🔍 Question of the Day

Patient Profile:

• Age: 35-year-old man

• Chief Complaint: Worsening shortness of breath

History of Present Illness:

• Timeline: Worsening shortness of breath over the past 18 months. Initially noticed during hiking, now occurs even with walking.

• Associated Symptoms: Occasional mild wheezing and sputum production.

• Medical History: No significant past illnesses.

• Lifestyle Factors: Smokes 0.5 packs/day for 5 years.

 Family History: Father died young from lung and liver disease

Pulmonary Function Tests (PFTs):

• FEV1: Decreased

• FVC: Decreased

• FEV1/FVC ratio: Reduced

Correct Answer 🎯: D. Panacinar Emphysema

⚙️

Genetic Mutation in SERPINA1 Gene (AAT deficiency)

⬇

Reduced AAT production in the liver

⬇

⬇ Inhibition of neutrophil elastase in the lungs (protease-antiprotease imbalance)

⬇

Elastase activity ↑ in alveolar walls

⬇

Progressive destruction of alveoli (affects lower lobes predominantly)

⬇

Panacinar emphysema develops (uniform involvement of entire acinus)

⬇

↓ Elastic recoil of lungs

⬇

Air trapping and hyperinflation

⬇

↓ FEV1/FVC ratio (obstructive pattern on spirometry)

⬇

Symptoms: Progressive dyspnea, wheezing, sputum production

Symptoms Explained 🔧

Progressive Dyspnea

⚙ Mechanism:

Smoking + AAT deficiency → ⬇ AAT → Unopposed neutrophil elastase activity

⬇

Alveolar elastin degradation → Loss of elastic recoil → Air trapping

⬇

Hyperinflation → Increased work of breathing → Dyspnea

Mild Wheezing

⚙ Mechanism:

Elastin breakdown → Small airway collapse during expiration → Airflow obstruction

⬇

Turbulent airflow in airways → Wheezing

Sputum Production

⚙ Mechanism:

Smoking → Airway irritation and inflammation

⬇

Goblet cell hyperplasia → Increased mucus production → Sputum

Progression from Hikes to Walking

⚙ Mechanism:

⬆ Destruction of alveolar walls → Loss of surface area for gas exchange

⬇

⬇ Pulmonary compliance → Further increase in breathing effort

⬇

Symptoms worsen from exertion to daily activities

How To Approach this Question? 🏗️

Patient Symptoms

• Progressive dyspnea + mild wheezing & sputum production

⬇

🔍 Initial Diagnostic Clue: Spirometry Findings

• ⬇ FEV1, ⬇ FVC, ⬇ FEV1/FVC ratio (Obstructive pattern)

⬇

⚖ Compare Differentials Using Key Clues:

• Young age + family history of lung & liver disease → 🧠 Suggests AAT deficiency.

• Lower lobe involvement → 🧠 Consistent with panacinar emphysema (AAT deficiency).

⬇

Primary Diagnosis: Panacinar Emphysema (AAT Deficiency)

⚙ Mechanism:

• SERPINA1 mutation → ⬇ AAT production → ↑ elastase activity → alveolar destruction.

⬇

Confirmatory Diagnostic Steps:

• 🔍 Serum AAT levels → ⬇ (confirm deficiency).

• ⚙ Genetic testing → Identify SERPINA1 mutation.

⚖️ Explanation of Other Differentials

📝 Flashcards

Stay Hungry, Stay Curious!

Your Brother In This Struggle

Dr. Shoaib Ahmad

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