Below is an instruction that describes a task. Write a response that appropriately completes the request. ### Instruction: Need ideas from as many medical minds as possible please! Chronic respiratory failure - hypoxia. Worsening. Low BMI. Ruled out pulmonary and cardiac causes, whats in your differential?51F, 59, thin, white, USA. never-smoker, non-drinker; no prescriptions; unintended weight loss of now 28lbs since January, oxygen desats started in January w/ exertion, suddenly worsening in the past few days and now on continuous oxygen. Exhausted and weak. X-post for visibility. (This is for my mom)ETA see bottom of this, someone mentioned cervical spine issues, my mom has those, found in MRI in 2020!Ive posted about this a couple of times but need as many ideas as possible, and casting as wide a net as possible as weve hit a dead end and its looking bad.All pulmonary and cardiac testing done. Normal. (Only abnormal test so far has been an elevated 5-HIAA ordered bc hours-long intense hot facial flushing episodes began at the same time as the oxygen desats). Follow up with GI in 2 weeks.Over the past several days oxygen desats started coming on faster and going lower so after respiratory therapist consult now on continuous oxygen. Follow up with the pulmonary doc tomorrow but after 6 months of pulm/cardiac testing - and now sudden worsening of symptoms over the past few days - it seems like its time to look for other causes.What other specialist besides pulmonology or cardiology would you recommend? What would be in/on your differential list at this point?ETA: someone mentioned cervical spine issues causing this - here's her MRI of cervical spine and brain brief notes from neurologist about this from 2020:Her MRI of the C spine shows degenerative changes but most notable for disc protrusion at C6-C7 narrows the spinal canal to 5 mm. She is nearly asymptomatic at this point, but still encouraged her to discuss with neurosurgery for opinion given the findings.MRI of the brain shows multiple punctate foci, estimated at 30.. ### Response: I've been thinking about your mom since you posted last week about her worsening symptoms.The typical differential diagnosis for hypoxia is pretty simple to workup -- decreased partial pressure of oxygen (altitude), hypoventilation, decreased diffusion, VQ mismatch, and shunt). I would expect any reasonable pulmonologist could pretty easily work through that differential diagnosis, and I suspect if your mom got a shunt study that has gotten a thorough workup.There are some additional, rare causes of hypoxia/dyspnea that do exist. They are things that we predominantly see in the ICU, as they are typically acute causes. I categorize them as histocytotoxic and competitive. It's a bit complicated:Histocytotoxic causes do not exactly cause hypoxia. An example is cyanide. It uncouples the electron transport chain (ETC), which is the process of how cells utilize oxygen to make energy molecules). When the ETC is uncoupled/blocked you can not process oxygen, so physiologically it's like your body experiences extreme hypoxia. It's an immediately fatal process, so I can pretty much assure you your mom isn't dealing with cyanide toxicity. Perhaps you could bring up the idea of histocytoxic hypoxia to your mom's pulmonologist, though. She may have a chronic exposure to a substance that is causing hemoglobin dysfunction.Competetive hypoxia/hypoxemia is related to something that either outcompetes oxygen for hemoglobin binding or changes the hemoglobin conformation so that it no longer binds oxygen as well. There is something called methemoglobinemia (pronounced "met-hemoglobinemia", not meth-hemoglobinemia). It's also something we see on an acute setting in the hospital. There is a congenital/hereditary form, but it usually presents pretty immediately after birth. I wouldn't expect it to arise later in life like with your mother. There are plenty of acquired forms, but these usually happen acutely. It could also be worthwhile to bring up the idea of methemoglobin or other competitive forms of hypoxia/hypoxemia to your mom's pulmonologist.These are super rare and unlikely things, but it sure sounds like your mom doesn't have a common or simple problem. Hope this helps!.