In a 30-year-old male with IgA nephropathy and three weeks of gastrointestinal bleeding resulting in a hemoglobin of 5 g/dL, what is the most likely cause of his severe dyspnoea?

Severe Anemia from Gastrointestinal Bleeding

The severe dyspnoea in this patient is caused by profound anemia (hemoglobin 5 g/dL) resulting in inadequate oxygen delivery to tissues, compounded by his underlying chronic kidney disease from IgA nephropathy. 1

Primary Mechanism of Dyspnoea

Anemia is a well-established non-cardiac cause of dyspnoea, as explicitly listed in the European Society of Cardiology guidelines for heart failure evaluation. 1 When hemoglobin drops to 5 g/dL—less than half the normal value—the blood's oxygen-carrying capacity is critically reduced, forcing compensatory mechanisms:

• Increased cardiac output to maintain tissue oxygen delivery, leading to tachycardia and increased work of breathing 1
• Tachypnoea (respiratory rate >20/min) as a compensatory response to tissue hypoxia 1
• Dyspnoea, fatigue, chest pain, and palpitations are cardinal symptoms of hemodynamic compromise from acute blood loss 1

Clinical Context Supporting This Diagnosis

The timeline and presentation strongly support anemia as the cause:

• Three weeks of gastrointestinal bleeding provides sufficient duration for progressive anemia to develop 1
• Hemoglobin of 5 g/dL represents severe anemia requiring urgent transfusion 1
• IgA nephropathy predisposes to anemia through multiple mechanisms: chronic kidney disease reduces erythropoietin production, and low hemoglobin independently predicts IgAN progression 2, 3

Excluding Alternative Causes

While evaluating acute dyspnoea, other causes must be considered but are less likely here:

• Pulmonary embolism: Although nephrotic syndrome (which can occur in IgAN) increases thromboembolism risk, the question does not indicate nephrotic-range proteinuria or hypoalbuminemia 1
• Volume overload/heart failure: Possible with advanced CKD, but the prominent feature is ongoing bleeding with severe anemia rather than fluid retention 1
• Pneumonia or infection: Not suggested by the clinical scenario 1

Immediate Management Priorities

Aggressive resuscitation and blood transfusion are the first priorities before attempting to identify the bleeding source:

• Blood transfusion is determined by hemodynamic status, rate of bleeding, age, and comorbidities (coronary disease, COPD, cirrhosis) 1
• Orthostatic hypotension, pallor, tachycardia, and dyspnoea indicate hemodynamic compromise requiring urgent intervention 1
• Correction of coagulopathy if INR >1.5 or platelets <50,000/µL with fresh frozen plasma or platelet transfusion 1

Diagnostic Approach to Bleeding Source

Once hemodynamically stable, source identification is essential:

• Upper endoscopy (EGD) is first-line for suspected upper GI bleeding, which can present as rectal bleeding (hematochezia) in brisk bleeding 1, 4
• Nasogastric aspirate may be negative in 3-16% of confirmed upper GI bleeding cases 1, 4
• Digital rectal examination helps exclude anorectal pathology and confirms stool appearance 1
• Colonoscopy if lower GI source suspected, though 75% of lower GI bleeding stops spontaneously 1

IgA Nephropathy-Specific Considerations

The underlying kidney disease adds complexity:

• Anemia develops early in CKD (>40% of CKD patients are anemic) due to inadequate erythropoietin production 2
• Low hemoglobin independently predicts IgAN progression with increased risk of kidney failure (HR 1.91 for lowest vs highest quartile) 3
• Renal function assessment should include creatinine, BUN, and electrolytes to evaluate CKD contribution 1