Hypoxemia and High Altitude Physiology

• Hypoxia is reduced oxygen delivery to tissues, while hypoxemia is reduced partial pressure of oxygen in blood, and ischemia is reduced blood flow to tissues.

Hypoxemia

• Normal A-a gradient is caused by low FiO2 (high altitudes) and hypoventilation.
• Increased A-a gradient is caused by V/Q mismatch, right-to-left shunt, and diffusion limitation.
• PaO2 does NOT correct with oxygen in shunt.
• Altitude causes hypoxemia (reduced Hb saturation) and hypoxia (reduced O2 delivery to tissues).

Adaptive Responses to High Altitude

• At high altitude, barometric pressure and alveolar PO2 decrease.
• Ventilation rate increases
• Arterial blood PaO2 decreases, pH increases (respiratory alkalosis), and RBCs increase.
• Pulmonary resistance and pulmonary artery pressure rises, causing hypertrophy of right ventricle.
• The O2-hemoglobin curve shifts to the right resulting in increased 2,3-DPG, P50, and decreased affinity for O2.
• A decrease in pH, increase in CO2, or increase in temperature will shift the Hb-saturation curve to the right (Bohr effect).
• Physiological responses to high altitude includes rise of cerebral blood flow, increased ventilation and pulmonary-artery pressure, increased heart rate and cardiac output, and increased stroke volume.
• Physiological responses to high altitude includes decreased plasma volume, bicarbonaturia, and EPO, rise of RCM, and Hb.
• Acute Mountain Sickness (AMS) can occur above 2500 m.
• Traveling above 3000 m (10,000 ft), travelers should not increase sleeping elevation by more than 500 m per night, with a rest day every 3 to 4 days.

High Altitude Diseases

• AMS: Hypoxemia and respiratory alkalosis during rapid ascent causes headache, insomnia, nausea, dizziness, fatigue, and anorexia; symptoms resolve in 24-48 hours
• Cerebral Edema (HACE): "end stage AMS"; rare and more likely over 4000 m; patients exhibit ataxia, altered mental status; mechanism likely to be increased cerebral capillary hydrostatic pressure due to increased hypoxic cerebral blood flow.
• Pulmonary Edema (HAPE): vigorous hypoxic pulmonary vasoconstriction; may develop 2-4 days after ascent.
• Acute mountain sickness risk begins above 2500 m.
• 32% of climbers have hallucinations above 7500 m.
• MRI changes, including white matter hyperintensities and cortical atrophy above 7000 m.
• Commercial aircraft are pressurized to an altitude equivalent of 1500-2500 m.

Clinical Problems at High Altitude

• High-altitude headache: Common above 2500 m with Onset within 4-24 hr after ascent, Stop ascent and rest at current elevation. Use NSAIDs or acetaminophen.
• Acute mountain sickness: Common above 2500 m with Onset within 1–2 days after ascent.Stop ascent and rest at current elevation. Use NSAIDs or acetaminophen for headache; antiemetics if needed
• High-altitude cerebral edema Unusual below 3500 m unless accompanied by high-altitude pulmonary edema. Onset within first few days after ascent; preceded by symptoms of acute mountain sickness, Descend if feasible; otherwise, use supplemental oxygen or portable hyperbaric chamber and Dexamethasone.
• High-altitude pulmonary edema Unusual below 3000 m with Onset 2-4 days after ascent, descends, use supplemental oxygen or portable hyperbaric chamber.
• Central sleep apnea Very common above 2500 m with Onset during first night at high altitude may persist with continued stay or further ascent, Descent not necessary and use acetazolamide, or nocturnal oxygen
• Acetazolamide increases bicarbonate excretion and induce mild metabolic acidosis, which helps sustain high ventilation at altitude.

Causes of Hypoxia

• Hypoxic hypoxia is caused by low PBarom or FiO2 (< 0.21) due to Altitude, O2 equipment error
• Alveolar hypoventilation occurs due to Drug overdose, COPD exacerbation
• Pulmonary diffusion defect is caused by Emphysema, pulmonary fibrosis
• Pulmonary V/Q mismatch is caused by Asthma, pulmonary emboli
• Circulatory hypoxia is caused by reduced cardiac output, or Congestive heart failure, myocardial infarction, dehydration
• Hemic hypoxia is caused by Reduced hemoglobin content due to Anemias
• Hemic hypoxia is caused by Reduced hemoglobin function due to Carboxyhemoglobinemia, methemoglobinemia
• Demand hypoxia is caused by increased Oxygen consumption, due to Fever, seizures
• Histotoxic hypoxia is caused by the Inability of cells to utilize oxygen, due to Cyanide toxicity
• Cyanosis is increased deoxyHb producing bluish skin/mucous membranes

Cyanide Poisoning

• Cyanide gas is a component of industrial fires (plastics, chemicals) or found in smoke from house fires, and cyanide is also produced from metabolism of nitroprusside (a nitrate).
• Cyanide inactivates cytochrome oxidase uncoupling cellular oxidation from phosphorylation of ADP making it lethal.
• Cells cannot use oxygen, so skin may be cherry red, venous O2 saturation is elevated, and severe lactic acidosis (above 10 mmol) will occur.
• Because cyanide has high affinity for methemoglobin, patients may be given nitrites to treat cyanide poisoning.
• Nitrites oxidize Hb forming MetHb & cyanide binds MetHb instead of cytochrome oxidase, then give sodium thiosulfate to convert the cyanide to thiocyanate (harmless and excreted in urine).
• Cherry-red appearance may be seen in cyanide poisoning.
• Cyanide-poisoned patients lack the prominent cholinergic signs seen in nerve agent poisoning, such as miosis and increased secretions
• If cyanide poisoning is the result of prolonged nitroprusside infusion, give hydroxocobalamin, or sodium thiosulfate if hydroxocobalamin is unavailable. Avoid the use of sodium nitrite as it may aggravate hypotension.

Methemoglobinemia

• Oxidized (Fe+3; ferric state) iron in MetHb does not bind oxygen; can be caused by mutations (Blue people of Kentucky) and induced by drugs
• In methemoglobinemia, blood appears chocolate brown (looks cyanotic).
• PaO2 is normal, resulting in hypoxia without hypoxemia.
• Tissue hypoxia is more severe than comparable levels of anemia and This is due to left-shift of Hb-oxygen saturation curve relative to anemia.
• Treat with IV methylene blue or ascorbic acid.
• Drugs such as anesthetics (lidocaine, benzocaine, and prilocaine) are commonly used can cause methemoglobinemia

Carbon Monoxide Poisoning

• Carboxyhemoglobinemia can happen after exposures to portable generators, fire, or engines
• Hb bound to CO is called carboxyhemoglobin, which is easily detected with CO-oximetry.
• The arterial and venous blood is dark.
• Heme groups bound to CO can not bind oxygen, which reduces O2 carrying capacity.
• Carboxyhemoglobin does not release oxygen at low PO2, and the shift is left of the dissociation curve
• CO poisoning Treatment: 100% oxygen will inhibit CO competitvely
• Hyperbaric chamber (Increasing PB over 760 mmHg, increasing PaO2 to up to at least 1800 and dissolved oxygen increases to 5-6 mL/dL

This lesson covers hypoxemia, its causes such as low FiO2 and V/Q mismatch, and adaptive responses to high altitude. It also highlights changes in ventilation rate, arterial blood, and the O2-hemoglobin curve. A-a gradient is also explored.