Altitude Sickness

Risk Factors

Rapid ascent rate (>500 m/day above 2,500 m), prior history of altitude illness, permanent residence at low elevation, young adults (tend to ascend aggressively), obesity, pre-existing cardiopulmonary disease, individual genetic susceptibility (blunted hypoxic ventilatory response)

Etiology

Hypobaric hypoxia caused by decreased barometric pressure at high altitude, leading to reduced partial pressure of inspired oxygen ( $P_{i}O_2$ )

Presentation

Headache (cardinal symptom), nausea, fatigue, dizziness, and sleep disturbance developing within 6 to 12 hours of ascent above 2,500 m. Severe forms present with dyspnea at rest, cough with pink frothy sputum (pulmonary edema), or ataxia and confusion (cerebral edema)

Classic Exam

Mild form: unremarkable exam. Pulmonary form: bilateral crackles, central cyanosis, tachypnea, tachycardia. Cerebral form: truncal ataxia, papilledema, altered level of consciousness

Diagnostics

Clinical diagnosis using the Lake Louise Score. Decreased $S p O_{2}$ disproportionate to altitude. Chest radiograph shows bilateral patchy infiltrates in pulmonary edema. Brain MRI shows white matter edema (especially the splenium of the corpus callosum) in cerebral edema

Management

Descent is always the definitive treatment. Acetazolamide for the mild form. Nifedipine and supplemental $O_{2}$ for pulmonary edema. Dexamethasone and supplemental $O_{2}$ for cerebral edema. Portable hyperbaric chamber (Gamow bag) when descent is not possible

Keywords

"Recently hiked to high altitude," "headache worse at night/upon waking," "rapid ascent over two days," "pink frothy sputum at altitude," "ataxia after climbing," "nonproductive cough at basecamp"

01Pathophysiology

At sea level, barometric pressure is approximately 760 mmHg, maintaining an alveolar oxygen tension ( $P_{A} O_{2}$ ) sufficient for normal gas exchange. As altitude increases, barometric pressure falls proportionally, and with it the $P_{i}O_2$ . At 2,500 m (8,200 ft), the $P_{i}O_2$ drops to roughly 110 mmHg (compared to ~150 mmHg at sea level). At 5,500 m, it falls to approximately 75 mmHg. This reduction in driving pressure for oxygen is the fundamental trigger for all forms of altitude illness.

The body's immediate compensatory response is increased minute ventilation driven by peripheral chemoreceptors (carotid bodies sensing low $P a O_{2}$ ). This hypoxic ventilatory response (HVR) blows off $C O_{2}$ , producing a respiratory alkalosis. The kidneys then compensate over 24 to 48 hours by excreting bicarbonate in the urine, slowly correcting blood pH toward normal. This process, called acclimatization, is the reason gradual ascent is protective. Individuals with a blunted HVR acclimatize poorly and are at higher risk.

Acute Mountain Sickness (AMS) is thought to result from mild, subclinical cerebral edema. Hypoxia causes cerebral arteriolar vasodilation, increasing cerebral blood flow. Combined with impaired cerebral autoregulation and increased capillary permeability due to hypoxia-induced endothelial dysfunction, interstitial fluid accumulates in the brain parenchyma. This explains the headache (from meningeal stretch and trigeminovascular activation), the nausea (from raised intracranial pressure), and the sleep disturbance (from periodic breathing due to oscillating chemoreceptor drive at altitude).

High-Altitude Pulmonary Edema (HAPE) is a form of non-cardiogenic pulmonary edema. The mechanism begins with exaggerated, uneven hypoxic pulmonary vasoconstriction (HPV). Because HPV is patchy, some capillary beds are overperfused at very high pressures while others are constricted. The overperfused segments experience stress failure of pulmonary capillaries, allowing protein-rich, hemorrhagic fluid to leak into the alveolar spaces. This is why the sputum is characteristically pink and frothy. Importantly, left atrial and wedge pressures are normal, because this is not heart failure. The pulmonary artery pressure, however, is markedly elevated.

High-Altitude Cerebral Edema (HACE) represents the severe end of the AMS spectrum. Ongoing hypoxia causes progressive breakdown of the blood-brain barrier, leading to vasogenic edema, particularly in the white matter of the corpus callosum. This explains the hallmark findings of truncal ataxia (from posterior fossa edema) and altered mental status. HACE can progress rapidly to coma and death if not treated with immediate descent.

02Classification and Clinical Manifestation

Altitude illness exists on a clinical spectrum. The three recognized syndromes and their hallmark features are:

Acute Mountain Sickness (AMS)

Typical Onset: 6 to 12 hours after arrival
Altitude Threshold: Above 2,500 m (8,200 ft)
Cardinal Features: Headache (required) plus nausea, vomiting, fatigue, dizziness, or sleep disturbance
Severity: Mild to moderate; self-limiting with rest

High-Altitude Pulmonary Edema (HAPE)

Typical Onset: 2 to 4 days after arrival
Altitude Threshold: Usually above 3,000 m (10,000 ft)
Cardinal Features: Dyspnea at rest, dry cough progressing to productive cough with pink frothy sputum, exercise intolerance, cyanosis
Severity: Severe; leading cause of death from altitude illness

High-Altitude Cerebral Edema (HACE)

Typical Onset: Usually follows untreated AMS; can be rapid
Altitude Threshold: Usually above 4,000 m (13,000 ft)
Cardinal Features: Truncal ataxia (earliest reliable sign), altered mental status, confusion, drowsiness progressing to coma
Severity: Life-threatening emergency

Syndrome	Typical Onset	Altitude Threshold	Cardinal Features	Severity
Acute Mountain Sickness (AMS)	6 to 12 hours after arrival	Above 2,500 m (8,200 ft)	Headache (required) plus nausea, vomiting, fatigue, dizziness, or sleep disturbance	Mild to moderate; self-limiting with rest
High-Altitude Pulmonary Edema (HAPE)	2 to 4 days after arrival	Usually above 3,000 m (10,000 ft)	Dyspnea at rest, dry cough progressing to productive cough with pink frothy sputum, exercise intolerance, cyanosis	Severe; leading cause of death from altitude illness
High-Altitude Cerebral Edema (HACE)	Usually follows untreated AMS; can be rapid	Usually above 4,000 m (13,000 ft)	Truncal ataxia (earliest reliable sign), altered mental status, confusion, drowsiness progressing to coma	Life-threatening emergency

The Lake Louise Acute Mountain Sickness Score (2018 revision) is the standard diagnostic tool for AMS:

Headache

0: None
1: Mild
2: Moderate
3: Severe, incapacitating

Gastrointestinal symptoms

0: None
1: Poor appetite or nausea
2: Moderate nausea or vomiting
3: Severe, incapacitating

Fatigue / weakness

0: None
1: Mild
2: Moderate
3: Severe, incapacitating

Dizziness / lightheadedness

0: None
1: Mild
2: Moderate
3: Severe, incapacitating

Symptom	0	1	2	3
Headache	None	Mild	Moderate	Severe, incapacitating
Gastrointestinal symptoms	None	Poor appetite or nausea	Moderate nausea or vomiting	Severe, incapacitating
Fatigue / weakness	None	Mild	Moderate	Severe, incapacitating
Dizziness / lightheadedness	None	Mild	Moderate	Severe, incapacitating

AMS is diagnosed when headache is present (score of at least 1) and the total score is 3 or greater in a person who has recently gained altitude.

An important clinical point: HAPE can occur without preceding AMS symptoms. A vignette may present a patient at altitude with isolated cough and dyspnea without prior headache. This is a tested distinction.

03Diagnostic Workup

Lake Louise Score

Role: Best initial assessment tool for AMS
Expected Findings: Total score of 3 or more with headache present confirms AMS

Pulse oximetry ( $S p O_{2}$ )

Role: Rapid bedside triage
Expected Findings: Disproportionately low $S p O_{2}$ relative to altitude (e.g., $S p O_{2}$ < 85% at 4,000 m where expected is ~88 to 90%)

Chest radiograph

Role: Confirms HAPE when clinical suspicion exists
Expected Findings: Bilateral, patchy alveolar infiltrates (often right middle lobe predominant early); normal cardiac silhouette

Arterial blood gas (ABG)

Role: Assesses oxygenation and acid-base status
Expected Findings: Low $P a O_{2}$ , respiratory alkalosis (low $P a C O_{2}$ , elevated pH) early; metabolic compensation over days

Brain MRI

Role: Most accurate test for HACE
Expected Findings: T2/FLAIR hyperintensity in white matter, characteristically the splenium of the corpus callosum and subcortical white matter

CT head

Role: Rapid assessment when MRI unavailable
Expected Findings: May show diffuse cerebral edema, but less sensitive than MRI for white matter changes

Test	Role	Expected Findings
Lake Louise Score	Best initial assessment tool for AMS	Total score of 3 or more with headache present confirms AMS
Pulse oximetry ( $S p O_{2}$ )	Rapid bedside triage	Disproportionately low $S p O_{2}$ relative to altitude (e.g., $S p O_{2}$ < 85% at 4,000 m where expected is ~88 to 90%)
Chest radiograph	Confirms HAPE when clinical suspicion exists	Bilateral, patchy alveolar infiltrates (often right middle lobe predominant early); normal cardiac silhouette
Arterial blood gas (ABG)	Assesses oxygenation and acid-base status	Low $P a O_{2}$ , respiratory alkalosis (low $P a C O_{2}$ , elevated pH) early; metabolic compensation over days
Brain MRI	Most accurate test for HACE	T2/FLAIR hyperintensity in white matter, characteristically the splenium of the corpus callosum and subcortical white matter
CT head	Rapid assessment when MRI unavailable	May show diffuse cerebral edema, but less sensitive than MRI for white matter changes

Altitude illness is fundamentally a clinical diagnosis. In a test setting, you will not be expected to order advanced imaging to diagnose AMS. The Lake Louise Score is the best initial diagnostic framework. The vignette will give you a patient with recent altitude gain, a headache, and at least one associated symptom.

For HAPE, the diagnosis is also clinical: dyspnea at rest, cough, and crackles in a person at altitude. If a chest radiograph is obtained (for example, in a field clinic), the expected finding is bilateral patchy infiltrates with a normal-sized heart, which distinguishes it from cardiogenic pulmonary edema. Echocardiography, if available, would show elevated pulmonary artery systolic pressure but normal left ventricular function and normal pulmonary capillary wedge pressure.

For HACE, the clinical hallmark is ataxia plus altered mental status in a person at altitude. A tandem gait test (heel-to-toe walking) is the best bedside screening maneuver and is highly sensitive for early HACE. MRI of the brain, when available, is the most accurate confirmatory test, showing characteristic white matter edema in the splenium of the corpus callosum. However, treatment (descent) should never be delayed for imaging.

The alveolar-arterial oxygen gradient ( $A\text{-}a\ gradient$ ) can be useful conceptually. In altitude illness, the $A\text{-}a\ gradient$ is normal in uncomplicated AMS (the hypoxemia is from low inspired $O_{2}$ , not a parenchymal problem). In HAPE, the gradient is elevated because alveolar flooding impairs gas exchange.

04Management and Treatment

AMS (mild)

First-Line Treatment: Stop ascent, rest at current altitude, acclimatize for 24 to 48 hours
Adjuncts: Acetazolamide 250 mg PO BID; analgesics (ibuprofen, acetaminophen) for headache
Prophylaxis: Acetazolamide 125 mg PO BID starting 1 day before ascent

AMS (moderate to severe)

First-Line Treatment: Descend at least 500 to 1,000 m
Adjuncts: Dexamethasone 4 mg PO/IM/IV every 6 hours; acetazolamide 250 mg PO BID
Prophylaxis: Same as above

HAPE

First-Line Treatment: Immediate descent (at least 1,000 m) plus supplemental $O_{2}$ (target $S p O_{2}$ > 90%)
Adjuncts: Nifedipine 30 mg extended-release PO every 12 hours
Prophylaxis: Nifedipine 30 mg ER PO every 12 hours, or tadalafil 10 mg PO BID starting 1 day before ascent

HACE

First-Line Treatment: Immediate descent (highest priority) plus supplemental $O_{2}$
Adjuncts: Dexamethasone 8 mg IV/IM/PO loading dose, then 4 mg every 6 hours
Prophylaxis: Dexamethasone 2 mg PO every 6 hours (or 4 mg every 12 hours) starting 1 day before ascent

When descent is impossible

First-Line Treatment: Portable hyperbaric chamber (Gamow bag) simulating descent of ~1,500 to 2,500 m
Adjuncts: Combine with appropriate medications above
Prophylaxis: Gradual ascent protocol (no more than 300 to 500 m elevation gain per day above 2,500 m with rest days every 3rd day)

Condition	First-Line Treatment	Adjuncts	Prophylaxis
AMS (mild)	Stop ascent, rest at current altitude, acclimatize for 24 to 48 hours	Acetazolamide 250 mg PO BID; analgesics (ibuprofen, acetaminophen) for headache	Acetazolamide 125 mg PO BID starting 1 day before ascent
AMS (moderate to severe)	Descend at least 500 to 1,000 m	Dexamethasone 4 mg PO/IM/IV every 6 hours; acetazolamide 250 mg PO BID	Same as above
HAPE	Immediate descent (at least 1,000 m) plus supplemental $O_{2}$ (target $S p O_{2}$ > 90%)	Nifedipine 30 mg extended-release PO every 12 hours	Nifedipine 30 mg ER PO every 12 hours, or tadalafil 10 mg PO BID starting 1 day before ascent
HACE	Immediate descent (highest priority) plus supplemental $O_{2}$	Dexamethasone 8 mg IV/IM/PO loading dose, then 4 mg every 6 hours	Dexamethasone 2 mg PO every 6 hours (or 4 mg every 12 hours) starting 1 day before ascent
When descent is impossible	Portable hyperbaric chamber (Gamow bag) simulating descent of ~1,500 to 2,500 m	Combine with appropriate medications above	Gradual ascent protocol (no more than 300 to 500 m elevation gain per day above 2,500 m with rest days every 3rd day)

For mild AMS, the next best step is simply to halt further ascent and rest at the current elevation. Most patients improve within 24 to 48 hours as acclimatization occurs. Acetazolamide accelerates this process by inhibiting carbonic anhydrase in the renal tubules, causing bicarbonate diuresis, which produces a mild metabolic acidosis. This metabolic acidosis stimulates the central respiratory drive, increasing ventilation and improving oxygenation. A key teaching point: acetazolamide does not mask symptoms, it treats the underlying pathophysiology. Dosing for treatment is 250 mg PO twice daily. For prophylaxis, 125 mg PO twice daily is sufficient, started 24 hours before ascent and continued for 2 days after reaching the target altitude.

Acetazolamide is a sulfonamide derivative. It is contraindicated in patients with a true sulfonamide allergy (anaphylaxis). In those patients, dexamethasone is the alternative prophylactic agent, dosed at 2 mg every 6 hours or 4 mg every 12 hours. Dexamethasone works by reducing vasogenic edema and stabilizing the blood-brain barrier, but unlike acetazolamide, it does not aid acclimatization. This means that once dexamethasone is stopped, the patient is still unacclimatized and vulnerable.

For HAPE, the single most important intervention is descent combined with supplemental oxygen. This is the answer if a vignette asks for the "next best step" in a patient at altitude with dyspnea, crackles, and pink frothy sputum. Nifedipine, a dihydropyridine calcium channel blocker, serves as a pulmonary vasodilator that reduces pulmonary artery pressure and reverses the pathological HPV. It is the drug of choice when descent is delayed or as an adjunct. Phosphodiesterase-5 (PDE-5) inhibitors such as tadalafil (10 mg BID) or sildenafil (50 mg every 8 hours) are alternatives for both prophylaxis and treatment. Importantly, dexamethasone alone is not effective for HAPE because the pathology is pulmonary vascular, not inflammatory cerebral edema. Diuretics are not used because the patient is typically already volume-depleted from altitude diuresis.

For HACE, immediate descent is the highest priority and is not negotiable. Dexamethasone is the pharmacologic cornerstone because it directly addresses vasogenic cerebral edema by stabilizing the blood-brain barrier. The loading dose is 8 mg followed by 4 mg every 6 hours. The Gamow bag (a portable hyperbaric chamber inflated by a foot pump) simulates descent by increasing ambient pressure around the patient and is used when physical descent is impossible due to weather, terrain, or darkness.

One important caveat for exams: acetazolamide has no role in treating HACE. It is too slow and too mild. The tested concept is recognizing that HACE demands dexamethasone and descent, not acetazolamide.

05Differential Diagnosis and Distractors

Migraine

Why It Is Similar: Headache, nausea, photophobia, and vomiting overlap heavily with AMS
Key Discriminator: Migraine typically has a prior history, aura, and unilateral throbbing quality. AMS headache is bilateral, worsens with exertion, and improves with descent. The context of recent altitude gain is the distinguishing feature

Dehydration / Exhaustion

Why It Is Similar: Headache, fatigue, dizziness, and nausea are common in both
Key Discriminator: Dehydration responds rapidly to oral rehydration and rest without descent. AMS symptoms persist despite hydration and worsen with continued altitude exposure

Carbon monoxide (CO) poisoning

Why It Is Similar: Headache, confusion, nausea at altitude (from cooking stoves in enclosed tents or shelters)
Key Discriminator: Cherry-red skin coloration, elevated carboxyhemoglobin on co-oximetry, symptoms affect multiple people in the same enclosed space simultaneously, improvement when removed from the enclosed environment

Pneumonia

Why It Is Similar: Cough, dyspnea, crackles, and infiltrates on chest radiograph overlap with HAPE
Key Discriminator: Pneumonia presents with fever and purulent sputum. HAPE has pink frothy (not purulent) sputum, no fever (or low-grade only), and the patient improves dramatically with descent and oxygen

Cardiogenic pulmonary edema

Why It Is Similar: Dyspnea, crackles, bilateral infiltrates on radiograph
Key Discriminator: Cardiogenic edema shows cardiomegaly, elevated BNP, bilateral pleural effusions, and Kerley B lines. HAPE shows a normal-sized heart, and echocardiography reveals normal left ventricular function with elevated pulmonary artery pressure

Meningitis / Encephalitis

Why It Is Similar: Headache, altered mental status, and neck stiffness can mimic HACE
Key Discriminator: Meningitis presents with high fever, nuchal rigidity, positive Kernig and Brudzinski signs, and CSF pleocytosis. HACE presents with ataxia as the earliest sign and occurs in the setting of recent altitude gain

Hypothermia

Why It Is Similar: Confusion, altered mental status, and poor coordination at altitude
Key Discriminator: Core body temperature is markedly low (< 35 C). Mental status changes correlate with temperature, not with altitude or duration of ascent. Rewarming improves symptoms

Differential	Why It Is Similar	Key Discriminator
Migraine	Headache, nausea, photophobia, and vomiting overlap heavily with AMS	Migraine typically has a prior history, aura, and unilateral throbbing quality. AMS headache is bilateral, worsens with exertion, and improves with descent. The context of recent altitude gain is the distinguishing feature
Dehydration / Exhaustion	Headache, fatigue, dizziness, and nausea are common in both	Dehydration responds rapidly to oral rehydration and rest without descent. AMS symptoms persist despite hydration and worsen with continued altitude exposure
Carbon monoxide (CO) poisoning	Headache, confusion, nausea at altitude (from cooking stoves in enclosed tents or shelters)	Cherry-red skin coloration, elevated carboxyhemoglobin on co-oximetry, symptoms affect multiple people in the same enclosed space simultaneously, improvement when removed from the enclosed environment
Pneumonia	Cough, dyspnea, crackles, and infiltrates on chest radiograph overlap with HAPE	Pneumonia presents with fever and purulent sputum. HAPE has pink frothy (not purulent) sputum, no fever (or low-grade only), and the patient improves dramatically with descent and oxygen
Cardiogenic pulmonary edema	Dyspnea, crackles, bilateral infiltrates on radiograph	Cardiogenic edema shows cardiomegaly, elevated BNP, bilateral pleural effusions, and Kerley B lines. HAPE shows a normal-sized heart, and echocardiography reveals normal left ventricular function with elevated pulmonary artery pressure
Meningitis / Encephalitis	Headache, altered mental status, and neck stiffness can mimic HACE	Meningitis presents with high fever, nuchal rigidity, positive Kernig and Brudzinski signs, and CSF pleocytosis. HACE presents with ataxia as the earliest sign and occurs in the setting of recent altitude gain
Hypothermia	Confusion, altered mental status, and poor coordination at altitude	Core body temperature is markedly low (< 35 C). Mental status changes correlate with temperature, not with altitude or duration of ascent. Rewarming improves symptoms

06Traps and High-Yield Pearls

The most common way students lose points on altitude sickness questions is by confusing the drug-to-syndrome pairing. Acetazolamide is for AMS prevention and treatment. Nifedipine is for HAPE. Dexamethasone is for HACE (and for AMS when acetazolamide is contraindicated or symptoms are moderate to severe). Students frequently select dexamethasone for HAPE or acetazolamide for HACE, both of which are incorrect first-line choices.

A second frequent trap involves a HAPE vignette that looks like pneumonia or heart failure. The test-writer will present a patient at altitude with cough, dyspnea, and bilateral infiltrates. The distractors will include antibiotics (for pneumonia) and furosemide (for heart failure). The correct answer is descent plus oxygen plus nifedipine. The clue is always the altitude context plus the normal cardiac silhouette plus the absence of fever and purulent sputum.

Another tested pearl: HAPE can present without prior AMS symptoms. If the vignette describes a climber who ascended rapidly and developed isolated cough and dyspnea without preceding headache, students may be confused because they expect the classic AMS-to-HAPE progression. HAPE can occur de novo.

Students should also remember that descent is the definitive treatment for all forms of altitude illness and always takes priority over pharmacotherapy. If a question asks for the single best next step, and descent is an option, it is almost always the answer for HAPE and HACE.

Finally, a pharmacology trap: acetazolamide is a sulfonamide. A vignette describing a patient with sulfonamide allergy planning a high-altitude trek will test whether you know to substitute dexamethasone for prophylaxis. Acetazolamide is contraindicated in this scenario, and the question will offer it as an answer choice. The tested concept here is recognizing the drug class cross-reactivity.

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