Pathophysiology
P-II-17. Respiratory disease, Case 4
呼吸器疾患 症例4
Case IV — Short case history of Mrs. S. O. (idiopathic pulmonary fibrosis)
Short case history:
- In 2004 surgical lung biopsy: “usual interstitial pneumonia (UIP)” = idiopathic pulmonary fibrosis
- 2004 – January 2010, Sopron: several systemic steroid + azathioprine therapies, but her state gradually deteriorated
- January 2010: Admission to the Pulmonology Clinic for examinations for lung transplantation
January 2010 — main complaints, physical signs and symptoms:
- Severe dyspnea on exertion (desaturation, cyanosis)
- No dyspnea at rest
- Cushing appearance
- Coarse crackles over the lungs
- 6-minute walking distance: 259 m (reference value > 600 m)
Imaging:
- Posteroanterior chest X-ray: prominent diffuse reticular silhouettes
- CT (January 2010): honeycombing and traction bronchiectasis
Pulmonary function (Summer 2010): flow rate–volume curve; DLCO: 62%, total capacity: 41%.
Blood gas, chemistry:
- pO2: 40 mmHg; with 8 l/min O2 pO2: 55 mmHg
- pCO2: 30 mmHg (VA = 6 l/min)
- CRP: ~40 mg/l
- Sedimentation: ~50 mm/h
- LDH: 720 U/l
- HbA1c: 9%
- Chol.: 6.9 mmol/l
- Trig.: 4.1 mmol/l
- Glu.: 9.1 mmol/l
- Lab results of kidneys, liver, bone marrow are within reference range
Invasive cardiology results:
- Pulm. art. pressure: 39/19 mmHg, mean pressure: 28 mmHg
- Coronary perfusion: dominance of the left ventricle (physiological)
January–July 2010:
- Recurring bronchopneumonia: Pseudomonas aeruginosa, could be treated
- Committee on Organ Transplantation: although all required objectives were met, she was considered ineligible (constitution)
Days before death and the circumstances of death:
- Low fever, high CRP, total load intolerance, circulation is compensated. With O2 therapy pO2 55 mmHg, pCO2 30 mmHg.
- At night during care (bedpan) suddenly occurring cyanosis, syncope, circulatory collapse and respiratory failure, unsuccessful resuscitation.
Autopsy results (I):
- Heart weight: 410 g (norm: 350 g)
- Right heart chambers are significantly dilated
- Wall thickness of the right ventricle: 3 mm
- Wall thickness of the left ventricle: 12 mm
- Valves are normal, the muscles are homogeneous, brownish
- Yellow plaques can be seen on the inner wall of the coronary arteries
Autopsy results (II):
- Smooth pleura
- Fine granular lung surface due to the unevenness of the parenchyma
- Lung parenchyma is firm, dense, air spaces are hardly visible
- Pus drainage from the cut surface of the basal lobes bilaterally
- Free lumen of the pulmonary arteries, yellow plaques on the inner walls
- Spleen parenchyma malacia was observed, plenty scraping
- Cortex of the adrenal glands became thin
- Urinary bladder nodular hyperemia of the mucous membrane
Lung histology: decreased air content, lymphocyte infiltration, connective tissue accumulation, hyperemia, bronchial lumen is filled with exudate, vessel walls are thick.
Summary — Mrs. S. O. (1957-2010):
- Immediate cause of death: dilatatio ventriculi dextri cordis
- Comorbidity discovered by autopsy: bilateral bronchopneumonia
- Primary disease: pulmonary fibrosis of unknown origin (idiopathic)
Key Quotes & What They Tell Us
| Quote / Value | Interpretation |
|---|---|
| Biopsy: “usual interstitial pneumonia (UIP)” = idiopathic pulmonary fibrosis | Histological UIP pattern → confirms idiopathic pulmonary fibrosis (IPF) |
| CT: “honeycombing and traction bronchiectasis”; X-ray reticular shadows | Classic imaging of advanced fibrotic lung disease |
| DLCO 62%, total capacity 41% | Restrictive pattern with impaired diffusion → typical of interstitial fibrosis |
| “Severe dyspnea on exertion (desaturation, cyanosis)”; 6-min walk 259 m; coarse crackles | Exercise-induced hypoxaemia and reduced capacity from stiff, poorly diffusing lungs |
| Pulmonary artery pressure 39/19, mean 28 mmHg; right heart chambers dilated | Secondary pulmonary hypertension → cor pulmonale (right heart strain/failure) |
| “Immediate cause of death: dilatatio ventriculi dextri cordis” | Death from right ventricular dilatation/failure driven by chronic pulmonary hypertension |
| Recurrent Pseudomonas bronchopneumonia; autopsy bilateral bronchopneumonia | Infective complications of end-stage fibrotic lung |
| Cushing appearance; HbA1c 9%, glucose 9.1 | Long-term steroid therapy → iatrogenic Cushingoid features and steroid-induced hyperglycaemia |
Key Points
- Diagnosis: Idiopathic pulmonary fibrosis (UIP pattern), progressive and ultimately fatal.
- Physiology: Restrictive defect (low TLC) with reduced DLCO and severe exertional hypoxaemia.
- Imaging hallmark: Honeycombing and traction bronchiectasis on CT.
- Fatal pathway: Chronic hypoxaemia/fibrosis → pulmonary hypertension → cor pulmonale → right ventricular dilatation and failure (cause of death).
- Complications: Recurrent Pseudomonas bronchopneumonia and steroid-related side effects (Cushingoid habitus, hyperglycaemia).
- Course: Refractory to steroids/azathioprine; transplantation was the only option but she was deemed ineligible.
一問一答
▶What is the diagnosis in a patient with biopsy-proven UIP, honeycombing on CT, and progressive exertional dyspnoea?
Idiopathic pulmonary fibrosis (IPF).
▶What histological pattern defines idiopathic pulmonary fibrosis?
Usual interstitial pneumonia (UIP).
▶What are the classic CT findings of advanced pulmonary fibrosis?
Honeycombing and traction bronchiectasis (with reticular shadowing).
▶What pulmonary function pattern is seen in IPF?
A restrictive pattern (low total lung capacity) with reduced diffusing capacity (DLCO).
▶Why is DLCO reduced in pulmonary fibrosis?
Thickened, fibrotic alveolar-capillary membranes impair gas diffusion.
▶Why does this patient desaturate on exertion but not at rest?
Increased oxygen demand and faster transit time during exercise unmask the diffusion limitation of the fibrotic lung.
▶What lung sound is characteristic of pulmonary fibrosis?
Fine/coarse end-inspiratory crackles (often 'Velcro' crackles).
▶How does pulmonary fibrosis lead to cor pulmonale?
Chronic hypoxaemia and vascular destruction cause pulmonary hypertension, which strains and ultimately fails the right ventricle.
▶What was the immediate cause of death in this patient?
Right ventricular dilatation/failure (dilatatio ventriculi dextri cordis).
▶What autopsy findings confirmed pulmonary hypertension / right heart strain?
A dilated, enlarged right heart (raised heart weight) with thin right-ventricular wall from dilatation.
▶What chronic infection repeatedly complicated this patient's fibrotic lung?
Recurrent Pseudomonas aeruginosa bronchopneumonia.
▶Why does this patient have a Cushingoid appearance and high HbA1c?
Long-term systemic corticosteroid therapy caused iatrogenic Cushing's features and steroid-induced hyperglycaemia.
▶What does a reduced 6-minute walk distance (259 m vs >600 m) indicate?
Severely impaired exercise capacity and exertional hypoxaemia from advanced lung disease.
▶What is the definitive treatment for end-stage idiopathic pulmonary fibrosis?
Lung transplantation.
▶How does restrictive lung disease differ from obstructive lung disease on spirometry?
Restrictive: reduced lung volumes (low TLC, FVC) with preserved/raised FEV1/FVC; obstructive: low FEV1/FVC with air trapping.
▶Why is the lung in pulmonary fibrosis described as 'stiff'?
Accumulated collagen/connective tissue reduces compliance, making the lungs hard to expand.
▶Why was this patient's disease refractory to steroids and azathioprine?
Idiopathic pulmonary fibrosis is driven by fibrosis rather than reversible inflammation, so immunosuppression is largely ineffective.
▶What histological features were seen in this fibrotic lung?
Decreased air content, lymphocyte infiltration, connective-tissue accumulation, hyperaemia, and exudate-filled bronchi with thickened vessel walls.
▶Why are patients with end-stage fibrotic lungs prone to recurrent pneumonia?
Distorted architecture, impaired clearance, and bronchiectasis promote bacterial colonization and infection.
▶Why does this patient's PaO2 remain low (55 mmHg) even on 8 L/min oxygen?
Severe diffusion impairment and V/Q mismatch from extensive fibrosis limit oxygen uptake despite high FiO2.