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Hemoptysis in a 55-Year-Old Male: Causes, Diagnosis & Management

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Definition & Initial Framing

• Pseudohemoptysis: blood from oropharynx, nasopharynx, or sinuses
• Hematemesis: vomiting blood from the GI tract (usually dark, mixed with food, preceded by nausea)

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Causes of Hemoptysis

Classified by Frequency / Category

In a 55-year-old male smoker, the top three to prioritize are: Lung carcinoma, TB/post-TB sequelae, and Chronic bronchitis/bronchiectasis.

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Approach to Diagnosis

Step 1 — History

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Step 2 — Physical Examination

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Step 3 — Investigations

Immediate (All Patients)

Second Line (Based on Initial Results)

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Diagnostic Algorithm

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Management

A. Non-Massive Hemoptysis (Majority of Cases)

1. Treat the underlying cause (e.g., antibiotics for infection, antitubercular therapy for TB)
2. Investigate fully — CT chest is mandatory; bronchoscopy if CT equivocal or mass suspected
3. Risk stratify — even "minor" hemoptysis in a 55-year-old male must have malignancy excluded
4. Avoid cough suppressants that could cause clot retention
5. Follow-up CXR / CT in 6–8 weeks if initial workup inconclusive

B. Massive Hemoptysis (Life-Threatening Emergency)

Massive = >600 mL/24h or any amount causing hemodynamic instability or airway compromise. Death is from asphyxiation, not exsanguination.

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Summary for This Patient

Complete Answers — Edema, Ascites & Effective Circulatory Volume

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Q1 (Dec 2019) — Generalized Edema + Ascites

a) Etiology, History & Physical Examination of Generalized Edema

Etiology

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History

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Physical Examination

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b) Diagnosis and Management of Ascites

Diagnosis

• Abdomen: fullness of flanks, shifting dullness (>500 mL), fluid thrill (>1000–1500 mL), puddle sign (>150 mL)
• Umbilical eversion, hernias

SAAG Classification

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Management of Ascites (Bailey & Love, p. 1228; Harrison's 21st)

General Measures

1. Treat the underlying cause (e.g., abstain from alcohol in alcoholic cirrhosis)
2. Dietary sodium restriction: < 2 g/day (88 mmol/day) — cornerstone
3. Fluid restriction: Only if serum Na⁺ < 125 mmol/L

Pharmacological (Stepwise Diuretic Therapy)

Refractory Ascites (non-responsive to diuretics)

Spontaneous Bacterial Peritonitis (SBP) — Complication to Recognize

• Diagnose: Ascitic fluid PMN > 250 cells/mm³
• Treat: IV Cefotaxime 2g q8h × 5 days + albumin (1.5 g/kg day 1, 1 g/kg day 3)
• Prophylaxis: Norfloxacin 400 mg/day (long-term after first episode)

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Q2 (April 2016) — Effective Circulatory Volume

a) What is Effective Circulatory Volume (ECV)?

• ECV correlates with arterial fullness and determines renal sodium and water handling
• Under normal conditions, ECV ≈ effective arterial blood volume — roughly 25% of total blood volume (~700–800 mL)
• ECV is regulated by the RAAS, ADH, ANP, and renal sympathetic nerves
• ECV ≠ total body water or total ECF volume — total body Na⁺/water can be increased while ECV is perceived as low (e.g., heart failure, cirrhosis)

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b) Conditions with Increased and Decreased ECV & Management

↑ Increased ECV States

• Na⁺ and fluid restriction
• Diuretics (furosemide, thiazides, spironolactone)
• Treat underlying cause (adrenalectomy for Conn's, GCs for glomerulonephritis)
• Dialysis in refractory CKD overload

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↓ Decreased ECV States

• True depletion: IV fluid resuscitation (NS or RL), treat cause (stop GI losses, control hemorrhage)
• Heart failure: Diuretics + ACE inhibitors/ARBs + beta-blockers; treat cardiac disease
• Cirrhosis: Salt restriction, spironolactone, paracentesis with albumin; avoid nephrotoxins
• Nephrotic syndrome: Treat underlying glomerular disease, diuretics cautiously, albumin in severe cases
• Sepsis: IV fluids, vasopressors (noradrenaline), antibiotics

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Q3 (June 2015) — Pathogenesis & Clinical Features of Edema + Drugs Causing Edema

a) Pathogenesis of Edema

Net filtration = Kf [(Pc – Pi) – σ(πc – πi)]

• Pc = capillary hydrostatic pressure
• Pi = interstitial hydrostatic pressure
• πc = capillary oncotic pressure (plasma proteins, mainly albumin)
• πi = interstitial oncotic pressure
• Kf = filtration coefficient
• σ = reflection coefficient

Four Pathophysiological Mechanisms

Secondary Amplifying Mechanism: Na⁺/Water Retention

• ↓ ECV (regardless of cause) → RAAS activation → aldosterone → Na⁺ & water retention → worsens edema
• ADH release → water retention → dilutional hyponatremia in severe states

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Clinical Features of Edema

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b) Drugs Associated with Edema Formation

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Q4 (June 2014) — Transcellular Water + Pathogenesis of Anasarca

What is Transcellular Water?

• It constitutes approximately 1–2% of total body water (~1–2 L in a 70 kg adult)
• Technically considered a "third compartment" — not directly in equilibrium with plasma

• Cerebrospinal fluid (CSF)
• Synovial fluid (joint spaces)
• Pleural fluid
• Pericardial fluid
• Peritoneal/ascitic fluid
• Aqueous and vitreous humour (eye)
• Endolymph / perilymph (inner ear)
• Gastrointestinal secretions (saliva, gastric juice, bile, pancreatic juice, intestinal secretions)
• Sweat

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Pathogenesis of Anasarca in Various Disease States

1. Congestive Heart Failure (CHF)

• ↓ Cardiac output → ↓ renal perfusion → RAAS activation → Na⁺/water retention
• ↑ Venous pressure transmitted backward → ↑ capillary hydrostatic pressure
• ↑ ADH → water retention
• Result: ↑ total body Na⁺ and water, pitting edema, ascites, pleural effusions

2. Nephrotic Syndrome

• Glomerular disease → massive proteinuria (>3.5 g/day) → ↓ serum albumin
• ↓ Oncotic pressure → fluid shifts from intravascular to interstitium
• ↓ ECV (classical "underfill" theory) → RAAS activation → Na⁺ retention
• Overfill theory (in primary tubular defect): Na⁺ retention independent of albumin
• Result: Periorbital edema, ascites, pleural effusions, anasarca

3. Cirrhosis of Liver

• Portal hypertension → splanchnic vasodilation (↑ NO, prostacyclin)
• ↓ Effective arterial filling → RAAS + ADH activation → Na⁺/water retention
• ↓ Albumin synthesis by failing liver → ↓ oncotic pressure
• ↑ Portal pressure → fluid transudation into peritoneal cavity (ascites)
• Result: Ascites predominantly; peripheral edema; hyponatremia

4. Nephritic Syndrome (Acute GN)

• Immune complex deposition → glomerular inflammation → ↓ GFR
• "Overflow" mechanism: Primary renal Na⁺ retention → ↑ ECV → ↑ hydrostatic pressure
• Hypertension + oliguria + periorbital edema (less massive than nephrotic)

5. Kwashiorkor / Severe Protein Malnutrition

• Severely ↓ protein intake → ↓ albumin synthesis → ↓ oncotic pressure
• Fluid leaks into interstitium → anasarca
• Paradoxically, RAAS also activated → Na⁺ retention
• Result: Edematous malnutrition ("sugar baby" appearance)

6. Hypothyroidism (Myxedema)

• ↓ Thyroid hormones → accumulation of glycosaminoglycans (hyaluronic acid, chondroitin sulfate) in interstitium
• These are hygroscopic → bind water → non-pitting edema
• Also: ↓ cardiac output → component of cardiac edema

7. Protein-Losing Enteropathy

• GI diseases (Crohn's, Whipple's, lymphoma) → loss of protein into gut lumen
• ↓ Serum albumin → same mechanism as nephrotic syndrome

Summary Table

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Q5 (June 2014) — ECV, % Body Water, ECV in Nephritic vs Nephrotic

What is Effective Circulatory Volume?

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What Percentage of Body Water is in the ECV Compartment?

Body Fluid Distribution (Standard Reference)

• ECV is functionally equivalent to the effective arterial blood volume, which is approximately 25–33% of plasma volume, or roughly ~700–800 mL in a 70 kg adult
• As a fraction of TBW: ECV ≈ ~1.5–2% of TBW (or ~25% of plasma volume)

Key point: ECV is not a measurable anatomical volume — it is a functional concept defined by what baroreceptors sense.

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ECV in Nephritic Syndrome vs. Nephrotic Syndrome

Pathophysiology Comparison Diagram

NEPHRITIC:                              NEPHROTIC:
↓ GFR (inflammation)                   ↓ Oncotic pressure (proteinuria)
    ↓                                        ↓
Na⁺ + H₂O retention                  Fluid → interstitium
    ↓                                        ↓
↑ ECV (volume overload)               ↓ Plasma volume (↓ ECV)
    ↓                                        ↓
Hypertension, raised JVP             RAAS activated → Na⁺ retention
Periorbital edema                     Massive edema, ascites, anasarca

Algorithm for Evaluation of Suspected Dysphagia

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Step 1 — Confirm It Is Dysphagia

• Odynophagia — painful swallowing (not difficulty)
• Globus sensation — constant feeling of a lump in the throat, not related to swallowing
• Phagophobia — fear of swallowing (psychiatric)

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Step 2 — Localise: Oropharyngeal vs. Esophageal

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Step 3 — Diagnostic Algorithm

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Branch A — Oropharyngeal Dysphagia

Sub-classify: Structural vs. Propulsive (Neuromuscular)

Structural Causes

Propulsive (Neurogenic) Causes

Investigations for Oropharyngeal Dysphagia

1. Videofluoroscopic swallow study (modified barium swallow) — procedure of choice; evaluates all phases of swallowing in real time
2. Fiberoptic endoscopic evaluation of swallowing (FEES) — bedside, no radiation, excellent for aspiration detection
3. Otolaryngoscopy — direct visualisation of pharynx and larynx
4. Neurological evaluation — MRI brain/brainstem, nerve conduction studies, EMG
5. Manometry — rarely needed; used when cricopharyngeal dysfunction suspected

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Branch B — Esophageal Dysphagia

Sub-classify by Bolus Type and Pattern

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Structural (Mechanical) Causes

Motility (Propulsive) Causes

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Investigations for Esophageal Dysphagia

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Summary Algorithm

DYSPHAGIA
    │
    ├─ Oropharyngeal (transfer dysphagia, neck, immediate, liquids worse)
    │       │
    │       ├─ Structural → Videofluoroscopic swallow study
    │       │               + ENT evaluation + CT neck
    │       │
    │       └─ Neuromuscular → Neurological workup (MRI brain)
    │                          + FEES + EMG/NCS
    │
    └─ Esophageal (substernal, 2–10 sec after swallow)
            │
            ├─ Solids ONLY → Mechanical obstruction
            │   ├─ Progressive + weight loss → OGD + CT (rule out cancer)
            │   ├─ Intermittent, no weight loss → Barium (ring/web) + OGD
            │   └─ Young + atopy + food impaction → OGD + biopsy (EoE)
            │
            └─ Solids + Liquids → Motility disorder
                ├─ Regurgitation + weight loss → Barium + HRM (achalasia)
                ├─ Chest pain + intermittent → HRM (spasm/jackhammer)
                └─ Raynaud's + GERD → HRM (scleroderma)

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Key Clinical Pearls

• Upper endoscopy is the single most useful test for esophageal dysphagia (Harrison's, p. 1209)
• Videofluoroscopy is the procedure of choice for oropharyngeal dysphagia
• Manometry is reserved for when endoscopy and barium are normal (motility disorders)
• Any progressive dysphagia with weight loss in a patient >50 years = malignancy until proven otherwise
• Dysphagia to both solids and liquids from the start always indicates a motility disorder, never a structural one

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Harrison's Chapter 46 — Diarrhoea: Point-wise Summary

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1. DEFINITIONS

• Diarrhoea: Passage of abnormally liquid or unformed stools at increased frequency; stool weight >200 g/day in adults on a Western diet
• Acute diarrhoea: < 2 weeks
• Persistent diarrhoea: 2–4 weeks
• Chronic diarrhoea: > 4 weeks

Distinguish from:

• Pseudodiarrhoea: Frequent passage of small volumes (<200 g/day) of stool — seen in IBS, proctitis, rectal neoplasm; urgency with tenesmus
• Faecal incontinence: Involuntary passage of rectal contents — neurological or sphincter pathology; not true diarrhoea

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2. ACUTE DIARRHOEA

A. Aetiology

Infectious (Most Common)

Non-Infectious

• Drugs: antibiotics, laxatives, antacids (Mg-containing), colchicine, NSAIDs, metformin, digoxin
• Food allergy / intolerance
• Ischaemic colitis
• Diverticulitis
• First presentation of IBD

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B. Evaluation of Acute Diarrhoea

Step 1 — Identify patients needing investigation (most resolve spontaneously):

• Profuse watery diarrhoea with signs of dehydration
• Passage of many small-volume bloody stools
• Temperature >38.5°C
• Duration >48 hours without improvement
• Severe abdominal pain
• Elderly (>70 years) or immunocompromised
• Recent antibiotic use (C. difficile)
• Hospital-acquired or nosocomial diarrhoea
• Recent travel to endemic area

Step 2 — Investigations

• Stool routine & microscopy: WBCs (invasive), RBCs, ova, cysts, parasites
• Stool culture & sensitivity
• C. difficile toxin (A + B PCR or EIA) if antibiotic-associated
• Stool for rotavirus / norovirus antigen (in outbreak settings)
• CBC: leucocytosis (bacterial), eosinophilia (parasitic)
• Electrolytes, renal function: dehydration assessment
• Sigmoidoscopy/colonoscopy: if bloody diarrhoea persists or C. difficile suspected but toxin negative

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C. Management of Acute Diarrhoea

1. Rehydration (Most Important)

• Mild–moderate: Oral Rehydration Solution (ORS) — WHO formula: Na 75, K 20, Cl 65, citrate 10, glucose 75 mmol/L
• Severe / unable to tolerate orally: IV fluids (Ringer's Lactate or Normal Saline)
• Avoid fruit juices, sodas (hyperosmolar, worsen diarrhoea)

2. Diet

• Early refeeding encouraged — BRAT diet (Bananas, Rice, Applesauce, Toast) or any easily digestible food
• Avoid lactose-containing foods temporarily

3. Symptomatic Agents

• Loperamide: First-line antimotility agent; reduces frequency; avoid in bloody diarrhoea or suspected invasive infection (risk of toxic megacolon)
• Bismuth subsalicylate: Mild antisecretory + antimicrobial effect
• Racecadotril: Enkephalinase inhibitor; antisecretory; safer than loperamide in children

4. Antibiotics

• NOT routinely indicated — most acute diarrhoea is viral and self-limiting
• Indicated when:

• Avoid antibiotics in EHEC (E. coli O157:H7) — increases risk of HUS

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3. CHRONIC DIARRHOEA (>4 WEEKS)

A. Pathophysiological Classification

1. Secretory Diarrhoea

• Mechanism: Active ion secretion or inhibition of ion absorption by enterotoxins, hormones, or laxatives → net intestinal fluid secretion
• Hallmarks:
  • Large volume (>1 L/day), watery
  • Persists with fasting (does NOT stop with fasting)
  • Osmotic gap <50 mOsm/kg (stool osmolality ≈ 2 × [Na + K])
• Causes:
  • Microscopic colitis (collagenous / lymphocytic colitis)
  • Bile acid malabsorption (post-cholecystectomy, ileal disease)
  • Peptide-secreting tumours: VIPoma (WDHA syndrome), Zollinger-Ellison, Carcinoid, Gastrinoma, Medullary thyroid carcinoma
  • Congenital chloride diarrhoea
  • Chronic laxative abuse (stimulant laxatives — senna, bisacodyl)
  • Addison's disease

2. Osmotic Diarrhoea

• Mechanism: Poorly absorbable solutes retain water in lumen → exceed colonic reabsorptive capacity
• Hallmarks:
  • Stops with fasting or when causative agent stopped
  • Osmotic gap >125 mOsm/kg
  • Stool pH <6 (carbohydrate fermentation)
• Causes:
  • Lactase deficiency (lactose intolerance)
  • Sorbitol, mannitol ingestion (sugar-free gum, diabetic foods)
  • Lactulose, Mg-containing antacids
  • Malabsorption syndromes (coeliac disease, SIBO, pancreatic exocrine insufficiency)
  • Osmotic laxative abuse (Mg sulphate, lactulose)

3. Inflammatory / Exudative Diarrhoea

• Mechanism: Mucosal inflammation, ulceration, exudation of blood, pus, proteins
• Hallmarks:
  • Bloody or mucoid stools
  • Fever, systemic symptoms
  • Faecal lactoferrin/calprotectin elevated
• Causes:
  • IBD: Crohn's disease, Ulcerative colitis
  • Infectious colitis: CMV, C. difficile, E. histolytica, Shigella, TB
  • Ischaemic colitis
  • Radiation enterocolitis
  • Colonic neoplasm
  • Diverticular disease

4. Malabsorptive Diarrhoea (Fat / Carbohydrate Malabsorption)

• Mechanism: Defective mucosal digestion or absorption → osmotic effect + fatty acid irritation of colon
• Hallmarks:
  • Steatorrhoea — pale, bulky, greasy, offensive, floating stools
  • Weight loss, nutritional deficiencies (fat-soluble vitamins A, D, E, K)
  • Sudan stain: fat globules in stool
• Causes:
  • Mucosal: Coeliac disease, tropical sprue, Whipple's disease, giardiasis, short bowel syndrome, intestinal lymphoma
  • Pancreatic: Chronic pancreatitis, cystic fibrosis, pancreatic cancer
  • Luminal: Bile acid deficiency (cholestatic liver disease, ileal resection), SIBO

5. Motility-Related Diarrhoea

• Mechanism: Rapid intestinal transit → reduced contact time for absorption
• Causes:
  • IBS-D (Irritable Bowel Syndrome — diarrhoea predominant)
  • Post-vagotomy, post-gastrectomy (dumping syndrome)
  • Hyperthyroidism
  • Diabetic autonomic neuropathy
  • Systemic sclerosis (scleroderma)

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B. Evaluation of Chronic Diarrhoea

Step 1 — History

Step 2 — Physical Examination

• Assess hydration, nutritional status, weight
• Abdominal mass, tenderness, distension
• Perianal disease (fistula, skin tags) → Crohn's
• Dermatitis herpetiformis → coeliac
• Skin pigmentation → Addison's / Whipple's
• Flushing → carcinoid
• Thyroid enlargement → hyperthyroidism
• Peripheral neuropathy / postural hypotension → diabetic autonomic neuropathy

Step 3 — Initial Investigations (All Patients)

Step 4 — Second-Line Investigations (Directed)

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C. Management of Chronic Diarrhoea

General

• Always treat the underlying cause — symptomatic treatment alone is insufficient
• Correct nutritional deficiencies (iron, B12, folate, vitamins A/D/E/K, zinc)
• Monitor weight and hydration

Disease-Specific

Symptomatic / Antidiarrhoeal Agents

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4. SPECIAL SITUATIONS

Traveller's Diarrhoea

• Most common in travel to Asia, Africa, Latin America
• Commonest cause: ETEC; also Campylobacter, Shigella, Salmonella, norovirus
• Self-limiting (3–5 days)
• Treatment: ORS + Loperamide + Azithromycin (if severe); Rifaximin for non-invasive (watery) traveller's diarrhoea

Diarrhoea in Immunocompromised / HIV

• Organisms not typically seen in immunocompetent hosts:
  • CD4 <200: Cryptosporidium, Microsporidium, Isospora (Cystoisospora) belli, MAC (Mycobacterium avium complex), CMV colitis
  • CD4 <50: Disseminated MAC, CMV enteritis
• Treatment: Antiretroviral therapy to restore immunity + organism-specific therapy

C. difficile Colitis

• Risk: Recent antibiotics (clindamycin, fluoroquinolones, cephalosporins, broad-spectrum PCN), hospitalisation, age >65, PPI use
• Diagnosis: Stool PCR for C. difficile toxin genes (most sensitive) or GDH + toxin EIA
• Treatment:
  • Mild–moderate: Oral Vancomycin 125 mg QID × 10 days or Fidaxomicin 200 mg BD × 10 days (lower recurrence rate)
  • Severe (WBC >15,000, Cr >1.5×baseline): Vancomycin (oral) + IV Metronidazole
  • Fulminant (ileus, megacolon, hypotension): Vancomycin (oral + per-rectal) + IV Metronidazole; surgical colectomy if refractory
  • Recurrent: Fidaxomicin > Vancomycin; Faecal microbiota transplant (FMT) for ≥3rd recurrence

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5. KEY DIFFERENTIATING POINTS AT A GLANCE

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6. ALARM FEATURES (ALWAYS INVESTIGATE)

• Rectal bleeding
• Nocturnal diarrhoea
• Weight loss >5 kg
• Fever
• Age >50 with new-onset change in bowel habit
• Family history of colorectal cancer or IBD
• Palpable abdominal or rectal mass
• Elevated CRP / calprotectin
• Anaemia or hypoalbuminaemia

Harrison's Chapter 47: Unintentional Weight Loss (UWL)

Clear summary with flowcharts and tables

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1) Definition and clinical significance

• Unintentional weight loss (UWL) = involuntary loss of weight, often insidious
• Clinically significant when:
  • >4.5 kg (10 lb) or
  • >5% body weight in 6 to 12 months
• Common in OPD and especially older adults
• Up to 25% may remain without a clear diagnosis after evaluation
• A substantial fraction has serious underlying disease (including malignancy)

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2) Major etiologic categories (high-yield)

• Medications (anorexia, nausea, dysgeusia)
• Social causes (poverty, isolation, inability to cook/feed)
• Dental/oral issues, dysphagia, malabsorption, chronic organ failure (cardiac/renal/hepatic/pulmonary)

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3) Pathophysiologic framework

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4) Red flags ("alarm features")

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5) History: focused diagnostic questions

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6) Physical examination checklist

• Vitals, BMI, temporal muscle wasting, sarcopenia
• Oral cavity and dentition
• Thyroid, lymph nodes
• Chest exam
• Abdominal mass/organomegaly
• Rectal exam (if indicated)
• Neurologic and cognitive screen
• Mood assessment

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7) Baseline investigations (first-line panel)

• CT chest/abdomen/pelvis
• Endoscopy/colonoscopy
• Malabsorption workup
• Autoimmune panel
• Bone marrow or biopsy (if hematologic concern)

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8) Evaluation algorithm (flowchart)

Patient with suspected UWL
        |
        v
Confirm true loss?
(>5% body weight in 6-12 months; serial measured weights)
        |
        +--> No -> Reassure, nutrition counseling, follow-up weight checks
        |
        v
Detailed history + exam
(localizing symptoms? psychiatric/social factors? medications?)
        |
        v
Baseline investigations
(CBC, ESR/CRP, CMP, TSH, glucose, UA, CXR ± age/risk-appropriate screening)
        |
        +--> Abnormal/localizing findings present
        |         |
        |         v
        |   Targeted diagnostics
        |   (CT/endoscopy/biopsy/infection/endocrine/rheumatology workup)
        |         |
        |         v
        |   Treat specific cause
        |
        +--> No clear cause after initial workup
                  |
                  v
Reassess for:
- Depression/dementia/substance use
- Medication adverse effects
- Social and functional barriers
- Occult malignancy risk
                  |
                  v
Nutritional intervention + close follow-up (1-3 months)
                  |
                  +--> Ongoing loss / new red flags -> expanded imaging and specialist referral
                  +--> Stabilization/improvement -> continue supportive management

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9) Differential diagnosis table by pattern

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10) Management principles

A. Treat the cause

• Malignancy, endocrine disease, infection, inflammatory disease, GI disorder, etc.

B. Nutritional rehabilitation

• Calorie and protein targets individualized
• Small frequent meals, oral nutrition supplements
• Micronutrient correction
• Dietitian involvement early

C. Address reversible contributors

• Deprescribe anorexigenic drugs when possible
• Treat pain, nausea, constipation, dysphagia
• Dental care, swallowing therapy if needed
• Treat depression/substance use
• Social support and meal access

D. Monitoring

• Serial weight (same scale/time), functional status, muscle mass trend
• Watch for frailty, falls, recurrent hospitalization

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11) Elderly-specific notes (very high yield)

• Causes are often multifactorial, not single-diagnosis
• Common hidden drivers: depression, cognitive decline, polypharmacy, social isolation, poor dentition
• UWL in older adults predicts morbidity, mortality, and functional decline
• Early multidisciplinary care improves outcomes

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12) Exam-ready ultra-short summary

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Approach to a Patient with Fever and Jaundice

Based on Harrison's Principles of Internal Medicine, 21st Ed. — Chapter 49

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1. DEFINITIONS

• Jaundice (Icterus): Yellow discolouration of skin, sclerae, and mucous membranes due to elevated serum bilirubin
  • Clinically visible when serum bilirubin >2.5–3 mg/dL
  • Normal serum bilirubin: 0.3–1.2 mg/dL
• Fever + Jaundice: A clinically important combination — always suggests a serious underlying condition (infection, sepsis, liver disease, haemolytic disorder)

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2. BILIRUBIN METABOLISM (Physiology Basis)

RBCs destroyed (85%) + ineffective erythropoiesis (15%)
                |
                v
        Haem → Biliverdin → UNCONJUGATED bilirubin
        (indirect, lipid-soluble, albumin-bound, NOT excreted in urine)
                |
                v
        Liver uptake (OATP1B1/3 transporters)
                |
                v
        UGT1A1 enzyme → CONJUGATED bilirubin
        (direct, water-soluble, excreted in bile)
                |
                v
        Bile → Intestine → Urobilinogen → Stercobilin (stool colour)
                                ↓
                        Reabsorbed → Urobilin (in urine)

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3. CLASSIFICATION OF JAUNDICE

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4. CAUSES OF FEVER WITH JAUNDICE

A. Infectious Causes (Leading Cause in Developing Countries)

B. Non-Infectious Causes

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5. HISTORY: KEY POINTS TO ELICIT

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6. PHYSICAL EXAMINATION: SYSTEMATIC APPROACH

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7. KEY CLINICAL SYNDROMES TO RECOGNISE

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8. INVESTIGATIONS: STEPWISE APPROACH

Step 1 — Initial Laboratory Panel

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Step 2 — Pattern Interpretation (LFT Pattern)

AST:ALT ratio >2:1 — strongly suggests alcoholic hepatitis ALT >1000 IU/L — think viral hepatitis, DILI, ischaemic hepatitis (shock liver)

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Step 3 — Imaging

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Step 4 — Specific Serological/Microbiological Tests

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9. DIAGNOSTIC ALGORITHM

FEVER + JAUNDICE
        |
        v
History + Physical Examination
        |
        v
LFTs: Bilirubin fractionation + AST/ALT/ALP/GGT + PT/INR + CBC
        |
        +---> Unconjugated bilirubin ↑ (direct <15%)
        |       |
        |       +--> Haemolytic: Peripheral smear, reticulocyte count,
        |            Coombs test, LDH, haptoglobin
        |            Malaria smear/RDT, G6PD screen
        |
        +---> Conjugated bilirubin ↑ + Hepatocellular pattern
        |     (AST/ALT very high, ALP mildly ↑)
        |       |
        |       +--> Viral serology (HAV, HBV, HCV, HEV, EBV, CMV)
        |            Drug/alcohol history
        |            Leptospirosis serology, malaria smear
        |            Autoimmune hepatitis panel
        |            USG abdomen
        |
        +---> Conjugated bilirubin ↑ + Cholestatic pattern
              (ALP/GGT very high, AST/ALT mildly ↑)
                |
                +--> USG abdomen: Bile duct dilated?
                        |
                        YES (Extrahepatic obstruction)         NO (Intrahepatic cholestasis)
                        MRCP / CT → stone/stricture/tumour     Drugs, PBC, PSC, sepsis,
                        ERCP if therapeutic needed             infiltrative disease
                                                                Liver biopsy if needed

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10. MANAGEMENT PRINCIPLES

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11. EXAM SUMMARY TABLE

Forced Alkaline Diuresis (Urinary Alkalinization)

Definition

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Principle (Ion Trapping)

• Weak acids (HA) become ionized (A⁻) in alkaline urine
• Ionized form is less reabsorbed in renal tubules
• Net effect: increased renal clearance of toxin

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Main Indications (high yield)

1. Salicylate poisoning (most important indication)
2. Phenobarbital poisoning (selected cases)
3. Occasionally with other weak acids where evidence supports use

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Standard Regimen (practical)

1. Correct volume depletion first (isotonic fluids)
2. Give IV sodium bicarbonate:
   • Common prep: 150 mEq NaHCO₃ in 1 L D5W
   • Infuse at rate to maintain urine alkalinity and good urine output
3. Targets:
   • Urine pH: 7.5 to 8
   • Serum pH: avoid severe alkalemia
   • Adequate urine output (around 1-2 mL/kg/h)
4. Potassium replacement is crucial
   • Hypokalemia prevents effective urinary alkalinization
5. Frequent monitoring:
   • ABG/VBG, serum electrolytes (K⁺, Na⁺, HCO₃⁻), creatinine
   • Urine pH hourly initially

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Role of Acetazolamide

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Complications

• Volume overload/pulmonary edema
• Metabolic alkalosis
• Hypokalemia
• Hypernatremia
• Hypocalcemia (rare symptomatic)
• Worsening in renal failure if not monitored

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Contraindications / Relative Contraindications

• Severe renal failure/anuria (ineffective)
• Pulmonary edema or uncompensated heart failure
• Significant alkalemia
• Severe hypokalemia not corrected
• Hemodynamic instability without resuscitation

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When to prefer Hemodialysis (especially in salicylate poisoning)

• Severe clinical toxicity (CNS symptoms, pulmonary edema, refractory acidosis)
• Renal failure
• Rising salicylate levels despite treatment
• Inability to alkalinize urine safely

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One-line exam answer