Caisson's Disease (Decompression Sickness / "The Bends")

Definition

• Robbins Pathologic Basis of Disease

Etiology / At-Risk Groups

• Scuba and deep-sea divers (most common)
• Underwater construction workers
• Aviators in unpressurized aircraft
• Astronauts (rapid decompression)
• Caisson workers (pressurized tunnel/bridge construction)

Pathophysiology (Henry's and Boyle's Laws)

1. Henry's Law: At high ambient pressure, increased amounts of nitrogen dissolve in blood and tissues (especially fat, where N₂ is 5x more soluble than water).
2. Rapid decompression (ascent): Ambient pressure drops quickly; tissues become supersaturated with nitrogen.
3. Bubble formation: Nitrogen comes out of solution as gas bubbles in blood vessels and tissues.
4. Consequences of bubbles:
   • Mechanical compression of surrounding tissues
   • Vascular occlusion → endothelial damage, ischemia, inflammation
   • Activation of inflammatory mediators and reperfusion injury
   • In the spinal cord: bubbles trapped in spinal vessels → ischemic myelopathy (predominantly upper thoracic cord, white matter, posterior > lateral > anterior columns)

• Goldman-Cecil Medicine; Adams and Victor's Principles of Neurology

Classification

Clinical Features

Type I - "The Bends"

• Joint pain (mild to severe) - classically knees, hips, shoulders
• Numbness/tingling in extremities
• Skin rashes, pruritus
• Lymphedema

Type II - Systemic/Neurological

• Neurological: Spastic myelopathy (upper thoracic cord), ataxia, aphasia, visual disturbances, paralysis, incontinence, confusion, loss of consciousness
• Cardiopulmonary ("Chokes"): Cough, substernal chest pain, tachypnea, dyspnea, pulmonary edema, respiratory distress; caused by gas bubbles in pulmonary vasculature causing edema, hemorrhage, and focal atelectasis/emphysema
• Otic: Vertigo, tinnitus, hearing loss (may be permanent if inner ear involved)
• Systemic: Fatigue, hypovolemic shock

Chronic Form - Caisson Disease (stricto sensu)

• Persistence of gas emboli in the skeletal system → avascular necrosis
• Common sites: femoral heads, tibia, humeri
• Robbins Pathologic Basis of Disease; Goldman-Cecil Medicine; Adams and Victor's Neurology

Spinal Cord Involvement (Myelopathy)

• Upper thoracic cord predominantly affected
• White matter more than gray matter; posterior columns > lateral > anterior columns
• May present as complete transverse myelopathy initially, then partially recover
• Can leave permanent asymmetric, incomplete deficit
• Residual: spasticity (lateral column damage) or leg numbness (posterior column damage)
• Adams and Victor's Principles of Neurology

Diagnosis

• Clinical - based on history of pressure exposure + compatible symptoms
• Symptoms can appear within minutes to 24 hours after ascent (dives ≥20 feet)
• MRI: spinal cord ischemic lesions (upper thoracic)
• Arterial gas embolism: may show CNS or cardiac effects

Treatment

• Contact Divers Alert Network (DAN): 919-684-9111 (24-hour consultation)
• Tintinalli's Emergency Medicine; Murray & Nadel's Respiratory Medicine; Adams and Victor's Neurology

Pathological Findings (Autopsy / Chronic)

• Spinal cord: ischemic necrosis over 1-2 segments; occlusion of small arteries and veins
• Skeletal system: multiple foci of ischemic (avascular) necrosis at femoral heads, tibia, humeri (from persistent gas emboli)
• Lungs: edema, hemorrhage, focal atelectasis/emphysema
• Fat embolism may coexist (N₂ dissolves preferentially in fat; fat may be released)
• Robbins Pathologic Basis of Disease

Forensic Significance

• Deaths may occur from pulmonary barotrauma, air embolism, or severe neurological injury
• Annual incidence: ~1 case per 5,000-10,000 recreational dives; up to 10% of cases requiring recompression are fatal
• Must be distinguished from high-altitude decompression sickness (similar symptoms, different circumstances)
• Pulmonary barotrauma is the second leading cause of death among divers
• Goldman-Cecil Medicine; P.C. Dikshit Forensic Medicine

Summary Box (SAQ Quick Recall)

Cause: Rapid ascent from high pressure → N₂ supersaturation → gas bubbles
Acute: Joint pain (bends), chokes (pulmonary), neurological myelopathy
Chronic: Avascular necrosis (femoral head, tibia, humerus)
Spinal cord: Upper thoracic, white > gray, posterior > anterior columns
Treatment: Hyperbaric oxygen (recompression) - U.S. Navy Table 6
Prevention: Slow, staged ascent; decompression stops

Definitions: Abnormal Breathing Patterns

1. Apnoea (Apnea)

• In clinical practice (e.g., sleep studies), an apnoea is defined as a >90% reduction in nasal airflow lasting for at least 10 seconds, regardless of whether it causes oxygen desaturation.
• May be central (no respiratory effort), obstructive (effort present but airway blocked), or mixed.
• Physiological apnoea occurs briefly after a deep breath (Hering-Breuer reflex) or voluntarily.
• Pathological apnoea occurs in obstructive sleep apnoea (OSA), neonatal apnoea, drug-induced respiratory depression, and brainstem injury.

"An apnoea is regarded as a completed cessation of airflow (more than 90% reduction in nasal airflow/pressure signal amplitude) for at least 10 seconds."

• Scott-Brown's Otorhinolaryngology Head & Neck Surgery

2. Hyperpnoea (Hyperpnea)

• The patient may or may not be conscious of the increased ventilation.
• It is an objective sign, not a symptom.
• Causes include: exercise (physiological), fever, metabolic acidosis (e.g., diabetic ketoacidosis - Kussmaul breathing), anaemia, hypoxia, high altitude.
• Distinguished from dyspnoea: hyperpnoea does not require the patient to feel uncomfortable - it is simply increased ventilation.

"Hyperpnea is the general term for an increase in the rate or depth of breathing regardless of the patient's subjective sensations."

• Ganong's Review of Medical Physiology, 26th Edition

3. Tachypnoea (Tachypnea)

• It is an objective sign observed by the clinician.
• The rate is increased but tidal volume may be relatively shallow (unlike hyperpnoea, where depth also increases).
• Clinically significant thresholds: mild tachypnoea = 20-30 breaths/min; severe = >30-35 breaths/min (indicates impending respiratory failure).
• Tachypnoea is indicative of increased drive to breathe, but does not necessarily indicate alveolar hyperventilation (which is determined by rate AND tidal volume together).
• Causes: pneumonia, pulmonary embolism, heart failure, sepsis, pain, anxiety, fever, metabolic acidosis.

"Tachypnea is rapid, shallow breathing." "Tachypnea is indicative of an increased drive to breathe, although it is not necessarily evidence of alveolar hyperventilation, which is determined by rate and tidal volume."

• Ganong's Review of Medical Physiology; Murray & Nadel's Textbook of Respiratory Medicine

4. Dyspnoea (Dyspnea)

"Dyspnea is a term used to characterize a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity. The experience derives from interactions among multiple physiological, psychological, social, and environmental factors, and it may induce secondary physiological and behavioral responses."

• It is a symptom (reported by the patient), not a sign (observed by the clinician).
• It is distinct from respiratory distress (which is the physical manifestation observed by others).
• Multiple neural pathways are involved; causes include hypercapnia, hypoxia, and increased work of breathing.
• Qualitative descriptors: "air hunger / not getting enough air" (increased respiratory drive); "chest tightness" (bronchoconstriction); "increased effort/work of breathing" (mechanical load or muscle weakness); "inability to get a deep breath" (dynamic hyperinflation).
• Murray & Nadel's Textbook of Respiratory Medicine; Ganong's Review of Medical Physiology; Goldman-Cecil Medicine

Comparison Table

Key Distinctions to Remember

• Dyspnoea vs Hyperpnoea: Hyperpnoea is an objective increase in ventilation; dyspnoea is the subjective feeling of breathing difficulty. They often coexist but are not the same - a patient can have hyperpnoea without dyspnoea (e.g., during mild exercise).
• Tachypnoea vs Hyperpnoea: Tachypnoea = fast + shallow; Hyperpnoea = increased rate and/or depth.
• Apnoea vs Hypopnoea: Apnoea = >90% cessation of airflow; Hypopnoea = partial reduction in airflow (usually >30-50% reduction).
• A normal individual does not become conscious of breathing until ventilation is doubled, and breathing is not uncomfortable until ventilation is tripled or quadrupled (Ganong's).

Surfactant - Complete SAQ Answer

A) Composition

Lipid Component (~90% of total mass)

Protein Component (~10% of total mass)

• The superficial layer (facing alveolar air) is made of surface-active phospholipids, notably DPPC.
• The deeper layer (hypophase) consists of surface-active phospholipids linked to protein.

"The superficial layer of the film facing the alveolar air is made up of surface-active phospholipids, notably dipalmitoyl lecithin. The deeper layer, termed the hypophase, consists of surface-active phospholipids linked to protein."

• Fishman's Pulmonary Diseases and Disorders; Histology: A Text and Atlas (Ross & Pawlina)

B) Source and Secretion

Source

• Surfactant is produced exclusively by Type II alveolar pneumocytes (Type II alveolar epithelial cells), also known as granular pneumocytes or septal cells.
• Type II cells make up only ~5% of the alveolar surface area but are metabolically the most active alveolar cells.
• SP-B is also expressed by club cells (Clara cells) of the bronchioles, but SP-C is exclusive to Type II cells.

Intracellular Synthesis and Storage

1. Phospholipids and proteins are synthesized in the endoplasmic reticulum.
2. Processed via the Golgi complex and multivesicular bodies.
3. Stored intracellularly in characteristic membrane-bound organelles called lamellar bodies (intracellular storage form of surfactant).
   • Lamellar bodies appear as concentric whorls of lipid membranes on electron microscopy.

Secretion

• Secreted by constitutive exocytosis - the lamellar body fuses with the apical plasma membrane and releases surfactant into the alveolar lining fluid.
• After secretion, surfactant undergoes structural change in the aqueous layer, forming a meshwork called tubular myelin, which is rich in surfactant apoproteins.
• From tubular myelin, it forms the surface film at the air-water interface.

Stimuli that INCREASE secretion:

• Hyperinflation of the lungs (sighing, yawning, deep breathing)
• Exercise
• Beta-adrenergic agonists (clinical use!)
• Corticosteroids - stimulate surfactant lipid and protein formation
• Labor itself stimulates surfactant synthesis
• Fetal stress / intrauterine growth restriction (raises cortisol)

Factors that SUPPRESS secretion / maturation:

• Prematurity (<35 weeks gestation) - Type II cells are immature
• Maternal diabetes (high fetal insulin suppresses surfactant synthesis)
• Elective cesarean section before labor onset

Removal

1. Alveolar macrophages degrade some surfactant.
2. Type II cells re-uptake the rest via endocytosis, then recycle or destroy it.

Fetal Development

• Surfactant synthesis begins after approximately week 20 of fetal gestation (in Type II cells as they differentiate).
• Clinically adequate quantities are produced after ~35 weeks gestation.
• A surge in maternal glucocorticoid levels just before birth triggers surfactant synthesis and secretion.

"The secretion of pulmonary surfactant occurs by constitutive exocytosis. In the fetus, both synthesis and secretion are quite low until immediately before birth, when a surge in maternal glucocorticoid levels triggers these processes."

• Medical Physiology (Boron & Boulpaep); Fishman's Pulmonary Diseases and Disorders

C) Functions

1. Reduces Alveolar Surface Tension (MOST IMPORTANT)

• By Laplace's law: Pressure = 2T/r - without surfactant, smaller alveoli (smaller radius) would have higher recoil pressure and empty into larger ones, causing atelectasis.
• Surfactant lowers surface tension in proportion to its concentration - as alveoli become smaller on expiration, surfactant becomes more concentrated on the surface and surface tension drops further, preventing collapse.
• This ensures equal pressure across alveoli of different sizes, maintaining alveolar stability.

2. Increases Lung Compliance

• By reducing surface tension, surfactant dramatically increases lung compliance (ease of inflation).
• Without surfactant, total elastic recoil increases by 2x or more, forcing the infant to exert tremendous effort with every breath.

3. Prevents Pulmonary Oedema

• Without surfactant, high surface tension would draw fluid from the interstitium into the alveolar space by a "sucking" effect, thickening the fluid layer and impairing gas diffusion.
• Surfactant keeps surface tension low, balancing the negative interstitial hydrostatic pressure and keeping alveoli dry.

4. Promotes Uniform Ventilation

• Surfactant allows alveoli to dynamically adjust their inflation/deflation rates, so that ventilation is uniform across alveoli of different sizes - preventing "fast alveoli" from emptying into "slow alveoli."

5. Reduces Work of Breathing

• By increasing compliance and stabilising alveoli, surfactant significantly reduces the muscular effort required for breathing.

6. Innate Immune Defence (SP-A and SP-D)

• SP-A and SP-D (collectins) bind to bacteria, viruses, and fungi, promoting opsonisation and phagocytosis by alveolar macrophages.
• SP-D participates in local inflammatory responses to acute lung injury and modulates immune responses to inhaled antigens.

"The pulmonary surfactant present at the alveolar air-water interface has three major effects: it increases compliance, it minimizes fluid accumulation, and it promotes uniform ventilation."

• Medical Physiology (Boron & Boulpaep); Fishman's Pulmonary Diseases and Disorders

D) Respiratory Distress Syndrome (RDS)

Also Known As:

• Infant / Neonatal Respiratory Distress Syndrome (IRDS / NRDS)
• Hyaline Membrane Disease (HMD)

Etiology

• < 28 weeks gestation: ~60% of infants affected
• 28-34 weeks: ~30%

• 34 weeks: < 5%

• Male gender
• Maternal diabetes (high fetal insulin suppresses surfactant)
• Cesarean section (before onset of labor)
• Perinatal asphyxia

Pathogenesis (Vicious Cycle)

1. Prematurity → Immature Type II pneumocytes → Reduced surfactant synthesis, storage, and release
2. Decreased alveolar surfactant → Increased alveolar surface tension → alveolar collapse (atelectasis)
3. Atelectasis → Impaired perfusion, hypoventilation
4. → Hypoxemia + CO₂ retention (acidosis)
5. Acidosis + hypoxia → Pulmonary vasoconstriction → Pulmonary hypoperfusion
6. Hypoperfusion → Endothelial damage and epithelial damage
7. Damage → Plasma leaks into alveoli → plasma proteins (fibrin, fibrinogen) mix with necrotic cells
8. → Formation of Hyaline Membranes → barrier to gas exchange
9. Hyaline membranes + surfactant inactivation → further surfactant deficiency (vicious cycle)

Morphology (Pathology)

• Lungs: Normal size but heavy, relatively airless, mottled purple color.
• Microscopy:
  • Poorly developed, collapsed (atelectatic) alveoli
  • Eosinophilic hyaline membranes lining respiratory bronchioles, alveolar ducts, and alveoli
  • Membranes contain: necrotic Type II pneumocytes + extravasated plasma proteins (mainly fibrin)
  • No significant neutrophilic infiltrate
  • If infant survives days: Type II pneumocyte proliferation + interstitial fibrosis (repair)

Clinical Features

• Presents within hours of birth
• Progressive tachypnoea, grunting, nasal flaring, intercostal retractions
• Cyanosis
• Worsens over first 2-3 days; recovery begins by day 3-4 (if treated)
• Chest X-ray: Diffuse ground-glass opacification ("white-out"), air bronchograms, diminished lung volumes

Treatment and Prevention

• Retinopathy of prematurity (retrolental fibroplasia) - VEGF dysregulation causing retinal neovascularization
• Bronchopulmonary dysplasia - decreased alveolar septation, dysmorphic capillary configuration

Adult RDS (ARDS) - Brief Note

• In adults, surfactant dysfunction occurs due to inactivation (not developmental deficiency).
• Causes: sepsis, trauma, aspiration, pneumonia, burns.
• Mechanism: microvascular injury → protein and fluid leak into alveoli → surfactant inactivated by albumin, immunoglobulins, fibrinogen, fatty acids, lyso-PC.
• Treatment: ventilatory support + prone positioning (exogenous surfactant has NOT been shown to benefit adult ARDS).
• Robbins & Kumar Basic Pathology; Fishman's Pulmonary Diseases and Disorders; Medical Physiology (Boron & Boulpaep); Histology: A Text and Atlas (Ross & Pawlina); Langman's Medical Embryology

Surfactant - Complete SAQ Answer

A) Composition

Lipid Component (~90%)

Protein Component (~10%) - Four Surfactant Apoproteins (SP)

• Superficial layer (facing alveolar air): surface-active phospholipids (mainly DPPC)
• Deep layer / Hypophase: surface-active phospholipids linked to protein

B) Source and Secretion

Source

• Type II alveolar pneumocytes (granular pneumocytes / septal cells) - the sole producers of surfactant.
• Type II cells cover only ~5% of alveolar surface but are metabolically the most active alveolar cells.
• SP-B is also expressed by club cells (Clara cells) of bronchioles; SP-C is exclusive to Type II cells.

Intracellular Synthesis Pathway

1. Phospholipids + proteins synthesized in endoplasmic reticulum
2. Processed via Golgi complex and multivesicular bodies
3. Stored in lamellar bodies (characteristic concentric whorled membrane organelles - intracellular storage form)

Secretion Steps

1. Lamellar body fuses with apical plasma membrane → exocytosis into alveolar lining fluid
2. Released surfactant forms a meshwork called tubular myelin (rich in SP apoproteins) in the aqueous layer
3. From tubular myelin → forms surface film at the air-water interface
4. Recycled back into Type II cells by endocytosis, or degraded by alveolar macrophages

Stimuli Increasing Secretion

• Lung hyperinflation (sighing, yawning, deep breathing)
• Exercise
• Beta-adrenergic agonists (clinical importance)
• Corticosteroids (stimulate synthesis of lipids AND proteins)
• Labor (stimulates synthesis)
• Fetal stress / intrauterine growth restriction (via increased cortisol)

Factors Suppressing Maturation

• Prematurity (<35 weeks) - immature Type II cells
• Maternal diabetes - high fetal insulin suppresses surfactant synthesis
• Elective caesarean section before labor onset

Fetal Development Timeline

• Type II cells differentiate and begin surfactant synthesis from ~week 20 of gestation
• Clinically adequate amounts produced after ~35 weeks gestation
• A surge in maternal glucocorticoids just before birth triggers the final maturation

C) Functions

1. Reduces Alveolar Surface Tension (Primary Function)

• By Laplace's Law: Pressure = 2T/r
• Without surfactant: small alveoli (small r) have higher recoil pressure and empty into larger ones → atelectasis
• Surfactant lowers tension as alveoli shrink (concentration rises at smaller surface area) → tension drops proportionally → prevents collapse on expiration

2. Increases Lung Compliance

• Lower surface tension = less elastic recoil = easier to inflate lungs
• Without surfactant, compliance drops 2x or more, forcing enormous inspiratory effort with every breath

3. Prevents Pulmonary Oedema

• High surface tension (without surfactant) would suck fluid from interstitium into alveoli
• Surfactant keeps tension low → alveoli remain dry → diffusion distance is minimized

4. Maintains Alveolar Stability (Equalises Pressure Across Alveoli)

• Small and large communicating alveoli maintain equal transpulmonary pressure
• Prevents small alveoli from emptying into large ones (prevents inter-alveolar instability)

5. Reduces Work of Breathing

• Improved compliance + alveolar stability = significantly less muscular effort required per breath

6. Promotes Uniform Ventilation

• Dynamically adjusts surface tension during inflation/deflation cycles → uniform ventilation across all alveoli

7. Innate Immune Defence (SP-A and SP-D)

• Opsonise bacteria, viruses, fungi → promote phagocytosis by alveolar macrophages
• Modulate local inflammatory response to inhaled antigens and acute lung injury

D) Respiratory Distress Syndrome (RDS)

Aetiology

• < 28 weeks: ~60%
• 28-34 weeks: ~30%

• 34 weeks: < 5%

Pathogenesis - The Vicious Cycle

Morphology (Histopathology)

• Macroscopy: Lungs normal size but heavy, airless, mottled purple
• Microscopy:
  • Collapsed (atelectatic) alveoli alternating with dilated alveolar ducts
  • Eosinophilic hyaline membranes lining respiratory bronchioles, alveolar ducts, and alveoli
  • Membranes composed of: necrotic Type II pneumocytes + extravasated plasma proteins (fibrin)
  • No significant neutrophilic infiltrate
  • Survivors: Type II pneumocyte proliferation + interstitial fibrosis (repair phase)

Clinical Features

• Presents within hours of birth
• Progressive tachypnoea, grunting (positive end-expiratory pressure self-generated), nasal flaring, intercostal retractions
• Cyanosis
• Worsens over 2-3 days; recovery begins by day 3-4 if treated
• CXR: Diffuse bilateral ground-glass ("white-out"), air bronchograms, low lung volumes (atelectasis)

Treatment and Prevention

• Retinopathy of prematurity (retrolental fibroplasia) - VEGF dysregulation → retinal neovascularisation
• Bronchopulmonary dysplasia - decreased alveolar septation, dysmorphic capillary configuration

ARDS in Adults - Key Difference

• Robbins & Kumar Basic Pathology; Fishman's Pulmonary Diseases and Disorders; Medical Physiology (Boron & Boulpaep); Histology: A Text and Atlas (Ross & Pawlina); Langman's Medical Embryology