Altitude

Question 1

Patm at sea level?

Answer 1

~760mmHg

Question 2

O2% in atm?

Answer 2

21%

Question 3

PiO2 sea level?

Answer 3

160mmHg

Question 4

What decreases with altitude?

Answer 4

Patm

Question 5

What effect does falling Patm have on O2?

Answer 5

O2% stays at 21% BUT PiO2 falls

Question 6

What is alveolar PO2? Why lower than PiO2?

Answer 6

100mmHg at sea level, oxygen has been extracted by pulmonary blood.

Question 7

What is PaO2 why is it lower than alveolar PO2?

Answer 7

Due to a slight ventilation perfusion mismatch (0.8)

Question 8

Acclimatization vs adaptation?

Answer 8

Adaptation due to selection pressure over thousands of years, seen in communities living at high altitude

Acclimatization consists of physiological changes seen in all humans who ascend to altitude

Question 9

With every 5500m ascent, what happens to PiO2?

Answer 9

PiO2 roughly halves.

Question 10

Why does arterial saturation remain high until 2000m?

Answer 10

Due to plateau on oxyhemoglobin dissociation curve.

Question 11

When does saturation begin to fall significantly?

Answer 11

When PO2 falls below 60mmHg at 3000m.

Question 12

What are the main systems responding to altitude?

Answer 12

Respiratory, cardiovascular and endocrine

Question 13

When will one experience mountain sickness?

Answer 13

If one ascends slowly

Question 14

What are the initial respiratory changes occurring at altitude?

Answer 14

Hypoxic stimulation of peripheral arterial chemoreceptors

Resting hyperventilation - to raise PaO2 closer to PiO2,

Question 15

What is an immediate consequence of hyperventilation?

Answer 15

Reduces alveolar and arterial PCO2 - respiratory alkalosis

Question 16

What is the initial change to the haemoglobin curve?

Answer 16

Due to fall in CO2

Shifts haemoglobin curve to the left (reverse Bohr shift) enabling arterial blood to bind to more O2 at a given PO2.

Question 17

What happens to the haemoglobin curve at moderate to high altitude?

Answer 17

Respiratory alkalosis leads to a rise in 2,3BPG (formed during glycolysis in red blood cells). This binds to one of the beta chains of haemoglobin - deoxygenation and a right hand shift in the Bohr curve - improves O2 unloading to tissues.

Question 18

What limits the respiratory alkalosis?

Answer 18

Central chemoreceptors regulate ventilation according to CSF [H+] influenced by both PCO2 and HCO3-.

Reduction of CO2 during ventilation and resultant alkalosis limits ventilation via central chemoreceptors.

Question 19

How do we acclimatize to hyperventilation? (what was the traditional belief and what is the more modern belief?)

Answer 19

Traditionally attributed to correction of the respiratory alkalosis by the kidneys. Metabolic acidosis – renal response more long term (show on davenport diagram – metabolic acidosis).

But inadequate, because normalization of blood and CSF pH lag behind the ventilatory response.

Instead, in the short term, adaptation within both the peripheral and central chemoreceptors thought to contribute

Question 20

Why don’t we think the kidneys are responsible for hyperventilation acclimatisation?

Answer 20

Normalization of blood and CSF pH lag behind the ventilatory response.

Question 21

What happens to the chemoreceptors in altitude?

Answer 21

Central chemoreceptors become more sensitive to CO2

O2 threshold of the chemoreceptor drive is higher in acclimatized individuals - increased sensitivity of peripheral chemoreceptors.

Question 22

Acclimatization can only be achieved through…

Answer 22

hypoxic hypocapnia

Question 23

Response to O2 or CO2 more important for acclimatization?

Answer 23

Oxygen

Question 24

How is hypercapnia controlled long term?

Answer 24

By the kidneys

Question 25

How is hypercapnia reduced by kidneys?

Answer 25

Upregulation of HCO3- loss (type B intercalated cells)

Question 26

How does acetazolamide accelerate acclimatization? (2 ways)

Answer 26

Stimulating renal excretion of bicarbonate to counter the alkalosis - this stimulates the respiratory centre to increase the depth and frequency of respiration - speeding up natural acclimatization process. Shifts equation to left, facilitate loading of molecular CO2 to keep in the tissue (slow down reaction)– keep CO2 high enough around central chemoreceptors to prevent inhibitory drive.

Question 27

What happens in acute mountain sickness?

Answer 27

Raised pH and hypocapnia - Cerebral vasoconstriction - decrease in cerebral blood flow - lightheadedness and loss of consciousness.

Question 28

Why do you get acute mountain sickness?

Answer 28

Rapid ascent so reduced time to acclimatize

Question 29

What cardiovascular change is required in altitude? Why>

Answer 29

Arterial PO2 is low, blood to cell diffusion gradient falls - arteriovenous difference falls. So increase in CO is needed to maintain O2 to tissues

Question 30

How is raised CO brought about in acclimatization?

Answer 30

Raised cardiac output is brought about by a resting tachycardia of up to 100 per minute due to the withdrawal of vagal inhibition of the pacemaker.

Question 31

What happens to stroke volume in acclimatization?

Answer 31

Stroke volume falls during the first week at altitude and then tends to stabilize.   Acclimatization: After several weeks, CO returns to sea level values but SV remains reduced - chronic elevation in HR to accommodate this.

Question 32

What causes initial fall in SV?

Answer 32

The fall in stroke volume is associated with reduction in left ventricular dimensions and filling pressure

Question 33

Why is there reduced filling pressure at altitude?

Answer 33

Hypoxic diuretic response Initial decrease due to increased release of atrial natriuretic peptide and decreased synthesis of aldosterone Whereas the further reduction of plasma volume occurs without a net loss of body water by a fluid shift from the extracellular to the intracellular compartment.

Question 34

What happens to systemic and pulmonary pressure?

Answer 34

Systemic arterial pressure falls while pulmonary arterial pressure rises

Question 35

Why does systemic pressure fall?

Answer 35

Hypoxic reduction of peripheral resistance outweighs CO so systemic pressure falls Hypoxic diuresis

Question 36

How does pulmonary hypertension develop?

Answer 36

Pulmonary hypertension develops due to the raised CO and hypoxic pulmonary vasoconstriction.

Question 37

What is the advantage of hypoxic pulmonary vasocontstriction?

Answer 37

Redirects blood flow to the upper parts of the lung that are better ventilated (higher V/Q ratio) so helps match perfusion to ventilation in an upright position

Question 38

What happens to blood pressure in acclimatization?

Answer 38

Blood pressure and systemic vascular resistance then rise over at least 3 to 4 weeks because of increasing sympathetic activity and reduced tissue hypoxia associated with acclimatization.

Question 39

Is the red blood cell response short or long term?

Answer 39

Long term response

Question 40

What happens to RBC in acclimatization?

Answer 40

Polycythaemic response: O2 carrying capacity of blood is increased by a rise in haematocrit (up to 65%).

Question 41

What happens at haematocrit >0.65?

Answer 41

Chronic mountain sickness (Monge’s disease) can develop leading to reduced mental and physical capacity.

Question 42

What causes polycythaemic response?

Answer 42

Rise in RBC due to increased bone marrow erythropoiesis driven by release of erythropoietin (EPO).

Question 43

What is EPO produced by?

Answer 43

EPO is produced by interstitial fibroblasts in the kidney in close association with the PCT.

Question 44

Where is EPO produced in pre-natal period?

Answer 44

Liver

Question 45

How does EPO act?

Answer 45

Binds to EPO receptor on the red cell progenitor surface - differentiation, survival and proliferation of the erythroid cell.

Question 46

What does an increased Hb mean?

Answer 46

Increased O2 carrying capacity of the blood.

Question 47

How do EPO secreting cells sense O2?

Answer 47

HIF-1alpha accumulates in hypoxia, can bind HIF-1beta to increase transcription.