Pathophysiology
Clinical meaning
Palliative symptom assessment addresses the multidimensional suffering that arises as organ systems progressively fail in advanced illness. Pain in palliative patients often involves mixed nociceptive and neuropathic mechanisms: tumor invasion of bone activates periosteal nociceptors and triggers osteoclast-mediated bone resorption via RANKL signaling, while nerve compression or infiltration causes Wallerian degeneration with ectopic firing and central sensitization. The concept of total pain (Cicely Saunders) recognizes that physical pain is amplified by psychological distress (fear, depression), social suffering (isolation, financial burden), and spiritual anguish (loss of meaning). Dyspnea in advanced disease results from multiple converging mechanisms: reduced lung compliance from effusions or lymphangitic carcinomatosis, respiratory muscle weakness from cachexia and diaphragmatic fatigue, anemia reducing oxygen-carrying capacity, and anxiety activating the sympathetic nervous system. Low-dose opioids reduce dyspnea perception by decreasing the medullary respiratory center's sensitivity to rising PaCO2 without causing clinically significant respiratory depression at palliative doses. Cancer cachexia is driven by pro-inflammatory cytokines (TNF-alpha, IL-6, IL-1) that activate ubiquitin-proteasome proteolysis in skeletal muscle and suppress appetite via hypothalamic signaling โ this is distinct from starvation and does not reverse with...