Pathophysiology Exam 3
Pulmonary System Anatomy & Blood Supply
Upper (Conducting) Portion
Nasopharynx, Oropharynx, Laryngopharynx
Lower (Respiratory) Portion
Larynx, Trachea, Bronchi, Bronchopulmonary segments, Alveoli
Dual blood supply
Bronchial artery system (nutritive)
Pulmonary circulation (gas-exchange)
Alveolar Cell Types & Surfactant
Type I cells
Thin epithelial structural cells → primary site of gas exchange
Type II cells
Produce surfactant (phospholipid); REDUCES surface tension, keeps alveoli open, eases inspiration
Surfactant deficiency = ↑ work of breathing & alveolar collapse
Autonomic Control of Airways
Parasympathetic (vagus, acetylcholine)
Bronchial smooth-muscle constriction
Sympathetic (β₂-adrenergic, epinephrine)
Smooth-muscle relaxation → bronchodilation
Mechanics of Breathing
Inhalation (active)
Diaphragm contracts & descends, external intercostals elevate ribs → ↑ thoracic volume, create negative intrapleural pressure; lungs expand against natural elastic recoil
Exhalation (passive at rest)
Diaphragm relaxes, ribs fall → ↓ volume; can become active (internal intercostals, abdominals) during forceful breathing
End-expiration retains Functional Residual Capacity; surfactant keeps alveoli patent
Factors Affecting Ventilation
Airway resistance
R \propto \frac{1}{\text{radius}^4}; ↑ with mucus, bronchospasm, stress, deconditioning, age
Highest at nose (turbulence); lowest in small bronchioles (laminar flow)
Neonates > adults
Lung compliance C = \frac{\Delta V}{\Delta P}
↑ in neonates/children (flexible chest wall)
↓ in elderly (rigid wall, loss of elastin)
Distribution (upright)
Ventilation greatest at lung bases, less at apices; difference diminishes supine
Neurologic control
Respiratory centers: pons & medulla; phrenic nerves drive diaphragm; dorsal medullary neurons → inspiration
Diffusion & Gas Transport
Gas moves high → low partial pressure (Fick’s Law)
Six diffusion barriers: surfactant, alveolar epithelium, interstitium, capillary endothelium, plasma, RBC membrane
Altered Alveolar Ventilation
Hypoventilation → ↑ PaCO_2 (respiratory acidosis)
Causes: morphine, barbiturates, obesity, MG, OSA, thoraco-abdominal surgery, muscle paralysis
Hyperventilation → ↓ PaCO_2 (respiratory alkalosis)
Causes: pain, fever, anxiety, COPD flare, sepsis, high altitude, brainstem injury
Hypoxemia/hypoxia = deficient O₂ delivery
Obstructive vs. Restrictive Patterns
Obstructive (problem getting air OUT)
↑ resistance, wheeze, hyper-inflated CXR
Restrictive (problem getting air IN)
↓ compliance/volume, dyspnea, cyanosis, stiff lungs/chest wall
Obstructive Disorders
Asthma
Reversible airway obstruction, hyper-reactivity, inflammation
Symptoms: cough, wheeze, chest tightness, dyspnea, thick sputum
Epidemiology: 5–12 % U.S.; children; ↑ risk African-Americans, inner-city, preterm
Intrinsic (non-allergic, adult, not IgE) vs Extrinsic (allergic, pediatric, IgE-mediated)
Immediate phase: antigen–IgE on mast cell → release histamine, leukotrienes, PGs, bradykinin, etc.
Late phase: recruited eosinophils/neutrophils → epithelial injury, mucus, smooth muscle hypertrophy
Histology: inflammation, lumen narrowing, ↑ mucus, smooth-muscle hyperplasia, ↑ eosinophils
Diagnostics: peak flow, FEV₁; sputum w/ Charcot–Leyden crystals, Curschmann spirals
Therapy: trigger avoidance, inhaled β₂-agonists, steroids, leukotriene modifiers, O₂, immunotherapy
Chronic Bronchitis (Type B COPD “Blue Bloater”)
Productive cough ≥3 mo/yr for ≥2 yrs; persistent, irreversible
Etiology: smoking (90 %), recurrent infections, irritants
Pathogenesis: mucosal inflammation → mucus gland/goblet hyperplasia, bronchial wall thickening, mucus plugs; pulmonary HTN → cor pulmonale
Clinical: DOE, copious sputum, morning cough, edema, cyanosis
CXR: ↑ vascular markings, congested fields
Management: smoking cessation, bronchodilators, hydration, pulmonary rehab
Emphysema (Type A COPD “Pink Puffer”)
Irreversible enlargement of airspaces w/ alveolar wall destruction; loss of elastic recoil; airway collapse on expiration → air-trapping
Etiology: smoking >70 pack-yrs, α₁-antitrypsin deficiency, pollutants
Pathogenesis: neutrophil elastase/protease injury; loss of radial traction ↓ airway patency
Clinical: thin, barrel chest, pursed-lip breathing, minimal cough, blebs/bullae → risk pneumothorax
PFT: ↓ FEV₁, ↓ FVC, ↑ TLC; CXR hyperinflation
Treatment: smoking cessation, O₂, inhaled anticholinergics/β₂, steroids, antibiotics for infection
Bronchiectasis
Irreversible bronchial dilation due to chronic infection/inflammation; often secondary to CF, necrotizing pneumonias
Pathology: loss of cilia, squamous metaplasia, pus, necrosis
Cystic Fibrosis
Autosomal-recessive CFTR mutation → faulty Cl⁻ transport; thick secretions in lungs, pancreas, GI; recurrent infections; airflow & suppurative pattern
Restrictive Lung Diseases
Categories
Parenchymal (fibrotic ILD), Atelectatic disorders (ARDS/IRDS)
Pleural, chest wall, neuromuscular, obesity
Diffuse Interstitial Lung Disease (Pulmonary Fibrosis)
Immune injury → inflammation → fibroblast proliferation → collagen deposition → thickened alveolar walls → irreversible fibrosis
Manifestations: progressive DOE & desaturation, dry cough, bibasilar crackles, clubbing, weight loss
Dx: CXR, HRCT, lung biopsy, BAL
Tx: smoking cessation, avoid triggers, steroids, immunosuppressants, lung transplant
Sarcoidosis
Multi-system granulomatous disease; non-caseating epithelioid granulomas ± asteroid bodies
Etiology unknown; exaggerated T-cell response; affects lungs, lymph nodes, skin, eyes
Clinical: fatigue, fever, weight loss, dyspnea, dry cough, erythema nodosum, hepatosplenomegaly
Dx: BAL (↑ CD4/CD8), transbronchial biopsy (granulomas), CXR staging
Tx: corticosteroids, immunosuppressants
Acute Respiratory Distress Syndrome (ARDS)
Alveolar–capillary damage secondary to trauma, sepsis (>40 %), aspiration, shock
Pathology: inflammatory cytokines → leaky capillaries (non-cardiogenic edema), surfactant loss, atelectasis, fibrosis
Findings: severe refractory hypoxemia, ↓ compliance, diffuse “whiteout”, fluffy infiltrates
Early: dyspnea, rapid shallow breathing; Late: tachypnea, crackles, cyanosis
ABG: hypoxia, acidosis, hypercapnia
Tx: treat cause, supportive ventilation (low VT, PEEP), fluid management, O₂
Neuromuscular & Chest Wall Causes of Restriction
Neuromuscular: Poliomyelitis, ALS, Duchenne Muscular Dystrophy, Guillain-Barré (ascending paralysis), Myasthenia Gravis (NM-junction defect)
All may lead to respiratory muscle weakness → hypoventilation
Chest wall deformities: Kyphoscoliosis, Ankylosing spondylitis, Flail chest, Morbid obesity
Infectious/Inflammatory Lung Diseases
Pneumonia
Infection of alveoli/interstitium by bacteria, virus, fungi
Routes: aspiration (25–35 %), inhalation, hematogenous
Community vs Hospital acquired; viral often “interstitial” pattern
Pathogenesis: organisms colonize → inflammation → alveolar exudate (except viral)
Manifestations: fever, chills, purulent cough, crackles/rales, bronchial breath sounds
Dx: CXR infiltrate, sputum C&S, WBC >15{,}000 (bacterial)
Tx: organism-directed antibiotics
Fluid & Electrolyte Physiology
Forces: hydrostatic (push out) vs osmotic (pull in); govern capillary–interstitial exchange
Fluid homeostasis: intake, absorption, distribution, excretion (kidney, GI, skin, lungs)
Regulators
Hypothalamic thirst & ADH (water retention)
Renin–Angiotensin–Aldosterone System: renin → Ang II → aldosterone → Na⁺ & water reabsorption
Natriuretic peptides (ANP, BNP, CNP): oppose RAAS, promote natriuresis/diuresis
Disorders
Dehydration (water ± Na⁺ deficit)
Edema (↑ hydrostatic, ↓ oncotic, lymph block, Na⁺/water retention)
Key Electrolytes & Imbalances
Sodium 135–145\,\text{mEq·L}^{-1}
Hyponatremia <135: cramps, weakness, hypotension, confusion
Hypernatremia >145: thirst, dry mucosa, restlessness
Potassium 3.5–5\,\text{mEq·L}^{-1}
Hypokalemia <3.5: weakness, arrhythmia, polyuria
Hyperkalemia >5: flaccid paralysis, abdominal cramps, cardiac arrest
Chloride 98–108\,\text{mEq·L}^{-1}
Hypo: tetany, shallow breaths; Hyper: metabolic acidosis, deep breathing
Calcium 8.5–10.5\,\text{mg·dL}^{-1}
Hypo: tetany, seizures, arrhythmia
Hyper: fatigue, constipation, arrhythmia
Magnesium 1.5–2.5\,\text{mEq·L}^{-1}
Hypo: cramps, arrhythmia; Hyper: ↓ reflexes, respiratory depression
Phosphate 2.5–4.5\,\text{mg·dL}^{-1}
Hypo: weakness, bone pain; Hyper often asymptomatic
Acid–Base Fundamentals
pH scale: <7 acidic, >7 basic; arterial blood 7.35–7.45
Buffers: hemoglobin, bicarbonate, phosphate, proteins stabilize pH (Henderson–Hasselbalch)
Volatile acid: CO_2 (lungs handle rapid changes)
Fixed acids: lactic, ketoacids (kidneys excrete H^+, reabsorb HCO_3^-)
Primary Disorders & Compensation
Metabolic Acidosis: ↓ pH, ↓ HCO3^-, ↓ PCO2 (resp hyperventilation) e.g., DKA, diarrhea
Metabolic Alkalosis: ↑ pH, ↑ HCO3^-, ↑ PCO2 (hypoventilation) e.g., vomiting
Respiratory Acidosis: ↓ pH, ↑ PCO2, ↑ HCO3^- (renal retention) e.g., COPD
Respiratory Alkalosis: ↑ pH, ↓ PCO2, ↓ HCO3^- (renal excretion) e.g., high altitude, anxiety
Clinical Pearls & Connections
Elderly: ↓ compliance, ↑ rigidity → predispose to restrictive changes and hypoventilation
Neonates: ↑ compliance but ↑ airway resistance; surfactant crucial (IRDS if deficient)
Smoking is common denominator in chronic bronchitis/emphysema and a major ARDS risk via aspiration & infection
α₁-antitrypsin deficiency illustrates genetic susceptibility; parallels CF in inherited obstructive pathology
Natriuretic peptides clinically measured (BNP) to differentiate cardiogenic vs non-cardiogenic pulmonary edema (e.g., ARDS)
Acid–base disturbances often coexist with electrolyte shifts (e.g., acidosis drives hyperkalemia)