A 54-year-old man with lifelong recurrent epistaxis, mucocutaneous telangiectasias on lips and tongue, and iron-deficiency anemia undergoes upper GI endoscopy. Multiple bright-red lesions are identified in the stomach and duodenum, as shown in the diagram. The structure marked **A** represents the characteristic mucosal finding. Which of the following best explains the pathophysiology of these lesions in this patient?

Explanation

## Why "Defective vascular morphogenesis with direct artery-to-vein shunts due to TGF-β/BMP9 signaling pathway mutations" is right The bright-red mucosal telangiectasias marked **A** are the hallmark of Hereditary Hemorrhagic Telangiectasia (HHT, Osler-Weber-Rendu syndrome). The pathophysiology is rooted in mutations affecting the TGF-β/BMP9 signaling pathway (ENG, ACVRL1, or SMAD4), which leads to defective vascular morphogenesis. This results in fragile, dilated post-capillary venules that lack intervening capillaries, creating direct artery-to-vein shunts. These abnormal vascular structures are inherently fragile and prone to bleeding, explaining the recurrent epistaxis and GI hemorrhage in this patient. The diagnosis is confirmed by the Curaçao criteria: recurrent epistaxis, mucocutaneous telangiectasias at characteristic sites (lips, tongue, fingertips), and visceral involvement (GI telangiectasia). ## Why each distractor is wrong - **Chronic portal hypertension leading to ectatic submucosal vessels and portal-systemic collaterals**: This describes esophageal varices and portal hypertensive gastropathy, not HHT. Portal hypertension causes different endoscopic findings and is not part of HHT pathophysiology unless there is concurrent hepatic cirrhosis (which is not mentioned here). - **Increased gastric acid secretion causing mucosal erosion and superficial vessel exposure**: This mechanism applies to peptic ulcer disease, not HHT. HHT telangiectasias are primary vascular malformations, not secondary to acid-induced erosion. - **Platelet dysfunction with impaired von Willebrand factor-mediated adhesion and bleeding tendency**: While HHT patients do bleed, the primary defect is not platelet function or von Willebrand factor. The bleeding is due to the inherent fragility of the telangiectatic vessels themselves, not a coagulation or platelet disorder. **High-Yield:** HHT = autosomal dominant vascular dysplasia with defective TGF-β/BMP9 signaling → fragile telangiectasias and AVMs; screen for pulmonary AVMs to prevent paradoxical stroke. [cite: International HHT Guidelines 2020; Curaçao Criteria]