• Gravity induced pooling of blood in lower extemities on standing compremises venous return and therefore preload, reducing cardiac output and therefore arterial blood pressure
• Baroreceptor reflex (see card) causes vasoconstriction and increased cardiac contractility to ameloriate loss of cranial perfusion to such an extent that diastolic blood pressure temporarily overshoots normal physiolgical ranges
• Low pressure baroreceptors in larges systemic veins, pulmonary vessels and atrium also contribute afferents to brainstem and result in sympathoexcitation

• Blood gases do not change considerably, so peripheral and central chemoreceptors do not play a large role (some peripheral effects to increase breathing rate)
• Phase I breathing - central command and feedforward control from learnt behaviour
• Afferent signals from muscle to produce feedback control
• Oscillations in Pa_CO2 - may be detected by peripheral chemoreceptors
• Lactate, potassium and adrenaline buildup as stimulation of peripheral chemoreceptors 
• Release of NAd from superior, middle and inferior cardiac nerves to increase HR and contractility
• Local vasodilation from potassium, hydrogen ion, ADP and low P_o2, as well as circulating adrenaline

• O₂ consumption - each ml associated with 20J of work energy (basal 83J/sec or Watt, exercise 567W), only 22% useful in exercise
• CO₂ production can be used as a measure of work done 
• Metabolic rate can be defined as the combination of work and heat output

• Glucose yields 36-39 ATP per molecule (2-3 in anaerobic respiration (3.75 calories per gram)
• Fatty acids yield 16 ATP per CH₂-CH₂ subunit (9 calories per gram)
• Protein - 4 calories per gram
• The respiratory quotient = CO₂ eliminated/O₂ consumed - form of indirect calorimetry (carbohydrates 1, protein 0.8-0.9, fats 0.7)

• Lower oxygen partial pressure without an increase in carbon dioxside partial pressure
• Correction of oxygen blows off CO₂ - counteraction of low O₂ effect
• Therefore hyperventilation lowers CO₂ - phase of acquisition of lower CO₂ tolerance to allow increased ventilation - mediated by chemoreceptor (peripheral) set point resetting
• Unchecked hyperventiliation can now cause alkalosis - kidneys required to excrete more base (type II intercalated cells)

Long term adaptations to life at high altitude

(HIF and EPO)

• In normoxia, HIF α subunits are hydroxylated at proline residues by HIF prolyl-hydroxylases allowing recognition and ubiquitination by VHL E3 ubiquitin ligase and therefore degredation in the proteasome
• In hypoxia, HIF prolyl-hyroxylase is inhibited as O₂ is used as a substrate, allowing HIF translocation into the nucleus and associate with transcriptional coactivators to allow the upregulation of VEGF and EPO to induce neovascularisation and haematopoiesis respectively 

Types of altitude sickness

• Acute mountain sickness - breathlessness and dizziness from hypoxic pulmonary vasocontriction and alkalosis from blow off of CO₂
• Hypoxaemia results in increased cerebral blood flow, increased capillary pressure, increased cerebral blood volume and increased BBB pemeability - and therefore brain swelling
• Inadequate buffering by CSF can result in AMS, which progresses to high altitude cerebral edema. 
• Blunted hypoxic ventilatory response results in alveolar hypoxia. Alveolar hypoxia, combined with a strong hypoxic pulmonary vasoconstriction response, sympathetic overactivity, endothelial dysfunction, genetics, cold and/or exercise results in raised pulmonary hypertension
• Raised pulmonary hypertension increases capillar pressure, causes endothelial stress, and therefore capillary leakage (augmented if infection present). Capillary leakage (augmented by decreased alveolar clearance of sodium and water and/or inflammation) results finally in high-altitude pulmonary oedema

• Eosinophilic (atopic asthma) - allergen triggers activation of mast cells and lymphocutes, which in turn activates GM-CSF and eosinophil activity factor, permitting an eosinophilic response
• Non-eosinophilic (non-atopic asthma) - epithelial cells and macrophages produce GM-CSF in presence of virus or pollution, triggering neutrophil activity factor, leading to neutrophil proliferation and activation and therefore asthma

• Myocardium -1st degree heart block (increased R-R and P-R interval), leading to total heart block (massive R-R interval with slow, regular P waves independent of QRS). Effect due to inactivation of voltage gated calcium, sodium and potassium ion channels, while contractility decreased by effect on calcium leak from SR
• Vasodilator effect of volatile anaesthetics - action on DHP calcium channels blockade
• Decrease sympathetic nerve activity
• Depression of ventilation response in response to hypoxia as well as loss of pharyngeal dilator tone (and therefore loss of airway patency)