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🩺 MASTER CLINICAL MEDICINE COURSE

Symptom-Based Approach to Human Disease

Taught by a Senior Internal Medicine Professor

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COURSE ORIENTATION

• The symptom first (definition, pathophysiology)
• The full differential (common to life-threatening)
• How to reason from symptom to diagnosis
• Red flags, key questions, exam findings, investigations
• Mnemonics, clinical pearls, exam-relevant traps
• A clinical scenario and a question to test you

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FOUNDATIONAL FRAMEWORK: THE DIAGNOSTIC MIND

How Expert Clinicians Think

The Universal Symptom Framework (apply to EVERY symptom)

SOCRATES (for pain) + DEAD SLOW STOP (for all symptoms)

S - Site
O - Onset (sudden vs. gradual)
C - Character (quality: sharp, dull, crushing, burning)
R - Radiation
A - Alleviating / Aggravating factors
T - Timing (constant vs. intermittent, duration)
E - Exacerbating factors
S - Severity (0-10) + associated Symptoms

DEAD SLOW STOP (for systemic review):
D - Duration
E - Evolution (getting better/worse/same)
A - Associated symptoms
D - Disability caused

S - Similar episodes in the past
L - Last normal health
O - Other medical problems / medications
W - What the patient thinks is wrong

S - Social history (smoking, alcohol, occupation, travel)
T - Triggers
O - Operations/procedures
P - Pregnancy status (in women)

The Diagnostic Triad to Always Answer

1. What is the most likely diagnosis? (Bayesian thinking - base rate x clinical features)
2. What is the most dangerous diagnosis I must rule out? (Never miss)
3. What diagnosis fits ALL the features? (The unifying diagnosis)

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MODULE 1: CARDIOVASCULAR SYSTEM

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SYMPTOM 1: CHEST PAIN

1.1 Definition

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1.2 Pathophysiology of Chest Pain

• Somatic nerves (skin, parietal pleura, pericardium) - produce sharp, well-localized pain
• Visceral afferents (heart, aorta, esophagus, lungs) - produce poorly localized, deep, referred pain

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1.3 The Complete Differential Diagnosis of Chest Pain

LIFE-THREATENING (Rule Out First - "The Six Killers"):

ACS, PE, Tension pneumothorax, Tamponade, aortic disseCtion, Esophageal rupture

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CARDIOVASCULAR (Non-Immediately-Life-Threatening):

• Stable Angina - Predictable exertional chest tightness, relieved by rest/nitrates within 5 min
• Myocarditis - Young patient, viral prodrome, chest pain + dyspnea + arrhythmia
• Pericarditis - Sharp, pleuritic pain, worse lying flat, better leaning forward; friction rub on exam
• Hypertrophic Cardiomyopathy (HCM) - Young athlete, exertional chest pain, family history of sudden death
• Aortic Stenosis - Exertional angina + syncope + dyspnea (SAD triad)
• Prinzmetal/Vasospastic Angina - Pain at rest (often 2-6 AM), ST elevation on ECG during episode, no fixed stenosis
• Cocaine-induced vasospasm - History of cocaine use, young patient with MI

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PULMONARY:

• Pleuritis - Sharp, well-localized, worsens with breathing/coughing; pleuritic friction rub
• Pneumonia - Pleuritic pain + fever + productive cough + consolidation on CXR
• Pulmonary Hypertension - Exertional chest pain + progressive dyspnea + right heart strain

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GASTROINTESTINAL:

• GERD - Burning retrosternal pain, worse after meals/lying down, relieved by antacids; can mimic angina and even responds to nitrates (both relax smooth muscle!)
• Esophageal Spasm - Severe substernal pain, may radiate to back, can be relieved by nitrates - a classic ACS mimic
• Peptic Ulcer / Gastritis - Epigastric pain, often postprandial or nocturnal
• Biliary Colic - Right upper quadrant + epigastric pain after fatty meals, can radiate to right shoulder

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MUSCULOSKELETAL:

• Costochondritis (Tietze syndrome) - Reproducible tenderness on palpation of costochondral junctions (2nd-5th ribs most common). Key teaching point: chest wall tenderness does NOT rule out ACS - both can coexist.
• Cervical/Thoracic Radiculopathy - Dermatomal pain, shooting, worsened by neck movement
• Rib fracture - Trauma history, localized, exquisitely tender

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OTHER:

• Herpes Zoster - Pain precedes rash by 2-7 days, dermatomal distribution, burning/electric quality
• Anxiety/Panic Attack - Atypical pain, diaphoresis, palpitations, derealization; diagnosis of exclusion only after ruling out organic causes
• Anemia - Severe anemia causes angina by O2 supply-demand mismatch even with normal coronaries
• Thyrotoxicosis - Increased myocardial demand can cause ischemia
• Pancoast Tumor - Apical lung tumor causing shoulder/arm pain + Horner syndrome + SVC syndrome

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1.4 Red Flag Symptoms - Seek Urgent Evaluation

1. Pain maximal at onset (dissection until proven otherwise)
2. Associated diaphoresis, nausea/vomiting
3. Radiation to both arms or jaw
4. Syncope or near-syncope with the pain
5. Hemodynamic instability (hypotension, HR >120)
6. New murmur with chest pain
7. Oxygen saturation <94%
8. Unequal blood pressures in both arms (>20 mmHg difference - dissection)
9. Pleuritic pain + tachycardia + risk factors for PE (immobility, recent surgery, malignancy, OCP use)
10. Pain after forceful vomiting (Boerhaave)

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1.5 Key History Questions

• "Did the pain come on suddenly or gradually?" (Sudden = dissection, pneumothorax, PE)
• "What were you doing when it started?" (Exertion = ACS, rest/sleep = vasospasm, after vomiting = Boerhaave)

• "Describe the pain in your own words." (Let them speak - don't lead)
• "Is it crushing? Sharp? Burning? Tearing?"

• "Does it go anywhere - arm, jaw, back, shoulder?"
• Left arm/jaw = cardiac; back (interscapular) = dissection; right shoulder = biliary; ipsilateral shoulder = diaphragmatic irritation/pericarditis

• Dyspnea, diaphoresis, nausea (ACS)
• Fever, cough (pneumonia, pericarditis)
• Leg swelling, recent travel (PE)
• Heartburn, regurgitation, dysphagia (GI)
• Recent viral illness (myocarditis, pericarditis)

• Relief with nitrates: ACS and esophageal spasm both respond
• Relief leaning forward: pericarditis
• Worse lying flat: GERD, pericarditis
• Reproducible on palpation: musculoskeletal (but never rule out ACS on this alone)
• Worse with breathing: pleuritis, pericarditis, musculoskeletal

• Cardiac: age, sex, diabetes, hypertension, dyslipidemia, smoking, family history, obesity
• PE: Wells criteria (immobility, recent surgery/fracture, malignancy, prior DVT/PE, tachycardia, signs of DVT, alternative diagnosis less likely)
• Dissection: Marfan syndrome, bicuspid aortic valve, uncontrolled hypertension, cocaine use, pregnancy, history of instrumentation/cardiac surgery

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1.6 Physical Examination

• Blood pressure both arms (>20 mmHg difference = dissection)
• Heart rate and rhythm
• Oxygen saturation
• Respiratory rate
• Temperature (fever suggests infection/inflammation)

• JVP - Elevated in tamponade, tension pneumothorax, right heart failure, SVCO
• Pulsus paradoxus (>10 mmHg fall in SBP with inspiration) = tamponade, severe asthma/COPD
• Murmurs:
  • New aortic regurgitation = dissection involving aortic root
  • Pericardial friction rub = pericarditis (pathognomonic - 3 components: atrial systole, ventricular systole, ventricular diastole)
  • Mitral regurgitation murmur = papillary muscle rupture (post-MI emergency)
• S3 gallop = heart failure, volume overload
• S4 gallop = stiff/non-compliant ventricle (LVH, ACS)

• Absent breath sounds unilaterally = pneumothorax, pleural effusion, hemothorax
• Crackles (rales) = pulmonary edema, pneumonia
• Friction rub = pleuritis
• Tracheal deviation away from side = tension pneumothorax (trachea pushed away from the high-pressure side)
• Tracheal deviation toward side = lung collapse/atelectasis (trachea pulled toward collapsed lung)

• Epigastric tenderness = GI cause
• Right upper quadrant tenderness = biliary, liver

• Leg swelling + calf tenderness = DVT (PE workup)
• Subcutaneous emphysema in neck = Boerhaave, tension pneumothorax
• Vesicular rash in dermatomal distribution = herpes zoster

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1.7 Clinical Reasoning Algorithm for Chest Pain

CHEST PAIN
    |
    v
UNSTABLE? (hypotension, diaphoresis, severe distress, SaO2 <94%)
    |
   YES → Activate emergency protocol → ECG in <10 min, IV access, O2, monitors
    |
   NO → Continue structured assessment
    |
    v
CHARACTERIZE THE PAIN
    |
    +-- CRUSHING/PRESSURE + radiation + diaphoresis → ACS pathway
    |       → 12-lead ECG immediately
    |       → If STEMI: cath lab activation
    |       → If NSTEMI/UA: troponins, risk stratify (TIMI/GRACE score)
    |
    +-- TEARING/RIPPING, maximal at onset, radiates to back → DISSECTION pathway
    |       → CT aortography stat
    |       → Avoid anticoagulation until ruled out
    |
    +-- PLEURITIC (sharp, worse with breathing) + dyspnea + tachycardia → PE pathway
    |       → Wells score → If high probability: CT-PA or V/Q scan
    |       → D-dimer only if low probability
    |
    +-- PLEURITIC + friction rub + fever/viral prodrome → PERICARDITIS
    |       → ECG (diffuse saddle-shaped ST elevation, PR depression)
    |       → Echo to rule out effusion
    |
    +-- REPRODUCIBLE ON PALPATION + no other features → MUSCULOSKELETAL
    |       → But ALWAYS get ECG + troponin first in appropriate risk patient
    |
    +-- BURNING + postprandial + relieved by antacid → GI (GERD, esophageal)
            → Trial of PPI; upper endoscopy if red flags

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1.8 Investigations and Why You Order Them

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1.9 Comparative Table: The 5 Most Common Serious Causes

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1.10 Important Mnemonics

Morphine, Oxygen (if SaO2 <90%), Nitrates, Aspirin (Modern note: Morphine is now used cautiously - evidence from CRUSADE registry suggests harm in NSTEMI; prefer IV nitrates for pain relief)

Cigarette smoking, Age (>45M / >55F), Sex (male), HTN, Diabetes, Abnormal lipids, Diet/obesity

Diffuse (not regional) ST elevation + PR depression = pericarditis Regional ST elevation = ACS (follow coronary artery territory)

Marfan, Aortic aneurysm history, Related connective tissue disease, Family history, AORTic valve (bicuspid), Nothing on other tests Hypertension, Instrumentation, Trauma, Syphilis

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1.11 Clinical Pearls and Pitfalls

1. Women, diabetics, and elderly patients have atypical ACS presentations. They may present with fatigue, nausea, jaw pain, or epigastric pain without classic chest pressure. The NRMI registry showed women were twice as likely to present without chest pain and had higher in-hospital mortality as a result of delayed diagnosis.
2. The ECG can be normal in 50% of NSTEMI/UA presentations on the first ECG. Serial ECGs at 15-30 minute intervals are mandatory if the clinical suspicion is high.
3. Nitroglycerin relieving pain does NOT confirm angina - esophageal spasm also responds to nitrates.
4. A positive D-dimer is not a diagnosis of PE. It is elevated in pregnancy, infection, malignancy, post-surgery, and many inflammatory states. Only use D-dimer to RULE OUT PE in low-probability patients.
5. Pulsus paradoxus >10 mmHg with elevated JVP and muffled heart sounds = cardiac tamponade. Pericardiocentesis is lifesaving.
6. Wellens syndrome (biphasic or deeply inverted T-waves in V2-V3 during chest-pain-free period) = critical LAD stenosis. This patient is about to have a massive anterior STEMI. Do NOT stress test - go to cath lab.

• Attributing chest pain to "musculoskeletal" based on tenderness alone without ECG/troponin
• Missing dissection because the BP is normal or the ECG looks like STEMI (dissection can occlude the RCA)
• Giving anticoagulation for STEMI before ruling out dissection when the presentation is atypical
• Discharging a patient with chest pain and a normal first troponin without a 3-hour repeat troponin

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1.12 Real-Life Clinical Scenario

Patient: Mr. SK, 58-year-old male, smoker, diabetic, hypertensive. Presents to the ED at 3 AM with 2 hours of "indigestion" and sweating. He has taken antacids with no relief. He denies "chest pain" but says his chest feels "heavy." He is slightly diaphoretic. ECG shows 2mm ST depression in leads V4-V6 and I, aVL. Troponin-I is 0.04 ng/mL (normal <0.04).

• Why might he call this "indigestion"?
• Is his troponin "normal"?
• What is the next step?
• What scoring system would you use?
• What is the most dangerous decision error you could make here?

Analysis: This is a classic NSTEMI presentation. Diabetics commonly have atypical symptoms (autonomic neuropathy blunts typical pain perception). The troponin is at the upper limit of normal - a "borderline" value that requires a 3-hour repeat. The ST depressions in the lateral leads (V4-V6, I, aVL) confirm posterior/lateral ischemia. Apply the TIMI or GRACE score to risk-stratify. Do NOT discharge him. The most dangerous error: attributing symptoms to GERD and discharging without a repeat troponin.

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SYMPTOM 2: DYSPNEA (Shortness of Breath)

2.1 Definition

• Harrison's 22e definition: "Dyspnea is a term used to characterize a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity."
• The MRC Dyspnea Scale grades 0 (none except strenuous exercise) to 4 (too breathless to leave the house)

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2.2 Pathophysiology

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2.3 Complete Differential Diagnosis of Dyspnea

• Left ventricular failure (systolic/diastolic dysfunction) - the most common cause of exertional dyspnea in adults over 50
• ACS (acute pulmonary edema = "flash pulmonary edema")
• Valvular disease (aortic stenosis, mitral regurgitation, mitral stenosis)
• Cardiac arrhythmia (AF, SVT - reduced cardiac output)
• Cardiac tamponade
• Cardiomyopathy (dilated, hypertrophic, restrictive)

• Asthma - episodic, reversible, triggered by allergens/exercise/cold; often nocturnal
• COPD - chronic progressive, smoking history, air trapping, barrel chest
• Bronchiectasis - chronic productive cough + dyspnea
• Tracheal stenosis/foreign body (consider in sudden onset)

• Pneumonia
• Interstitial Lung Disease (ILD) - progressive exertional dyspnea, dry cough, "velcro" crackles, clubbing
• Pulmonary edema (cardiogenic or non-cardiogenic/ARDS)
• Lung cancer

• Pulmonary Embolism (acute) - sudden onset, pleuritic pain, tachycardia
• Pulmonary Arterial Hypertension (PAH) - progressive exertional dyspnea, RV failure

• Pleural effusion - dullness to percussion, absent breath sounds
• Pneumothorax - sudden, pleuritic, tracheal deviation (if tension)

• Anemia - fatigue + dyspnea on exertion, pallor; O2 carrying capacity reduced
• Metabolic acidosis (DKA, lactic acidosis, renal failure) - Kussmaul respiration (deep, sighing)
• Neuromuscular (myasthenia gravis, Guillain-Barré, ALS, phrenic nerve palsy) - paradoxical breathing, diaphragm dysfunction
• Deconditioning/Obesity
• Thyrotoxicosis - high cardiac output state
• Psychogenic/hyperventilation - dyspnea at rest, carpopedal spasm, normal O2 sat, tingling in extremities, responds to breathing into bag/reassurance
• Post-COVID syndrome - a growing cause, multi-mechanism

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2.4 Critical Differentiator: ACUTE vs. CHRONIC Dyspnea

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2.5 Red Flags in Dyspnea

1. Stridor (high-pitched inspiratory sound) = upper airway obstruction - anaphylaxis, foreign body, epiglottitis, croup - airway emergency
2. SaO2 <90% at rest
3. Accessory muscle use + tripod positioning
4. Cyanosis (central or peripheral)
5. Altered consciousness with dyspnea = impending respiratory failure
6. Sudden onset at rest = PE, pneumothorax, APE
7. Hemoptysis + dyspnea = PE, malignancy, vasculitis
8. Bilateral leg edema + dyspnea = CHF, PE
9. Cannot speak in full sentences
10. Silent chest in asthma = pre-terminal - bronchospasm so severe no airflow is moving

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2.6 Key Differentiator - Orthopnea vs. PND vs. Platypnea

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2.7 Physical Examination for Dyspnea

• Posture (tripod = obstructive lung disease)
• Color (cyanosis, pallor)
• Accessory muscle use (sternocleidomastoid, scalene)
• Paradoxical breathing (abdomen moves in on inspiration) = diaphragm weakness

• Tachycardia + hypoxia = serious pathology
• Respiratory rate >25/min = severe illness

• Wheeze (expiratory) = bronchospasm (asthma, COPD, pulmonary edema - "cardiac asthma")
• Fine crackles = pulmonary edema, ILD, early consolidation
• Coarse crackles = consolidation, bronchiectasis
• Absent breath sounds = pneumothorax, effusion, severe obstruction
• Pleural rub = pleuritis, PE
• Bronchial breathing = consolidation (lung tissue becomes solid, conducts sound like a bronchus)

• Elevated JVP = RV failure, PE, cardiac tamponade, SVCO
• S3 gallop = LV failure
• Loud P2 = pulmonary hypertension
• Murmurs (mitral stenosis causing pulmonary edema)

• Clubbing = ILD, lung cancer, bronchiectasis, cyanotic CHD (not COPD)
• Peripheral edema = right heart failure
• DVT signs = PE

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2.8 Investigations for Dyspnea

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2.9 Mnemonic for Causes of Dyspnea: "AMPLE CARDIAC"

Anemia, Metabolic acidosis, Pneumo (thorax/monia/COPD), Left heart failure, Embolism (PE) Cardiomyopathy, Airways (asthma), Restriction (ILD/fibrosis), Diaphragm weakness, Infection, Anxiety, Cancer

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2.10 Clinical Scenario

Patient: Mrs. PM, 72-year-old woman with known hypertension and atrial fibrillation, presents at midnight with 2-hour history of extreme breathlessness. She woke from sleep gasping. She is sitting upright, cannot complete sentences. On exam: RR 32, HR 128 (irregularly irregular), BP 190/110, SaO2 84% on room air. CXR shows bilateral "bat-wing" opacities and cardiomegaly. You hear bilateral fine crackles throughout both lungs.

1. What is this?
2. What is the immediate priority (before even confirming with tests)?
3. What is the mechanism given her AF and hypertension?
4. What treatment do you give in the next 5 minutes?
5. What are 3 triggers you should look for?

Analysis: This is Acute Pulmonary Edema (APO) / Acute Decompensated Heart Failure. The uncontrolled AF (tachycardia reduces diastolic filling time, worsening LV function) combined with hypertensive crisis has precipitated APE.

Immediate management (LMNOP): Lasix (IV furosemide 40-80mg) + Morphine (low dose, cautiously) + Nitrates (IV GTN if BP allows) + Oxygen (high-flow, consider CPAP/NIV) + Propped up (sit upright)

Triggers to find (6 Hs): Hypertension (uncontrolled), High output (anemia, thyroid), Heart (new MI, arrhythmia), Holiday (dietary salt excess), Heroin/NSAID (fluid retention drugs), Heart block worsened

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COURSE ROAD MAP

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🧪 SELF-ASSESSMENT QUESTIONS (Module 1)

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📌 SPACED REPETITION REMINDERS (To be tested next session)

• The "6 Killers" of chest pain without prompting
• The ECG criteria that distinguish pericarditis from STEMI
• The Wells score components for PE
• The MRC dyspnea grade definitions

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SOURCES USED IN THIS MODULE

• Harrison's Principles of Internal Medicine, 22nd Edition (2025) - Dyspnea chapter (Ch. 39), referenced from the textbook library
• Washington Manual of Medical Therapeutics - Differential Diagnosis of Chest Pain table
• Symptom to Diagnosis: An Evidence-Based Guide, 4th Edition - Diagnostic reasoning framework
• Frameworks for Internal Medicine - Key points on dyspnea pathophysiology
• Braunwald's Heart Disease and Fuster and Hurst's The Heart - Cardiovascular pathophysiology

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🫁 MODULE 2: RESPIRATORY SYSTEM

Symptom-Based Approach

• The 6 Killers of chest pain: ACS, PE, Tension pneumothorax, Tamponade, disseCtion, Esophageal rupture (APT-TCE)
• Pericarditis ECG: diffuse ST elevation + PR depression (not regional, not reciprocal changes)
• Troponin timing: rises 3-6h, peaks 24h, normalizes 5-14 days

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SYMPTOM 3: COUGH

3.1 Definition and Classification

• Harrison's 22e: Chronic cough is one of the most common presenting complaints in outpatient medicine.

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3.2 Pathophysiology of Cough

RECEPTORS (afferent) → AFFERENT NERVE → COUGH CENTER → EFFERENT PATHWAY

Cough receptors: Located in larynx, carina (most sensitive), 
                 bronchi, alveoli, pericardium, esophagus, stomach
                 (explains why GERD → cough without heartburn)

Afferent nerves: Vagus nerve (CN X) carries most signals
                 Some via trigeminal, phrenic, glossopharyngeal

Cough center: Brainstem (medulla) + voluntary cortical override

Efferent pathway: Recurrent laryngeal nerve (closes glottis) + 
                  phrenic/intercostal nerves (generate expulsive force)

• Mechanical: Secretions, foreign body, tumor compression
• Inflammatory: Cytokines lower the cough threshold (explains why post-viral cough persists weeks)
• Chemical: Acid (GERD), ACE inhibitor (bradykinin accumulation)
• Thermal: Cold air (exercise-induced asthma, cold-air testing)
• Neurogenic sensitization: Chronic cough hypersensitivity syndrome - central and peripheral sensitization without ongoing stimulus

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3.3 The Three Most Common Causes of Chronic Cough

GERD (gastroesophageal reflux disease) Asthma (including cough-variant asthma) Postnasal drip / Upper Airway Cough Syndrome (UACS)

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3.4 Complete Differential Diagnosis of Cough

• Viral URTI (rhinovirus, coronavirus, influenza) - most common cause of acute cough globally
• Acute bronchitis (usually viral; 95% do not need antibiotics)
• COVID-19 / influenza - fever, myalgia, dyspnea
• Pneumonia - fever, productive cough, consolidation
• Acute left ventricular failure - "cardiac cough," pink frothy sputum, nocturnal
• Foreign body aspiration - sudden onset, especially in children/elderly
• Inhalation injury - chemical, smoke

• Post-infectious/postviral cough (most common) - residual airway inflammation
• Pertussis (Bordetella pertussis) - paroxysmal cough + inspiratory "whoop" + post-tussive vomiting; more common in adults than once thought
• Mycoplasma or Chlamydophila pneumonia - atypical, persistent, non-productive

• Rhinitis (allergic, vasomotor), sinusitis, adenoids
• Symptoms: sensation of drip down throat, throat clearing, nasal symptoms
• Exam: "cobblestoning" of posterior pharynx, mucus on posterior wall

• Classic asthma has wheeze + dyspnea + cough
• Cough-variant asthma: cough is the ONLY symptom - no wheeze, no dyspnea
• Diagnosis: methacholine challenge test (if negative, excludes asthma with high sensitivity)
• Key trigger: cold air, exercise, allergens, NSAIDs, beta-blockers

• Cough can occur without heartburn (extraesophageal manifestations)
• Mechanism: micro-aspiration of gastric contents + vagal reflex via esophageal acid stimulation
• Test: 24-hour pH monitoring (gold standard); empiric PPI trial often first

• Switch to ARB (no bradykinin accumulation with ARBs)

• Morning cough, productive, in a smoker >40 years old
• Definition of chronic bronchitis: productive cough >3 months/year for >2 consecutive years
• CXR may be normal; spirometry shows obstruction

• Dry, irritative cough + progressive dyspnea + bilateral "velcro" crackles at bases
• HRCT shows honeycombing (UIP pattern) or ground-glass opacities

• Change in character of chronic cough in a smoker is lung cancer until proven otherwise
• Associated: hemoptysis, weight loss, clubbing, Horner syndrome (Pancoast)

• Chronic productive cough of large amounts of purulent sputum ("cupfuls")
• Three-layer sputum on standing (mucus on top, watery middle, purulent bottom)
• Associated: recurrent chest infections, clubbing
• Causes: post-TB, cystic fibrosis, primary ciliary dyskinesia, immunodeficiency

• Cough + sputum eosinophilia without bronchial hyperresponsiveness
• Responds to inhaled corticosteroids

• Increasingly recognized; central sensitization of cough reflex pathways
• No identifiable trigger; often triggered by talking, laughing, cold air

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3.5 Red Flags in Cough - Must Not Miss

1. Hemoptysis - always needs investigation (see Symptom 4 below)
2. Weight loss + night sweats + chronic cough = TB or malignancy until proven otherwise
3. Cough in a smoker >40 years old that changes character = lung cancer
4. Stridor with cough = upper airway compromise
5. Fever + productive cough + hypoxia = pneumonia - assess severity (CURB-65)
6. New cough in immunocompromised patient = Pneumocystis jirovecii pneumonia (PJP), fungal, atypical
7. Paroxysmal cough with post-tussive vomiting in adults = pertussis (underdiagnosed)
8. Cough after a meal + recurrent chest infections = aspiration (neuromuscular disease, esophageal dysmotility)

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3.6 Key History Questions for Cough

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3.7 Physical Examination for Cough

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3.8 Algorithm for Chronic Cough

CHRONIC COUGH (>8 weeks)
        |
        v
CXR + Spirometry (FEV1/FVC, bronchodilator reversibility)
        |
    +---+---+
    |       |
ABNORMAL   NORMAL
    |           |
Directed        Smoking? On ACE-I?
workup          |
(TB/cancer/     YES → Stop ACE-I / smoking cessation
ILD/COPD)       NO
                |
                Treat for BIG THREE empirically:
                1. Trial of nasal steroid + antihistamine (for UACS) x 2-4 weeks
                2. Trial of high-dose PPI (for GERD) x 4-8 weeks
                3. Spirometry + bronchodilator test / methacholine challenge (for asthma)
                |
                Still not resolved?
                |
                HRCT chest → Bronchoscopy → 24h pH monitoring
                → Consider NAEB (sputum eosinophils) → Chronic cough hypersensitivity

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3.9 Investigations

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3.10 Mnemonics

GERD, Asthma (cough-variant), Smoking/Bronchitis, Postnasal drip (UACS), Eosinophilic bronchitis, Drugs (ACE inhibitor)

Pink frothy = pulmonary edema; Rust = pneumococcal; Green/yellow = infection; Yellow = purulent/eosinophilic; Currant jelly = Klebsiella; Kaolin/white = asthma/casts

Abscess (lung), Bronchiectasis, Carcinoma of lung, Diffuse ILD, Endocarditis (infective) (Also: congenital cyanotic CHD, inflammatory bowel disease, cirrhosis)

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SYMPTOM 4: HEMOPTYSIS

4.1 Definition and Classification

• Hematemesis (blood from GI tract - dark, coffee-ground, mixed with food, preceded by nausea, pH acidic, no bubbles)
• Pseudohemoptysis (blood from upper airway/nasopharynx, no respiratory symptoms)

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4.2 Pathophysiology

• Pulmonary arteries (low pressure, ~25 mmHg systolic) - gas exchange
• Bronchial arteries (systemic pressure, ~120 mmHg) - airway nutrition

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4.3 Complete Differential Diagnosis of Hemoptysis

1. Acute bronchitis / URTI (most common overall) - blood-streaked sputum, self-limited
2. Pneumonia - rust-colored or blood-streaked; associated fever, consolidation
3. Bronchiectasis - recurrent hemoptysis, copious sputum
4. Tuberculosis - the classic cause; cavitating upper lobe disease; "Rasmussen's aneurysm" (mycotic aneurysm of pulmonary artery in a TB cavity - catastrophic)
5. Lung cancer - streaking or frank hemoptysis; especially squamous cell carcinoma (central, cavitating)
6. Lung abscess - foul-smelling sputum + hemoptysis + cavitation on CXR

• <40 years: Infection (TB, bronchiectasis, lung abscess), mitral stenosis, AVM, vasculitis
• >40-45 years with smoking history: Lung cancer is the primary concern

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4.4 Red Flags in Hemoptysis

1. >300 mL in 24 hours = massive hemoptysis - emergency airway management
2. Hemoptysis + weight loss + smoking history >40 yrs = malignancy until proven otherwise
3. Hemoptysis + hematuria = pulmonary-renal syndrome (Goodpasture, GPA, SLE)
4. Hemoptysis + cavitary upper lobe lesion = TB (especially in immigrant, HIV+, immunocompromised)
5. New hemoptysis in a patient on anticoagulation - does NOT mean the anticoagulation is the cause; must find the underlying lesion
6. Hemoptysis + telangiectasias + family history = HHT
7. Hemoptysis + hemodynamic instability = bronchial artery embolization urgently

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4.5 Immediate Management of Massive Hemoptysis

MASSIVE HEMOPTYSIS PROTOCOL:

1. AIRWAY: Intubate early (before total airway flooding)
   → Large bore ETT (≥8mm) to allow bronchoscopy
   → Position: bleeding lung DOWN (dependent) to protect the good lung

2. IV ACCESS: Two large-bore IVs + type and crossmatch

3. LOCALIZE: CXR, CT chest, bronchoscopy
   → Bronchoscopy: localizes bleeding AND can be therapeutic
     (endobronchial tamponade, topical epinephrine, argon plasma coagulation)

4. DEFINITIVE:
   → Bronchial Artery Embolization (BAE) = first-line definitive therapy
     (90%+ success rate for stopping bleeding)
   → Surgery (lobectomy) if BAE fails or technically impossible
   → In TB cavitary disease: consider cavernotomy

5. Treat underlying cause (antibiotics for TB/pneumonia/abscess)

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4.6 Investigations for Hemoptysis

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SYMPTOM 5: WHEEZE

5.1 Definition

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5.2 Complete Differential Diagnosis of Wheeze

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5.3 The Great Imitators of Asthma

• Older age, history of cardiac disease
• Elevated JVP, S3, bilateral fine crackles
• CXR: cardiomegaly + bilateral effusions + Kerley B lines
• BNP/NT-proBNP elevated
• Responds to IV furosemide + nitrates, NOT bronchodilators alone

• Young women, often with psychological stress
• Inspiratory stridor, not expiratory wheeze
• Spirometry: flattening of the INSPIRATORY limb of flow-volume loop (vs. asthma: EXPIRATORY limb)
• Normal methacholine challenge
• Does NOT respond to bronchodilators; treated with speech therapy, breathing exercises

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SYMPTOM 6: STRIDOR

6.1 Definition and Pathophysiology

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6.2 Differential Diagnosis of Stridor by Age

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THE BIG COMPARISON: ASTHMA vs. COPD vs. CARDIAC ASTHMA

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PLEURAL EFFUSION: A Complete Approach

Light's Criteria (You MUST know this)

1. Pleural fluid protein / Serum protein > 0.5
2. Pleural fluid LDH / Serum LDH > 0.6
3. Pleural fluid LDH > 2/3 upper limit of normal for serum LDH

• Serum albumin - Pleural fluid albumin > 1.2 g/dL = TRANSUDATE (overrules Light's)

Transudates vs. Exudates

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GOLD 2026 COPD CLASSIFICATION (Exam-Essential, Updated)

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CLINICAL SCENARIO - RESPIRATORY MODULE

Patient: Mr. RK, 52-year-old ex-smoker (30 pack-years, stopped 2 years ago). Presents with 3-month history of progressively worsening dry cough. He denies fever, hemoptysis, or weight loss. He is on lisinopril for hypertension and is otherwise well. CXR is reported as "normal." Spirometry shows FEV1/FVC = 0.72, FEV1 = 88% predicted. Post-bronchodilator FEV1/FVC = 0.71 (not significant reversibility).

1. What is the most likely cause of his cough, and why is this the first thing you should address?
2. His spirometry shows a mild fixed obstruction. How does this change your thinking?
3. After stopping his lisinopril for 3 weeks, his cough persists. What do you do now?
4. What test would confirm or exclude cough-variant asthma in this patient?
5. At what point would you order a CT chest, and why?

Analysis:

1. ACE inhibitor (lisinopril) cough is the first thing to address - it affects ~10-15% of users, is the most actionable cause, and simply requires switching to an ARB (e.g., losartan). Always do this FIRST before expensive investigations.
2. The mild fixed obstruction on spirometry without significant reversibility is more consistent with early COPD (GOLD 1) or his smoking history than asthma. However, this does not explain the 3-month dry cough.
3. Once ACE-I cough is excluded (cough persists >4 weeks after stopping), proceed through the BIG THREE: assess for UACS (nasal steroid trial), GERD (PPI trial), then asthma (methacholine challenge).
4. Methacholine challenge test - if negative, excludes asthma with high sensitivity (~99% NPV). He would need normal spirometry for this - with FEV1 88%, he can safely undergo this.
5. CT chest is ordered if: cough persists despite treating all three BIG THREE causes, any red flag emerges (hemoptysis, weight loss, change in sputum), or baseline CXR had any subtle abnormality. In a 52-year-old ex-smoker, low-dose CT chest is also part of lung cancer screening (per USPSTF criteria: 50-80 years, ≥20 pack-year history, current or quit within 15 years).

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🧪 MODULE 2 SELF-ASSESSMENT QUESTIONS

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📌 SPACED REPETITION REMINDERS FOR NEXT SESSION

• The 6 Killers of chest pain (from Module 1) without prompting
• Light's criteria thresholds (from this module) from memory
• The three most common causes of chronic cough

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SOURCES USED - MODULE 2

• Harrison's Principles of Internal Medicine, 22nd Edition (2025) - Chapters on Cough (Ch. 40) and Dyspnea (Ch. 39)
• Frameworks for Internal Medicine - Hemoptysis key points and mitral stenosis hemoptysis mechanism
• Fishman's Pulmonary Diseases and Disorders - Hemoptysis causes (Table 27-10), pathophysiology
• Symptom to Diagnosis: An Evidence-Based Guide, 4th Edition - Light's criteria with sensitivity/specificity data
• ROSEN's Emergency Medicine - Stridor, upper airway obstruction, epiglottitis
• GOLD 2026 COPD Report - Current classification and diagnostic criteria
• Miller's Anesthesia - Pediatric airway obstruction and stridor

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• Abdominal pain (the most complex symptom in medicine)
• Nausea and vomiting
• Diarrhea (acute and chronic)
• Constipation
• Gastrointestinal bleeding (upper and lower)
• Including the complete approach to the acute abdomen, peritonitis, and obstruction