Science of High Altitude Pulmonary Edema.

 

Science of High Altitude Pulmonary Edema

PKGhatak, MD

Airlines are carrying a large number of people to high altitude sky resorts and mountain climbing facilities. These popular recreational activities also put people at risk of mountain sickness and acute pulmonary edema.

At sea level, the partial pressure of oxygen (Pio2) in the air is 160 mm Hg. At 8,000 ft the Pio2 is 120 mmHg, at 11,000 ft. above sea level the Pio2 is 87 mmHg, and at extreme high altitude, 18000 ft., the Pio2 is only 50 mm Hg.

At any altitude above 4,000 ft. the blood level of oxygen is low and becomes lower at higher and higher altitudes.

Air enters the alveoli of the lungs with inhalation. On the way to the alveoli, the air becomes fully saturated with water vapor. At a body temperature of 98.8 degrees F, the partial pressure of H2O is 47 mmHg, PiO2 is diluted as air enters the alveoli and Pi02 becomes (160-47) 113 mmHg. The blood in the capillary is separated from the alveolar air by only one layer of cells. The oxygen(O2) of air first gets dissolved in the alveolar fluid and then rapidly binds with hemoglobin of blood because of the high affinity of oxygen to hemoglobin and forms loose compound oxyhemoglobin. The mixed venous blood Pvo2 is 40mmHg, favoring oxygen flow toward the blood due to a pressure gradient of 83 mmHg (113- 40).

When this is happening carbon dioxide (CO2) of blood is moving in the opposite direction – from blood into the alveoli, again due to the pressure gradient of 40 mmHg of blood to the + 0 mmHg of alveolar air. The CO2 binding is accelerated by the presence of enzymes- carbonic acid anhydrase. As little as 2 to 10 mmHg pressure gradient CO2 can move rapidly and completely.

As the blood leaves the alveoli and returns to the left side of the heart, the O2 carrying capacity of blood is at maximum – the PaO2(partial pressure of arterial blood) is over 90 mmHg and the O2 saturation (O2 sat) is 98 to 100 %.

Let's look at what happens at 8,000 ft. The Pio2 in the alveoli is 73 mmHg (120 – 47). The O2 gradient is (73-40) 43 mmHg. At 43 mmHg, the O2 sat is 75 %. This is significant Hypoxemia and patients immediately develop symptoms.

Effects of Hypoxia on Local Population.

The people living in the high plateau of Tibet for over 35000 years. The average altitude of the Tibetan plateau is 11,000 ft. They have developed an advanced adaptive mechanism, and it stands in contrast to the rest of high altitude residents of Ethiopia and Andes Mountain people. In Peru and Bolivia, the present population moved in about 1,100 to 800 years ago and has yet to adopt the full high altitude mechanisms of the Tibetan population.

In Peruvians and Bolivians, the hemoglobin level is higher due to the increased Erythropoietin activity, the minute ventilation is decreased, pulmonary arterial pressure is higher, right ventricular hypertrophy is present, Nitric Oxide(NO) levels are lower compared with Tibetan. They have more complications during pregnancy and childbirth, and newborns have lower weight at birth.

In Tibetan the mutation of EGLN1 and EPAS1 genes carry the adaptive oxygen sensing and high altitude hypoxic adaptive mechanisms. The hypoxic stimuli of carotid and aortic bodies are muted. There is no hyperventilation. At 85 mmHg, the O2 saturation of the air is over 87%, the nitrogen oxide levels in the lungs and blood are high. The hemoglobin levels are not elevated. The resting ventilation is high, and lung volumes are larger. The smooth muscles of the pulmonary artery are not hypertrophic, pulmonary hypertension does not happen. The weight of newborns is normal.

Effect of Hypoxia on Recent Arrivals.

Acute Mountain Sickness.

On the very day of arrival, symptoms of cerebral anoxia develop. The main symptoms are headaches, dizziness, nausea, anorexia, fatigue and shortness of breath on minimal activities, difficulty sleeping and mild dry cough. Swelling of face, hands and feet develop.

High Altitude Pulmonary Edema (HAPE).

From day 2 to day 4 of arrival, the symptoms are more severe. The shortness of breath at rest develops. The temperature rises to 101F degrees. Palpitation and rapid breathing, mental confusion, incoordination and prostration soon appear. The cough becomes productive of pink frothy sputum and occasionally becomes bloody, labored breathing with gurgling sounds on breathing is heard, cyanosis, and slow heart rate and BP began to fall. Acute respiratory distress and Acute Pulmonary edema set in.

High Altitude Cerebral Edema (HACE).

Anoxia of the brain cells is responsible for increased fluid accumulation in between brain cells and produces persistent headache, dizziness, nausea, the sensation of pins and needles, lethargy, incoordination, loss of sleep, tinnitus, violent behavior and loss of consciousness and seizures.

Pathophysiology of HAPE.

1. Hypoxia producing capillary leaks.

The tight junctions between the type I alveolar cells prevent excess fluid accumulation in the alveolar space. A thin layer of fluid is essential for the normal function of ventilation and gas exchanges. The integrity of the alveolar membrane depends on oxygen; in the hypoxic condition, the alveolar type I cells develop gaps between cell junctions and fluid escape in the alveolar space. Nitric oxide production is reduced, lack of nitric oxide in the lung results in smooth muscle contraction of pulmonary arteries and Pulmonary arterial BP (PBP) is elevated. That produces Right heart strain and hypertrophy. Dr. J.B. Web described the genesis of the capillary leak “The hydrostatic stress that exceeds the load bearing limits of the collagen network [of alveoli] results in rupture of the basement membrane.”

2. Derailed removal of fluid.

Two separate but interrelated paths are present in the lung to ensure fluid removal- these are

A. Starling force driven sodium channels.

B. Na and K iron ATPase dependent trans-epithelial sodium channels.

The functioning of both these channels is defective in hypoxic conditions.

If the foramen ovale was not completely closed the opening of the foramen ovale enlarges and the Right to Left shunt takes place which makes hypoxia more profound and early right heart failure develops. Endothelin1 activities are reduced and contribute to Pulmonary BP elevation.

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 C. Increase in pro-inflammatory markers in the lung.

Analysis of bronchial fluid obtained during the Intubation of HAPE patients show an increase in pro-inflammatory markers namely interleukin IL-1 beta, IL6, IL8, TNF alpha. In addition, the total cell counts are elevated, and increased lung macrophages are present. Blood levels of LDH, CRP, and total proteins are increased. The monocytes attractive protein1alpha (MIPA1alpha) and monocytes chemo-attractant protein1 and IL8 are significantly higher in Chronic Mountain sickness.

D. The anti-inflammatory markers- IL alpha, IL-10, show no change or levels are decreased.

Chronic Mountain Sickness.

Prolonged stay at high altitude results in the continuation of acute symptoms, in addition, the patients develop sleep disorders. Mental confusion, abnormal behavior, cognitive impairment and various neurological symptoms.

Returnee of Native of High Altitude.

High altitude people living on a lower plane for an extended period and then on returning to high altitude experience a more severe form of acute Pulmonary edema. The basic reason for this disease is not known.

Diagnosis of HAPE.

Respiratory symptoms in recent arrivals at high altitudes should always alert the possibility of acute mountain sickness or HAPE. This is the primary diagnosis and other possibilities like cardiac failure, PE, and pneumonia should come later.

Shortness of breath at minimal effort, or at rest, temperate elevation, frothy pink sputum, air hunger, cyanosis, tachycardia, and increased rate of respiration are universally present. Moist sounds, rales, on auscultation on both sides, chest x-rays- bilateral mid-zone, bat wing shaped infiltrates, and a low O2 saturation by pulse oximetry should be diagnostic of HAPE.

 

Immediate oxygen is administered by any available source to keep the O2 sat over 90%. Portable Hyperbaric oxygen chambers are generally available or should be made available as soon as possible. An arrangement must be made to take the patients to a lower altitude to a better medical facility.

Medications.

Nifedipine 20 mg tablets are given at 4 hourly to lower Pulmonary hypertension (PAP). Acetazolamide, a diuretic, also lowers PAP by blocking calcium channels, Tadalafil, a phosphodiesterase inhibitor, is also used. A bronchodilator Salmeterol is used to ease breathing.

Dexamethasone is used when cerebral edema is suspected in HAPE with predominate cerebral symptoms.

Prevention of acute mountain sickness and HEPA.

People should consult mountaineering school/ training centers at the time of preparation for such events. The day before arrival Nifedipine 80 mg long acting tablets one tablet and on arrival day and onwards one tablet should be taken. No physical activities on the 1^st day. Sleeping at a lower altitude should be considered. Daily hiking/climbing should be limited to 1500 feet.

Use portable oxygen when the pulse oximeter shows saturation below 90 %. And seek advice from the team leader or the guide.

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