53.3 Life at High Altitude Flashcards
(31 cards)
What are some of the challenges of being at high altitude?
- Temperature
- Humidity
- Solar radiation
- Remoteness
- Hypoxia
At high altitudes, is there hypocapnia or hypercapnia?
Hypocapnia
What is acute mountain sickness?
[IMPORTANT]
- Sickness that occurs during an ascent, typically before you acclimatise
- Risk factors include:
- Speed of ascent
- Final altitude
- Individual predisposition
- Defined as headache and Lake Louise Score >3, in setting of recent ascent
What is high altitude cerebral oedema (HACE)? What are the symptoms and treatment?
- Severe swelling of the brain due to fluid.
- Symptoms:
- Headache, malaise, ataxia, confusion and coma
- Treatment:
- Descent
- Decompression
- Oxygen
- Dexamethasone [IMPORTANT]
What are the causes of high altitude cerebral pulmonary oedema?
- Hypoxia leads to increased cerebral blood flow, increased cerebral blood volume and increased permeability of the BBB
What is high altitude pulmonary oedema (HAPE)? What are the causes, symptoms and treatment?
- Severe swelling of the lungs due to fluid accumulation
- Causes:
- Widespread pulmonary vasoconstriction upon ascent to high altitudes
- Strong individual predisposition
- Leading cause of death at high altitudes
- Symptoms:
- Dry cough, then pink frothy sputum and progressive hypoxia
- Treatment:
- Descent
- Oxygen
- Nifedipine [IMPORTANT] -> Calcium channel blocker that reduces vasoconstriction
What is the treatment for altitude sickness?
- Altitude sickness -> Acetazolamide can be taken in advance to prepare:
- This is a carbonic anhydrase inhibitor
- It increases renal bicarbonate loss
- Therefore, it gives a head start to acclimatisation to high altitudes since renal excretion of bicarbonate is required for central chemoreceptor adaptation and it is usually slow
What is the treatment for high altitude cerebral oedema?
- High altitude cerebral oedema -> Dexamethasone:
- This is a steroid
- It acts to decrease inflammation and thus it prevents oedema, but the exact mechanism of action is not known
What is the treatment for high altitude pulmonary oedema?
- High altitude pulmonary oedema -> Nifedipine
- This is a calcium channel blocker, quite specific to the lungs
- It acts to decrease vasoconstriction of the lungs, which prevents oedema
What are the chronic haematological changes?
*↑regulation of erythropoietin
*Metabolic adaptations mediated by HIF (e.g. ↑ glycogen stores in Sk.muscle + changes to glucose metabolism)
What happens to HIF in normal conditions?
Normoxia → ↓ [HIF]. Von Hippel-Lindau protein (w/ its ubiquitin ligase activity) tags HIF-α for degradation by proteosome complex
What happens to HIF in hypoxic conditions and how does this allow it to regulate EPO?
Hypoxia → ROS production in Mit. inhibits prolyl hydroxylation of HIF-α by VDL-protein → HIF accumulation → TFs that bind to HRE in DNA → ↑-reg HRE expression (e.g. VEGF + EPO genes) → ↑ effector protein expression involved in O2 delivery + utilisation
What is EPO? Where is it synthesised and what is its effect?
Erythropoietin
*Synthesised by interstitial cells of renal cortex (main) + perisinusoidal liver cells + pericytes of brain
*Jak2 cascade signalling → EPO induces erythroid progenitor cells to differentiate into mature RBCs → ↑ haematocrit → ↑ O2 blood content
What can excessive polycythaemia lead to?
Excessive polycythaemia → ↑ blood viscosity → disrupts flow of blood through pulmonary capillaries → ↓ alveolar gaseous exchange → hypoxaemia.
What is polycythemia?
A condition where there is an increased number of RBCs.
What can cause polycythemia?
HIF upregulation (or other changes in the HIF pathway), which leads to increased EPO production and thus RBC production.
How does polycythaemia affect oxygen delivery to tissues?
Polycythemia slows blood flow, which decreases oxygen delivery to tissues.
What happens to pulmonary arterial pressure at high altitudes?
It increases due to vasoconstriction.
Why does pulmonary vasoconstriction occur and is it always helpful?
- It occurs in hypoxic areas of the lungs
- This preserves flow to better oxygenated parts of the lungs, optimising ventilation/perfusion matching
- This is useful when it is local (e.g. in pneumonia) but it is harmful when it is widespread (e.g. at altitude)
How does high altitude affect haemoglobin levels affected by altitude?
High altitude leads to high levels of haemoglobin.
Give an example of a maladaptive change that happens at high altitude.
Maladaptive changes: HPV → HAPE + CMS
*Hypoxia → systemic vasculature dilates + pulmonary vessels constrict
- Beneficial when hypoxia acute + localised to lungs (e.g. pneumonia) - allows V/Q mismatch to be corrected
- Chronic (e.g. high altitude/ COPD) → pathological. Can cause pulmonary vascular remodelling + pulmonary HT → fluids drawn from from blood to lung tissue parenchyma due to ↑ starling forces → High-altitude pulmonary oedema (HAPE)
What are the acute haematological changes?
*Dehydration at ↑ altitude → ↓ plasma vol → haemoconcentration ([Hb] ↑ relative to plasma vol → ↑ O2 carried in blood)
*Leftward (Bohr) shift in O2-dissociation curve
*Also rightward shift:
How does a Leftward (Bohr) shift in O2-dissociation curve happen and how is this beneficial?
Respiratory alkalosis + ↓ PaCO2 from hyperventilation → ↓ [H+] binding to Hb → ↑ Hb binding affinity for O2 → ↑ SaO2 at given PaO2 → ↑ loading efficiency
How does a Rightward (Bohr) shift in O2-dissociation curve happen and how is this beneficial?
E.g. 2,3-DPG production → ↑ RBC glycolysis (due to ↑regulation of erythropoietin) → ↓ Hb affinity for O2 → ↑ unloading efficiency.
