Correct Answer: D. Protein-losing enteropathy
The clinical presentation of pink frothy sputum with hemosiderin-laden macrophages at autopsy is pathognomonic for chronic pulmonary edema secondary to elevated pulmonary venous pressure. Hemosiderin-laden macrophages (also called "heart failure cells") form when chronic pulmonary congestion causes repeated alveolar hemorrhage; red blood cells are phagocytosed by alveolar macrophages, and hemoglobin is metabolized to hemosiderin, which stains blue with Prussian blue stain. This finding is seen in any condition causing chronically elevated pulmonary venous pressure. Protein-losing enteropathy is a gastrointestinal condition characterized by excessive protein loss through the intestinal mucosa (seen in conditions like celiac disease, Crohn's disease, or lymphatic obstruction). It causes hypoproteinemia and edema but does NOT cause pulmonary venous congestion or pulmonary edema. Therefore, hemosiderin-laden macrophages would NOT be present in protein-losing enteropathy. The other three options all lead to elevated pulmonary venous pressure: right heart failure causes backup of blood into the lungs, pulmonary vein obstruction directly impedes venous drainage, and volume overload increases pulmonary blood volume—all resulting in chronic pulmonary congestion and the characteristic histological finding.
Why the other options are wrong
A. Right heart failure — Right heart failure causes backup of blood into the pulmonary circulation, leading to chronically elevated pulmonary venous pressure. This results in repeated alveolar hemorrhage and formation of hemosiderin-laden macrophages. This is a classic cause of the autopsy finding described, making it WRONG as the answer to 'in which condition is this NOT seen.' B. Pulmonary vein obstruction — Pulmonary vein obstruction (from thrombosis, stenosis, or extrinsic compression) directly impedes venous drainage from the lungs, causing sustained elevation of pulmonary capillary pressure. This leads to chronic pulmonary edema and hemosiderin-laden macrophages. It is a well-recognized cause of the autopsy finding, making it WRONG as the answer. C. Volume overload — Volume overload (from excessive fluid administration, renal failure, or cirrhosis) increases pulmonary blood volume and pulmonary venous pressure. Chronic volume overload causes pulmonary congestion, alveolar hemorrhage, and hemosiderin-laden macrophages. This is a common cause of the described pathology, making it WRONG as the answer to the question.
High-Yield Facts
- Hemosiderin-laden macrophages (heart failure cells) are pathognomonic for chronic pulmonary venous congestion and indicate repeated alveolar hemorrhage.
- Pink frothy sputum in acute decompensation indicates pulmonary edema with hemorrhage; hemosiderin deposition occurs with chronic congestion.
- Protein-losing enteropathy causes hypoproteinemia and peripheral edema but does NOT cause pulmonary venous congestion.
- Elevated pulmonary venous pressure is the common mechanism in RV failure, pulmonary vein obstruction, and volume overload—all cause hemosiderin deposition.
- Prussian blue stain is used to demonstrate hemosiderin in alveolar macrophages on histology; this is diagnostic of chronic pulmonary congestion.
Mnemonics
HFC (Heart Failure Cells) Hemosiderin-laden macrophages = From chronic Congestion. Remember: these cells appear when the lungs are chronically 'congested' with blood, not when protein is lost from the gut. PELVIC causes of hemosiderin deposition Pulmonary vein obstruction, Elevated venous pressure (RV failure), Left heart failure, Volume overload, Increased capillary pressure, Chronic congestion. Protein-losing enteropathy is NOT in this list.
NBE Trap
NBE pairs the dramatic clinical presentation (pink frothy sputum + autopsy finding) with a gastrointestinal diagnosis to test whether students understand that hemosiderin deposition requires pulmonary venous congestion, not systemic protein loss. Students who confuse edema mechanisms (thinking all causes of edema lead to pulmonary findings) may incorrectly eliminate protein-losing enteropathy.
Clinical Pearl
In Indian clinical practice, hemosiderin-laden macrophages are a key autopsy finding in chronic heart failure and rheumatic mitral stenosis (common in India). Protein-losing enteropathy, seen in conditions like tropical sprue or celiac disease, presents with diarrhea and malnutrition—not pulmonary edema—making it the clear outlier in this question.
_Reference: Robbins Ch. 4 (Hemodynamic Disorders); Harrison Ch. 246 (Pulmonary Edema)_