- Occurs in five stages
- Initial development includes development of lung bud from distal end of respiratory diverticulum during week 4.
- Lung bud → trachea → bronchial buds → mainstem bronchi → secondary (lobar) bronchi → tertiary (segmental) bronchi.
- NOTE: Errors at this stage can lead to tracheoesophageal fistula.
- Endodermal tubules → terminal bronchioles. Surrounded by modest capillary network.
- NOTE: Respiration impossible, incompatible with life.
- Terminal bronchioles → respiratory bronchioles → alveolar ducts. Surrounded by prominent capillary network.
- Pneumocytes develop starting at 20 weeks
- NOTE: Airways increase in diameter. Respiration capable at 25 weeks.
- Alveolar ducts → terminal sacs. Terminal sacs separated by 1° septae.
- Terminal sacs → adult alveoli (due to 2° septation).
- In utero, “breathing” occurs via aspiration and expulsion of amniotic fluid → ↑ vascular resistance through gestation.
- At birth, fluid gets replaced with air → ↓ in pulmonary vascular resistance.
- NOTE: At birth: 20–70 million alveoli.
- By 8 years: 300–400 million alveoli.
Congenital lung malformations
- Poorly developed bronchial tree with abnormal histology.
- Associated with congenital diaphragmatic hernia (usually left-sided) and bilateral renal agenesis (Potter sequence).
- Caused by abnormal budding of the foregut and dilation of terminal or large bronchi.
- Discrete, round, sharply defined, fluid-filled densities on CXR (air-filled if infected)
- Generally asymptomatic but can drain poorly, causing airway compression and/or recurrent respiratory infections.
- Usually found in mediastinum
- Diagnostic criteria: Walls contain cartilage
Club cells and Alveolar cell types
- Nonciliated; low-columnar/cuboidal with secretory granules.
- Located in small airways.
- Secrete component of surfactant
- Degrade toxins
- Act as reserve cells
- Collapsing pressure (P) = 2 (surface tension) / radius
- Alveoli have increased tendency to collapse on expiration as radius decreases (law of Laplace).
- Pulmonary surfactant is a complex mix of lecithins, the most important of which is dipalmitoylphosphatidylcholine (DPPC).
- Surfactant synthesis begins around week 20 of gestation, but mature levels are not achieved until around week 35.
- Corticosteroids important for fetus surfactant production and lung development.
- 97% of alveolar surfaces.
- Line the alveoli
- Squamous; thin for optimal gas diffusion.
- Secrete surfactant from lamellar bodies (arrow in image) leads to decreased alveolar surface tension, prevents alveolar collapse, decreased lung recoil, and increased compliance.
- Cuboidal and clustered (image)
- Also serve as precursors to type I cells and other type II cells.
- Proliferate during lung damage, regenerating the alveolar lining after injury.
- Phagocytose foreign materials, release cytokines and alveolar proteases.
- Hemosiderin-laden macrophages may be found in the setting of pulmonary edema or alveolar hemorrhage.
Neonatal Respiratory Distress Syndrome
- Fetal Lung Immaturity
- Lack of Surfactant
- Respiratory Distress
- Nasal Flaring
- Mechanical Ventilation
- Total Parenteral Nutrition (TPN)
Screening tests for fetal lung maturity
- Lecithinsphingomyelin (L/S) ratio in amniotic fluid (≥ 2 is healthy; < 1.5 predictive of NRDS)
- Foam stability index test
- Surfactant-albumin ratio.
- Persistently low O2 tension leads to risk of PDA.
- Preterm delivery: betamethasone used to stimulate surfactant production in lungs
- Preterm delivery: betamethasone used to stimulate surfactant production in lungs
- Large airways consist of nose, pharynx, larynx, trachea, and bronchi.
- Small airways consist of bronchioles that further divide into terminal bronchioles (large numbers in parallel resulting in the least airway resistance).
- Warms, humidifies, and filters air but does not participate in gas exchange, known as “anatomic dead space.”
- Cartilage and goblet cells extend to end of bronchi.
- Pseudostratified ciliated columnar cells primarily make up epithelium of bronchus and extend to beginning of terminal bronchioles, then transition to cuboidal cells.
- Clear mucus and debris from lungs (mucociliary escalator).
- Airway smooth muscle cells extend to end of terminal bronchioles (sparse beyond this point).
- Lung parenchyma; consists of respiratory bronchioles, alveolar ducts, and alveoli.
- Participates in gas exchange.
- Mostly cuboidal cells in respiratory bronchioles, then simple squamous cells up to alveoli.
- Cilia terminate in respiratory bronchioles.
- Alveolar macrophages clear debris and participate in immune response.
- Right lung has 3 lobes; Left has Less Lobes (2) and Lingula (homolog of right middle lobe).
- Instead of a middle lobe, left lung has a space occupied by the heart
- Relation of the pulmonary artery to the bronchus at each lung hilum is described by RALS—Right Anterior; Left Superior.
- Carina is posterior to ascending aorta and anteromedial to descending aorta (IMAGE)
- Right lung is a more common site for inhaled foreign bodies because right main stem bronchus is wider, more vertical, and shorter than the left.
- Horizonal fissure is located near the 4th rib
- Needle positioning for tension pneumothorax is between 2nd - 3rd rib
- Arteries run with the airways at the center of the bronchopulmonary segments
- While upright—enters basal segments of right lower lobe. Preferentially on right, but bilateral basal segments can be involved.
- While supine—enters superior segment of right upper lobe. Preferentially on right side.
- While lying on right side-usually enters right upper lobe
- Frequency of location for obstruction is as follows: right main bronchus > left main bronchus > trachea > right lower bronchus > left lower bronchus > bilateral.
Pathways through the Diaphragm
- T8 Level (Caval opening)
- Inferior Vena Cava
- T10 Level (Esophageal Opening)
- Vagus Nerve
- Esophageal Branches Left Gastric Vessels
- T12 Level (Aortic opening)
- Thoracic Duct
- Azygos Vein
Physiologic Dead Space (VD)
- Tidal Volume (VT)
- Partial pressure of arterial CO2 (PaCO2)
- Partial pressure of CO2 in expired air (PECO2)
- VD = TV x (PaCO2-PECO2) / PaCO2
- VA = VE − VD
- Total volume of gas entering lungs per minute
- VE = VT × RR
- Volume of gas per unit time that reaches alveoli
- VA = (VT − VD) × RR
- Respiratory rate (RR) = 12–20 breaths/min
- VT = 500 mL/breath
- VD = 150 mL/breath
Lung and chest wall
- Tendency for lungs to collapse inward and chest wall to spring outward.
- At FRC (Functional Residual Capacity), inward pull of lung is balanced by outward pull of chest wall, and system pressure is atmospheric.
- Elastic properties of both chest wall and lungs determine their combined volume.
- At FRC, airway and alveolar pressures are 0, and intra pleural pressure is negative (prevents atelectasis). PVR is at minimum.
- Change in lung volume for a change in pressure; expressed as ΔV/ΔP and is inversely proportional to wall stiffness.
- High compliance = lung easier to fill (emphysema, normal aging),
- Lower compliance = lung harder to fill (pulmonary fibrosis, pneumonia, NRDS, pulmonary edema)
- Surfactant increases compliance.
- Lung inflation curve follows a different curve than the lung deflation curve due to need to overcome surface tension forces in inflation.
- Embryonic globins: ζ and ε.
- Fetal hemoglobin (HbF) = α2γ2
- Adult hemoglobin (HbA1) = α2β2
- HbF has higher affinity for O2 due to less avid binding of 2,3-BPG, allowing HbF to extract O2 from maternal hemoglobin (HbA1 and HbA2) across the placenta.
- HbA2 (α2δ2) is a form of adult hemoglobin present in small amounts.
- Hemoglobin Has Four Iron Hemes
- Lots Of Hemoglobin In Red Blood Cells
- High O2 Levels Increase O2 Binding
- High Temperature Reduces O2 Binding
- High CO2 Levels Reduce O2 Binding
- Low pH Reduces O2 Binding
- Myoglobin Binds Oxygen in Muscle
Hemoglobin modifications (Methemoglobinemia and CO poisoning)
- Lead to tissue hypoxia from decreased O2 saturation and decreased O2 content.
- Oxidized form of Hb (ferric, Fe3+) that does not bind O2 as readily, but has increased affinity for cyanide.
- PaO2 normal; SaO2 decreased
- Iron in Hb is normally in a reduced state (ferrous, Fe2+). Fe2+ binds O2.
- Methemoglobinemia may present with cyanosis and chocolate-colored blood.
- Induced methemoglobinemia (using nitrites, followed by thiosulfate) may be used to treat cyanide poisoning.
- Nitrites (eg, from dietary intake or polluted/high altitude water sources) and benzocaine cause poisoning by oxidizing Fe2+ to Fe3+.
- Methemoglobinemia can also be an inherited disorder. Autosomal recessive. Deficient enzme: Cytochrome b5 reductase (Normally turns methemoglobin to hemoglobin)
- Methemoglobinemia can be treated with methylene blue and vitamin C.
- Form of Hb bound to CO in place of O2.
- Causes decreased oxygen-binding capacity with left shift in oxygen-hemoglobin dissociation curve.
- Pao2 normal; SaO2 decreased
- Decreases O2 unloading in tissues.
- CO binds competitively to Hb and with 200× greater affinity than O2.
- CO poisoning can present with headaches, dizziness, and cherry red skin.
- May be caused by fires, car exhaust, or gas heaters.
- Early sign of exposure is headache; significant exposure leads to coma and death.
- Treat with 100% O2 and hyperbaric O2.
- Normally a low-resistance, high-compliance system.
- PO2 and PCO2 exert opposite effects on pulmonary and systemic circulation.
- A decrease in PAO2 causes a hypoxic vasoconstriction that shifts blood away from poorly ventilated regions of lung to well-ventilated regions of lung.
- O2 (normal health), CO2, N2O.
- Gas equilibrates early along the length of the capillary.
- Diffusion can be increased only if blood flow increases.
- O2 (emphysema, fibrosis), CO.
- Gas does not equilibrate by the time blood reaches the end of the capillary.
Pulmonary Diffusion Equation
- Diffusion: V gas = A × Dk × (P1 – P2 / T )
- A decreases in emphysema
- T increases in pulmonary fibrosis.
- DLCO is the extent to which CO, a surrogate for O2, passes from air sacs of lungs into blood.
Pulmonary vascular resistance
- PVR = (P pulm artery – P L atrium) / cardiac output
- Remember: ΔP = Q × R, so R = ΔP / Q
- R = 8ηl / πr4
Alveolar Gas Equation
- Partial Pressure of Alveolar Oxygen (PAO2)
- Partial Pressure of Oxygen in the Inspired Air (PIO2)
- PIO2 Normally Approximated = 150 mmHg
- Arterial Partial Pressure of CO2 (PaCO2)
- Respiratory Quotient (R)
- R Normally Approximated = 0.8
- PAO2 = PIO2 - (PaCO2/R)
- Partial pressure of alveolar oxygen (PAO2)
- Partial Pressure of Arterial O2 (PaO2)
- Normal 10 to 15 mmHg
- Hypoxemia with an Abnormal A-a Gradient
- Diffusion problem
- Shunting (Low V/Q)
- Dead space (high V/Q)
- Decreased O2 delivery to tissue
- Decreased cardiac output
- CO poisoning
- Decreased PaO2
- Normal A-a gradient
- High altitude
- Hypoventilation (eg, opioid use)
- Increased A-a gradient
- V/Q mismatch
- Diffusion limitation (eg, fibrosis)
- Right-to-left shunt
- Loss of blood flow
- Impeded arterial flow
- Decreased venous drainage