung cancers.

○ Surgery is the primary treatment; chemotherapy and radiation are secondary

○ 2-1. LUSC (Lung Squamous Cell Carcinoma): 45% of all lung cancers

○ Smoke-driven

○ Involves KRAS

○ Originates from basal epithelial cells

○ 2-2. LUAD (Lung Adenocarcinoma): 45% of all lung cancers

○ EGFR mutation-driven

○ Combination therapy with immune checkpoint inhibitors (ICI) is being explored

○ Originates from alveolar type II epithelial cells

○ 2-3. LCC (Large-Cell Carcinoma): Originates from various epithelial cells

③ Lung Cancer and Smoking

○ Tar and fine particles remain on lung surfaces, causing mutations and cancer

○ Characteristics of cigarettes:

○ Contain around 100,000 chemicals

○ About 20 classified as Group A carcinogens

○ Major harmful substances: tar, carbon monoxide, nicotine

○ Tar: Cigarette residue, ~10 mg per cigarette

○ Contains ~40 carcinogens

○ Penetrates the bloodstream and destroys cells

○ Disrupts immune system, induces chronic inflammation

○ Damages cilia and elastin

○ Carbon Monoxide:

○ Product of incomplete combustion

○ Most abundant substance in cigarette smoke

○ Main cause of chronic hypoxia, premature aging, and atherosclerosis

○ Nicotine: ~0.1 to 0.6 mg per cigarette

○ Reaches the brain in ~7 seconds

○ Addictive, narcotic, toxic; also used in pesticides and herbicides

○ Increases blood pressure

○ Other toxic substances:

○ Benzo[a]pyrene: Carcinogen

○ Dimethylnitrosamine: Carcinogen

○ Hydrogen cyanide: Lethal gas chamber toxin

○ Naphthylamine: Preservative

○ Naphthalene: Moth repellent

○ DDT: Pesticide

⑶ Chronic Obstructive Pulmonary Disease (COPD)

① Symptoms: Increased mucus and narrowed airways (due to elastin dysfunction) increase airway resistance and cause ventilation impairment

② Feature 1: Total lung capacity and residual volume are higher than normal (compensatory)

③ Feature 2: Respiratory function is always lower than normal

④ Rolipram: A clinical drug used to treat COPD

⑤ Example 1. Chronic Bronchitis:

○ Excessive mucus secretion in bronchi → chronic inflammation in lower airways

⑥ Example 2. Asthma:

○ Causes: Allergic reactions, viral infections, etc.

○ Symptoms: Alveolar constriction, increased mucus secretion, increased airway resistance, chronic inflammation

○ Fine particles exacerbate asthma

⑦ Example 3. Emphysema:

○ Caused by scar tissue formation due to bronchitis and asthma

○ Destruction and blockage of small airways → reduced alveoli count and surface area

○ Irreversible

⑷ Restrictive Lung Diseases

① Symptoms: Reduced lung compliance (ability to expand), leading to ventilation impairment

② Feature 1: Total lung capacity and residual volume are lower than normal

③ Feature 2: Respiratory function is comparable to normal within a limited range

④ Example 1. Pulmonary Fibrosis

○ Subtypes:

○ IPF (Idiopathic Pulmonary Fibrosis)

○ cHP (Chronic Hypersensitivity Pneumonitis)

○ NSIP (Nonspecific Interstitial Pneumonia)

○ Sarcoidosis

○ Unclassifiable ILD

○ Consolidation: Lung appears completely white

○ Crazy paving: Thickened blood vessels

○ Treatment: Nintedanib, Pirfenidone (target tyrosine kinases)

⑤ Example 2. Pneumoconiosis, Tuberculosis

⑥ Example 3. Occupational Lung Disease

○ Fine dust (asbestos, coal dust, silica, paper dust, pollen, etc.) accumulates in macrophages

○ Scar tissue replaces lung tissue → fibrous cysts, reduced lung flexibility

⑸ Pulmonary Edema

① Definition: A condition in which fluid leaks into alveoli as pulmonary veins exceed lymphatic drainage capacity

○ Lymphatic drainage: Ability to recover interstitial and lymph fluid from pulmonary capillaries

② Causes**:

○ Heart failure → increased pulmonary venous pressure

○ Decrease in external air pressure

③ Symptoms: Causes shortness of breath

⑹ ARDS (Acute Respiratory Distress Syndrome)

① Example: Post-SARS-CoV-2 lung disease

Input: 2015.7.19 11:19