Comprehensive Respiratory System: Functions, Mechanics, Gas Exchange, and Regulation

Four main functions of the respiratory system

Gas exchange, pH regulation, protection from pathogens, and vocalization.

What drives airflow in the respiratory system?

Pressure gradients — air moves from high to low pressure.

What creates the pressure gradients for ventilation?

The muscular pump (diaphragm and intercostal muscles).

Boyle's Law

Pressure and volume are inversely proportional; as volume ↑, pressure ↓.

Dalton's Law

The total pressure of a gas mixture = sum of partial pressures of each gas.

Partial pressure of a gas

The pressure contributed by a single gas in a mixture.

Effect of humid air on partial pressures

Water vapor "dilutes" other gases, lowering their partial pressures.

Pathway of air from atmosphere to alveoli

Nose/Mouth → Pharynx → Larynx → Trachea → Primary bronchi → Secondary → Tertiary bronchi → Bronchioles → Terminal bronchioles → Alveoli.

Function of pleural fluid

Holds lungs to thoracic wall and reduces friction during breathing.

Intrapleural pressure

Pressure in the pleural cavity — always negative to keep lungs inflated.

What happens if transpulmonary pressure equals zero?

Lungs collapse (pneumothorax).

Muscles that increase thoracic volume during inspiration

Diaphragm and external intercostals.

What happens when the diaphragm contracts?

Thoracic volume increases, pressure drops, air flows in.

What happens when the diaphragm relaxes?

Volume decreases, pressure rises, air flows out.

Connection of lung movement to the thoracic wall

The pleural fluid's surface tension.

Cells that form the alveolar walls for gas exchange

Type I alveolar cells.

Cells that produce surfactant

Type II alveolar cells.

Function of surfactant

Reduces surface tension, preventing alveolar collapse.

Why are alveoli surrounded by capillaries?

To maximize diffusion efficiency for O₂ and CO₂.

Feature allowing rapid gas diffusion in alveoli

Alveoli are one layer of simple squamous epithelium and have short diffusion distance.

Tidal volume

Air moved in/out during a normal breath (~500 mL).

Inspiratory reserve volume (IRV)

Extra air you can inhale after normal inspiration.

Expiratory reserve volume (ERV)

Extra air you can exhale after normal expiration.

Residual volume (RV)

Air left in lungs after maximal exhalation.

Vital capacity (VC)

IRV + TV + ERV — max air exhaled after deep inhale.

Compliance

The ability of lungs to stretch/expand.

Elasticity

The ability of lungs to recoil after stretching.

Central chemoreceptors

Detect CO₂ and H⁺ in cerebrospinal fluid.

What happens if CO₂ or H⁺ increase?

Ventilation increases to remove CO₂ and raise pH.

Effect of medulla suppression (e.g., opioid overdose)

Decreased somatic motor neuron signaling → reduced diaphragm contraction → respiratory depression.

Brain system affecting breathing from emotions

The limbic system.

Factors affecting airway resistance

Airway diameter, mucus, autonomic control (sympathetic = dilation, parasympathetic = constriction).

Neurotransmitter causing bronchoconstriction

Acetylcholine (ACh) via parasympathetic stimulation.

Airway resistance

Affected by airway diameter, mucus, and autonomic control (sympathetic = dilation, parasympathetic = constriction).

Acetylcholine (ACh)

Neurotransmitter that causes bronchoconstriction via parasympathetic stimulation.

Histamine

Powerful bronchoconstrictor released by mast cells.

Epinephrine

Drug that reverses bronchoconstriction during allergic reactions.

Concentration gradient

Most variable factor influencing gas diffusion.

Diffusion rate factors

Surface area × gradient × membrane permeability / distance.

Low alveolar PO₂

Results in decreased O₂ diffusion into blood, leading to hypoxia.

Causes of low alveolar PO₂

Low inspired O₂ (high altitude) or hypoventilation (poor airflow).

Hypoxic hypoxia

Occurs at high altitude due to low arterial PO₂.

Anemic hypoxia

Caused by low hemoglobin or hemoglobin malfunction.

Ischemic hypoxia

Results from reduced blood flow.

Histotoxic hypoxia

Occurs when cells are poisoned and cannot use O₂ (e.g., cyanide).

Adult Respiratory Distress Syndrome (ARDS)

Fluid in alveoli causing refractory hypoxia not fixed by O₂ therapy.

Oxygen transport in blood

~98% bound to hemoglobin (HbO₂), ~2% dissolved in plasma.

Hemoglobin binding capacity

One hemoglobin molecule can bind four O₂ (one per heme group).

Factors increasing oxygen unloading

Low pH, high temperature, high PCO₂, high 2,3-BPG (right shift of curve).

Bohr effect

Decreased pH (↑H⁺) leads to reduced O₂ affinity and more O₂ released to tissues.

Effect of increased pH

The curve shifts left, meaning less O₂ is released (higher affinity).

CO₂ transport in blood

70% as bicarbonate (HCO₃⁻), 23% bound to hemoglobin (carbaminohemoglobin), 7% dissolved in plasma.

Carbonic anhydrase

Enzyme that converts CO₂ ↔ HCO₃⁻ + H⁺ in red blood cells.

Effect of increased blood CO₂

pH drops (more acidic) leading to increased ventilation.

Solubility comparison

CO₂ is approximately 20× more soluble in water than O₂.

Increasing O₂ dissolution

To dissolve as much O₂ as CO₂, increase the partial pressure of oxygen.

Pulmonary fibrosis

Disease with low compliance, making it hard to expand lungs.

Emphysema

Disease with low elastance, making it hard to recoil lungs.

Restrictive lung disease example

Pulmonary fibrosis — lungs stiff and resist inflation.

Obstructive lung disease example

Asthma or COPD — airways narrowed, airflow limited.

Hypercapnia

Condition where CO₂ levels rise, leading to increased ventilation to expel CO₂ and normalize pH.

Effect of increased alveolar ventilation

PO₂ rises, PCO₂ drops.

Normal breathing rate

About ~20 breaths/min (based on 5 breaths in 15 seconds).

Apnea

Cessation of breathing.

Dyspnea

Difficult or labored breathing.

Tachypnea

Rapid shallow breathing.

Hyperpnea

Increased breathing rate/depth due to metabolism (e.g., exercise).

Hyperventilation

Breathing faster than metabolic need, causing CO₂ drop and alkalosis.

Exhaled CO₂ after breath hold

Increases due to CO₂ buildup.

Effect of increased breathing rate on exhaled CO₂

Decreases as CO₂ is blown off.

Epinephrine effect on bronchioles

Dilates them, improving airflow.

CFTR channel malfunction

Leads to failed chloride transport, thick mucus, and airway blockage (cystic fibrosis).