High Altitude Pulmonary Edema - Mountain Sickness - HAPE

High Altitude Pulmonary Edema - - Mountain Sickness - HAPE

1. HIGH ALTITUDE PULMONARY EDEMA GUIDE : Dr. SACHIN HOSKATTI STUDENT : Dr. ZAHURA

2. Pulmonary edema defined as the abnormal accumulation of extravascular lung fluid Pathologic state that occurs when fluid is filtered into the lungs faster than it can be removed.

3. Two main pathophysiologic categories increased pressure edema increased permeability edema

4. Altitude physiology typically focuses on people above 2500 m; ~8000 ft.

5. Barometric pressure falls with increasing altitude, but composition of air remain same. According to Dalton’s law: Total Pressure of Air = Sum of Partial Pressure of All Gases. P= pO2+pCO2+pN2+pH2O

6. The French physiologist Paul Bert first recognized that the harmful effects of high altitude are caused by low oxygen tension.

7. Physiologically critical altitudes Upto 10,000 ft (3,000 m) ”safe zone of rapid ascent ” classically defines ‘high altitude’ At 18,000 ft (5,500 m) upper limit of permanent human inhabitation Above 20,000 ft (6,000 m) life is endangered without supplemental oxygen From 40,000 ft(12,000 m) Ozone layer starts

8. • • • • • Mount Everest 29,028 ft ( 8848mt ) Atmospheric Pr = 25 3 mmHg Inspired PO2=21%x(25 3 -47) =4 3 mmHg Unacclimatized person Unconscious in 45 seconds Dead in 4 to 6 minutes

9. PHYSIOLOGICAL RESPONSES TO HIGH ALTITUDE HYPOXIA: Accomodation Refers to immediate reflex adjustments of respiratory and cardiovascular system to hypoxia Acclimatization Refers to changes in body tissues in response to long term exposure to hypoxia

10. RESPONSES TO HYPOBARIC HYPOXIA Ventilatory Adaptations increase in ventilation decrease in alveolar CO2 in order to increase PAO2

11. Sensor- Carotid body- afferent activity ↑, PaO2 falls <60 mm Hg. can also be stimulated, at least transiently, by changes in carbon dioxide or hydrogen ion concentrations . The acclimatized person will continue to hyperventilate when returned to normoxia

12. Hypoxia master regulator of oxygen homeostasis that initiates transcription of over 100 hypoxia-inducible genes,

13. SLEEP AND PERIODIC BREATHING Recurrent central apneas will occur during sleep >2500 m increased alveolar ventilation ( hyperpnea ) from hypoxia hypocapnia competing with a normal elevation in the apneic (carbon dioxide) threshold with sleep

14. PULMONARY CIRCULATION At altitude the entire lung is hypoxic and CO2 levels are low as a consequence of hyperventilation Acute vasoconstriction over a few hours is a physiologic response With days to weeks of hypoxic exposure there occurs a structural remodeling of pulmonary arterioles and an increase in resting pulmonary arterial pressure and pulmonary vascular resistance

15. FLUID HOMEOSTASIS Extravasation may result from loss of tight channels due to oxidative stress and free radicals or a direct effect of hypoxia on ion channels. Local dysregulation of the renin–angiotensin–aldosterone system is proposed to play a role in this generalized response Lung edema, cerebral edema, and peripheral edema , dermal edema, edema of retinal vessels

16. ERYTHROPOIESIS AND HEMOGLOBIN AFFINITY Increase in EPO synthesis in response to HIF-1 and HIF-2 This acclimatization response takes a week or so and is reversible upon return to low altitudes.

17. Increased 2,3-DPG conc. in RBC : within hours, ↑ deoxy-Hb conc ---- locally ↑ pH --- ↑ 2,3-DPG --- ↓ oxygen affinity of Hb --- tissue O2 tension maintained at higher than normal level

18. Increased vascularity More capillaries open up in tissues than at sea-level This combined with systemic vasodilatation(also a hypoxic response) --- more O2 delivery to tissues.

19. Cellular level changes ↑ intracellular mitochondrial density ↑ conc. of cellular oxidative enzymes ↑ synthesis of Mb( O2-storing pigment) all aimed to improve O2 utilization.

20. CVS Cardiac output often increases as much as 30% immediately, then gradually return to normal in one to two weeks as the blood hematocrit increases

21. PHYSIOLOGICAL CHANGES

22. HIGH ALTITUDE RELATED MEDICAL DISORDERS

23. HIGH ALTITUDE HEADACHE ACUTE MOUNTAIN SICKNESS HIGH ALTITUDE PULMONARY EDEMA HIGH ALTITUDE CEREBRAL EDEMA CHRONIC MOUNTAIN SICKNESS

24. PATHOGENESIS

25. ACUTE MOUNTAIN SICKNESS AMS occurs after 4 to 36 hours of altitude exposure H eadache (usually frontal), nausea, vomiting, irritability, malaise, insomnia, and poor climbing performance . Symptoms frequently occur first or are more severe the morning after the first night at altitude.

26. Lake Louise Symptom Score Questionnaire self-administered tool to determine the severity of AMS S core of 4 and more is considered AMS S core of 10 and more is considered severe and requires immediate intervention.

27. Lake Louise Symptom Score Self-Report Questionnaire .

28. Risk factors Women may be less likely teenagers and young adults have a higher incidence history of migraine persistence of a patent foramen ovale Down syndrome congenital pulmonary abnormalities

29. HIGH ALTITUDE PULMONARY EDEMA Seen in ◦ 75-80% in persons doing heavy physical work in first 3-4 days ◦ Persons who acclimatized to high altitude, stay at sea levels for > 2wks& again rapidly re-ascend . Prevalence estimates are 0.5% to 2.0% of those rapidly ascending to altitude.

30. Contd … L ife-threatening form of non- cardiogenic pulmonary edema--- due to aggravation of hypoxia Not develop in gradual ascent & on avoidance of physical exertion during first 3-4 days of exposure.

31. Mechanism C aused by migration of fluid into extravasal space through endothelial damage along with shear stresses produced by increased cardiac output and pulmonary artery pressure. H ypoxic pulmonary artery vasoconstrictor response that is uneven throughout the lung

32. CLINICAL FEATURES Moderate symptoms of AMS may be present initially as the individual becomes more breathless Earliest indications are- ↓exercise tolerance , person feels fatigue, weakness & exertional dyspnoea . A cough develops, which is initially dry, then productive of frothy white sputum, later becoming blood tinged. C hest discomfort.

33. Contd … P ulse and respiratory rate are increased E levated jugular venous pressure Peripheral edema Auscultation of the chest reveals crackles at the bases . R ight ventricular heave and accentuated pulmonary component of the second heart sound

34. Preventive Medicine Preacclimatization in hypobaric chambers and normobaric hypoxic rooms reduces the risk of acquiring altitude illness on site, if it happens within a week before the trip.

35. Contd … K ey element is to limit the elevation change per day to less than 400 m/d S uggested rule is that above 3000 m (10,000 ft), ascent should be at a rate less than 300 m (1000 ft) per day, with a “rest” day (i.e., no additional ascent) every 3 days.

36. Contd … For direct travel to an altitude between 2500 m and 3000 m, stay at that altitude for two days and then ascend with a speed of 300 m per day “If symptoms of AMS develop, go no higher. If they become severe, go down .”

37. Contd … Individuals who ascend to high altitude should be advised to limit their activity for the first few days upon ascent . Adequate hydration should be encouraged

38. Contd … Prophylactic administration of acetazolamide is advisable for anyone with a prior history of AMS . Use of acetazolamide (250 mg at bedtime or 125 mg bid) for several days after arrival may improve sleep and ability to function during the day.

39. Contd … Corticosteroids (e.g., dexamethasone at a dose of 4 mg every 6 hours) is recommended as an alternative for individuals unable to take acetazolamide (e.g., those with sulfa allergy) The drug is continued for a few days at altitude.

40. Contd … In those who have experienced HAPE before, use of nifedipine prophylactically (slow-release formulation, 20 mg twice daily prior to ascent, then three times daily ) Mean systolic pulmonary artery pressure is lowered with this approach suggesting effects on smooth muscle relaxation. Prophylactic use of an inhaled ß-agonist may reduce the risk of HAPE

41. Treatment Descent is critical for survival . S trict rest and supplemental oxygen. Every 1% increase in oxygen concentration above 21% reduces the equivalent altitude by about 300 m . Anecdotally there are beneficial effects of a portable hyperbaric chamber --temporary measure while descent is arranged.

42. Contd … N ifedipine (10 mg sublingually) may be used. If clinically significant hypotension does not occur with the first dose of nifedipine , its administration can be repeated every 15 to 30 minutes. Phosphodiesterase inhibitors sildenafil and tadalafil are becoming fashionable drugs in the treatment of HAPE

43. GAMOW BAG Basically a sealed chamber with a pump(wt-6.3 kg). The person is placed inside the bag & it is fully inflated by pumping → effectively ↑ the conc. Of O2 molecules simulates a descent to lower altitude (In ~ 10 mins,it can create an "atmosphere" that corresponds to that at 3,000 - 5,000 ft lower)

44. Contd … After 1-2 hrs. in the bag, person's body chemistry will have "reset" to the lower altitude E nough time to walk them down to a lower altitude

45. A Gamow bag in action during equipment practice on the Apex 2 Expedition.

46. CHRONIC MOUNTAIN SICKNESS E xtreme polycythemia , with hemoglobin concentrations as high as 23 g/ dL and hematocrits as high as 83%. H eadache , dizziness, somnolence, fatigue, difficulty in concentration, and loss of mental acuity. Irritability , depression, and even hallucinations

47. Contd … Dyspnea on exertion is not common, but poor exercise tolerance Excessive erythrocytosis associated with a lower oxygen saturation and hypoxic ventilatory response with relative hypercapnia are the main features of CMS F ollowed by right ventricular enlargement, pulmonary hypertension, and remodeling of pulmonary arterioles.

48. TREATMENT Descent to sea level is the definitive treatment. F or those who wish to remain at altitude for family or economic reasons, phlebotomy and administration of supplemental oxygen are beneficial In the Andean ACE inhibition can effectively and safely ameliorate altitude polycythemia while also reducing proteinuria .

49. Contd … Medroxyprogesterone has been employed with some success; Although acetazolamide has been used in prevention of AMS, trials addressing its use in CMS are lacking. However , the drug may be useful in improving oxygen saturation during sleep and by this mechanism reducing hematocrit .

50. HIGH-ALTITUDE HEADACHE E xacerbated by insufficient hydration in the setting of increased water loss with hyperventilation, overexertion, and insufficient energy intake Vasodilation from hypocapnia may also contribute Acetaminophen or ibuprofen with hydration will improve this symptom

51. HIGH-ALTITUDE CEREBRAL EDEMA If the “mild” edema in the brain worsens toward compression of brain structure, the status of high-altitude cerebral edema (HACE) is reached. Signature symptoms are dizziness, severe almost unbearable headache, and vomiting. Ataxia is common , positive Romberg sign Somnolence, stupor, and changes in pupillary responsiveness mark the onset of a fatal stage. will progress to coma

52. TREATMENT Descent is critical. While awaiting evacuation, supplemental oxygen should be given. Several hours in a portable hyperbaric chamber may buy time Administration of dexamethasone (4–8 mg), intramuscularly in severe cases, or orally in less severe cases, helps reduce cerebral edema and should be given while awaiting evacuation; doses can be repeated every 6 hours

53. REFERENCES GANONGS REVIEW OF MEDICAL PHYSIOLOGY 24 TH EDITION FISHMANS TEXTBOOK OF PULMONARY DIAEASES 5 TH EDITION HARRISONS PRINCIPLES OF INTERNAL MEDICINE 20 TH EDITION