L2. High altitude pathophysiology

Question 1

What are the five main environmental challenges of high altitude?

Answer 1

Temperature, humidity, solar radiation, remoteness, and hypoxia

Question 2

What is ‘puna’ and who first described its types?

Answer 2

A term for high-altitude illnesses, described by Thomas Holmes Ravenhill

Question 3

What are the three types of ‘puna’ as described historically?

Answer 3

Normal (acute mountain sickness), nervous (cerebral edema), cardiac (pulmonary edema)

Question 4

What is the most common form of high-altitude illness?

Answer 4

Acute Mountain Sickness (AMS)

Question 5

At what altitude does Acute Mountain Sickness (AMS) typically occur?

Answer 5

Above 2500 meters

Question 6

What is the diagnostic criterion for AMS according to the Lake Louise Score?

Answer 6

Headache and a Lake Louise Score >3

Question 7

What physiological change is a key factor in AMS?

Answer 7

Increased cerebral blood flow

Question 8

What is the most important preventive measure for AMS?

Answer 8

Slow ascent

Question 9

What is the primary treatment for High Altitude Cerebral Edema (HACE)?

Answer 9

Descent

Question 10

What neurological symptoms are associated with HACE?

Answer 10

Confusion, ataxia, and depressed consciousness

Question 11

What causes pulmonary edema in High Altitude Pulmonary Edema (HAPE)?

Answer 11

Uneven hypoxic pulmonary vasoconstriction leading to high capillary pressure

Question 12

What physiological response is exaggerated in HAPE-susceptible individuals?

Answer 12

Increased hypoxic pulmonary vasoconstriction response

Question 13

What role does hypoxic pulmonary vasoconstriction (HPV) play in HAPE?

Answer 13

It causes uneven blood flow and high local capillary pressures

Question 14

How can iron supplementation impact high-altitude pulmonary hypertension?

Answer 14

It reduces pulmonary artery pressure by modulating the HIF pathway

Question 15

What is the main diagnostic marker for Chronic Mountain Sickness (CMS)?

Answer 15

Elevated haemoglobin levels

Question 16

What population shows a lower prevalence of CMS and why?

Answer 16

Tibetans, due to genetic adaptation to hypoxia

Question 17

What is the physiological impact of chronic high-altitude exposure on the pulmonary circulation?

Answer 17

Remodeling of pulmonary vessels leading to hypertension

Question 18

What genetic adaptation reduces pulmonary pressure in Tibetans?

Answer 18

Variants in the EPAS1 gene

Question 19

What treatment options are effective for CMS?

Answer 19

Venesection and acetazolamide

Question 20

What is the primary research challenge in studying high-altitude illnesses?

Answer 20

Logistical difficulties and replicating conditions in labs

Question 21

What experiments demonstrated the role of cerebral blood flow in AMS?

Answer 21

Increased cerebral blood flow correlates with AMS symptoms

Question 22

What is the key finding about pulmonary artery pressure in HAPE?

Answer 22

Elevated pulmonary artery pressure during hypoxia is a consistent finding

Question 23

How does hypoxia-induced pulmonary hypertension vary between individuals?

Answer 23

It varies greatly, predisposing some individuals to HAPE

Question 24

What evidence suggests capillary ‘stress failure’ as a mechanism for HAPE?

Answer 24

High capillary pressures can damage capillary walls, leading to edema

Question 25

What role does endothelin-1 play in high-altitude pulmonary hypertension?

Answer 25

It is elevated in HAPE and contributes to vascular constriction

Question 26

What did the iron infusion experiments reveal about pulmonary pressure?

Answer 26

Iron infusion rapidly reduced pulmonary pressure, implicating HIF pathway

Question 27

What imaging evidence supports brain swelling in HACE?

Answer 27

Brain swelling and increased intracranial pressure were observed

Question 28

What was observed in MRI scans of HACE patients after recovery?

Answer 28

Resolution of swelling and microbleeds was seen

Question 29

What were the findings of the bronchoscopy experiments in HAPE patients?

Answer 29

Increased albumin in bronchoalveolar lavage fluid indicated capillary leakage

Question 30

What genetic evidence supports the blunted HPV response in Tibetans?

Answer 30

EPAS1 mutations reduce HPV, aiding adaptation

Question 31

What role does the EPAS1 gene mutation play in high-altitude adaptation?

Answer 31

Associated with lower haemoglobin levels and blunted HPV in Tibetans

Question 32

What differences in ventilatory response were observed in chronic mountain sickness?

Answer 32

Lower ventilatory responses correlated with higher CMS prevalence

Question 33

What experimental model demonstrated the protective role of iron against HPV?

Answer 33

Iron supplementation prevented exaggerated HPV

Question 34

What were the findings about pulmonary remodelling in long-term high-altitude residents?

Answer 34

Chronic hypoxia causes vascular thickening and hypertension

Question 35

What challenges are associated with studying high-altitude physiology in remote settings?

Answer 35

Remoteness, harsh environment, and logistical difficulties

Question 36

What was the purpose of the 'Pike's Peak Expedition' in high-altitude research?

Answer 36

Studied acclimatization and physiological responses

Question 37

What conclusions were drawn from salmeterol studies on HAPE susceptibility?

Answer 37

Salmeterol reduced HAPE risk by enhancing fluid clearance

Question 38

What did the case studies of Indian soldiers reveal about high-altitude illnesses?

Answer 38

Showed progression from AMS to HACE with elevated pressures

Question 39

What are the logistical advantages of conducting high-altitude experiments in South America?

Answer 39

South America offers accessible altitudes with better infrastructure

Question 40

What did field studies at Cerro de Pasco reveal about high-altitude pulmonary pressure?

Answer 40

Revealed rapid changes in pulmonary pressure with altitude