L2. High altitude pathophysiology Flashcards
What are the five main environmental challenges of high altitude?
Temperature, humidity, solar radiation, remoteness, and hypoxia
What is ‘puna’ and who first described its types?
A term for high-altitude illnesses, described by Thomas Holmes Ravenhill
What are the three types of ‘puna’ as described historically?
Normal (acute mountain sickness), nervous (cerebral edema), cardiac (pulmonary edema)
What is the most common form of high-altitude illness?
Acute Mountain Sickness (AMS)
At what altitude does Acute Mountain Sickness (AMS) typically occur?
Above 2500 meters
What is the diagnostic criterion for AMS according to the Lake Louise Score?
Headache and a Lake Louise Score >3
What physiological change is a key factor in AMS?
Increased cerebral blood flow
What is the most important preventive measure for AMS?
Slow ascent
What is the primary treatment for High Altitude Cerebral Edema (HACE)?
Descent
What neurological symptoms are associated with HACE?
Confusion, ataxia, and depressed consciousness
What causes pulmonary edema in High Altitude Pulmonary Edema (HAPE)?
Uneven hypoxic pulmonary vasoconstriction leading to high capillary pressure
What physiological response is exaggerated in HAPE-susceptible individuals?
Increased hypoxic pulmonary vasoconstriction response
What role does hypoxic pulmonary vasoconstriction (HPV) play in HAPE?
It causes uneven blood flow and high local capillary pressures
How can iron supplementation impact high-altitude pulmonary hypertension?
It reduces pulmonary artery pressure by modulating the HIF pathway
What is the main diagnostic marker for Chronic Mountain Sickness (CMS)?
Elevated haemoglobin levels
What population shows a lower prevalence of CMS and why?
Tibetans, due to genetic adaptation to hypoxia
What is the physiological impact of chronic high-altitude exposure on the pulmonary circulation?
Remodeling of pulmonary vessels leading to hypertension
What genetic adaptation reduces pulmonary pressure in Tibetans?
Variants in the EPAS1 gene
What treatment options are effective for CMS?
Venesection and acetazolamide
What is the primary research challenge in studying high-altitude illnesses?
Logistical difficulties and replicating conditions in labs
What experiments demonstrated the role of cerebral blood flow in AMS?
Increased cerebral blood flow correlates with AMS symptoms
What is the key finding about pulmonary artery pressure in HAPE?
Elevated pulmonary artery pressure during hypoxia is a consistent finding
How does hypoxia-induced pulmonary hypertension vary between individuals?
It varies greatly, predisposing some individuals to HAPE
What evidence suggests capillary ‘stress failure’ as a mechanism for HAPE?
High capillary pressures can damage capillary walls, leading to edema
What role does endothelin-1 play in high-altitude pulmonary hypertension?
It is elevated in HAPE and contributes to vascular constriction
What did the iron infusion experiments reveal about pulmonary pressure?
Iron infusion rapidly reduced pulmonary pressure, implicating HIF pathway
What imaging evidence supports brain swelling in HACE?
Brain swelling and increased intracranial pressure were observed
What was observed in MRI scans of HACE patients after recovery?
Resolution of swelling and microbleeds was seen
What were the findings of the bronchoscopy experiments in HAPE patients?
Increased albumin in bronchoalveolar lavage fluid indicated capillary leakage
What genetic evidence supports the blunted HPV response in Tibetans?
EPAS1 mutations reduce HPV, aiding adaptation
What role does the EPAS1 gene mutation play in high-altitude adaptation?
Associated with lower haemoglobin levels and blunted HPV in Tibetans
What differences in ventilatory response were observed in chronic mountain sickness?
Lower ventilatory responses correlated with higher CMS prevalence
What experimental model demonstrated the protective role of iron against HPV?
Iron supplementation prevented exaggerated HPV
What were the findings about pulmonary remodelling in long-term high-altitude residents?
Chronic hypoxia causes vascular thickening and hypertension
What challenges are associated with studying high-altitude physiology in remote settings?
Remoteness, harsh environment, and logistical difficulties
What was the purpose of the ‘Pike’s Peak Expedition’ in high-altitude research?
Studied acclimatization and physiological responses
What conclusions were drawn from salmeterol studies on HAPE susceptibility?
Salmeterol reduced HAPE risk by enhancing fluid clearance
What did the case studies of Indian soldiers reveal about high-altitude illnesses?
Showed progression from AMS to HACE with elevated pressures
What are the logistical advantages of conducting high-altitude experiments in South America?
South America offers accessible altitudes with better infrastructure
What did field studies at Cerro de Pasco reveal about high-altitude pulmonary pressure?
Revealed rapid changes in pulmonary pressure with altitude
