High-altitude renal syndrome

Everyone knows the famous George Mallory answer to the question about why he was climbing Mount Everest , “because it’s there.” But I just learned that he continued after that mic drop and spoke about doing science on these mountain climbing missions:

Sometimes science is the excuse for exploration. I think it is rarely the reason.

The three primary causes of high altitude sickness:

  1. Acute mountain sickness (AMS): headache, gastrointestinal symptoms (anorexia, nausea, vomiting), sleep disturbances, dizziness, fatigue
  2. High altitude pulmonary edema (HAPE)
  3. High altitude cerebral edema (HACE)

Lake Louise Acute Mountain Sickness severity score for acute mountain score:

Preventing AMS is usually dependent on limiting altitude gain, avoiding alcohol and drinking a lot of water.  Acetazolamide 125-250 bid is also effective.

The headache of acute mountain sickness can be decreased or avoided with medications:

Aspirin 320 mg po q4-hours x 3 doses, starting 1 to 2 hours prior to arrival

Ibuprofen 600 mg po q8-hours for at least 3 doses, starting 6 to 24 hours before ascent.

Ginko Biloba has been used with variable success as prophylaxis. 160-240 mg in divided doses

Dexamethasone 8 mg daily in divided doses can also be used for prophylaxis.

Nice review of AMS treatments and prophylaxis can be found here.

In studies looking at the etiology of AMS and HAPE, Vascular Endothelial Growth Factor and its soluble receptor sFlt-1 were thought to play a role. However in a study of 51 Denali mountaineers, blood levels were not associated with AMS.

The body has a number of strategies to adapt to high altitude trekking. Among the changes is the observation that the density of capillaries per unit of muscle rises. This sounds cool until you read that some scientists believe this is primarly due to a loss of muscle mass rather than growth in new capillaries.

Other strategies for adaptation include

  • Hyperpnea and tachypnea leading to hypocapnia
  • Hypoxia may trigger several receptors, including airway chemoreceptors
  • Tissue hypoxia also induces the production of hypoxia-inducible factor (HIF) transcription factors
  • Changes in metabolic pathways including oxidative metabolism, cell cycle and diminished myogenesis
  • Changes in hemoglobin oxygen affinity that alter arterial oxygen saturation and release to tissues
  • Increase in mitochondria and cytochrome oxidase occur but only after 7-9 days at altitude

Renal changes.

High-altitude renal syndrome is an asymptomatic chronic condition of high-altitude dwellers defined as:

  • High-altitude polycythemia
  • Systemic hypertension
  • Microalbuminuria
  • Hyperuricemia
  • Relatively preserved glomerular filtration rate

High altitude renal syndrome is part of the complex adaptive response to altitude.

Creatinine based GFR is unaffected by increases in altitude, however a study that used cystatin c based GFR assessment found a 3ml/min drop in GFR for every 1,000 meters the mountaineers ascended.

Interestingly, AMS was associated with higher eGFR.

Most electrolytes fall:

The decrease in serum bicarbonate comes from hypoxia induced respiratory alkalosis. Arterial pH at the top of Everest is estimated to be 7.7 to 7.8. PaO2 was 35 mmHg!

Trekkers in the mountains have hypovolemia due to increased insensible losses, increased anorexia, and decreased thirst. Additionally there is altitude induced diuresis. This diuresis seems to be an obligatory early phase of adaptation to altitude. The diuresis can cause a 1-3 liter loss of body water resulting in a 38% increase in blood viscosity at 5,800 meters.

The diuresis has variably been explained by suppression of ADH, increases in ANP and increases in BNP. Increases in BNP are associated with increased risk of AMS.

This paragraph is very interesting:

It remains unknown whether the altitude-induced decrease in plasma volume is adaptive or potentially harmful. If adaptive, then less effort should be made to correct ‘dehydration’, and fluid intake should be limited to simply following the thirst mechanism and to offsetting insensible losses (admittedly difficult to estimate, much less measure, on the mountain). Indeed, as discussed above, fluid retention rather than dehydration is associated with AMS. Perhaps diminished plasma volume is part of the body’s effort to supply oxygen to the most vital organs, overriding the not insubstantial risks of hyperviscosity and thrombosis associated with hemoconcentration.
There could be two beneficial effects of high-altitude diuresis:
  1. Early hemoconcentration elevates the blood concentration of hemoglobin prior to the slower onset of EPO-stimulated erythropoiesis
  2. Volume depletion reduces intravascular pressure and volume load on the lungs and brain, and may decrease renal oxygen consumption (90% of which reflects renal sodium reabsorption) due to diminished filtration

This article is excellent.