Respiratory Physiology

Question 1

What are the body’s long term adaptations to high altitude?

Answer 1

Increased erythropoeitin production to increase haemoglobin concentration
Angiogenesis in skeletal muscle
Renal excretion of bicarbonate to compensate for respiratory alkalosis
Increased mitochondria
Increased 2,3-DPG
Right ventricular hypertrophy and pulmonary hypertension

Question 2

What are the immediate compensatory mechanisms of the body in response to high altitude?

Answer 2

Hyperventilation
Tachycardia
Inhibition of digestion and redistribution of blood to vital organs

Question 3

What are the respiratory effects of altitude on the human body?

Answer 3

Reduced PaO2 leads to increased tidal volume and respiratory rate.

This excretes more CO2, further increasing the PAO2 via the alveolar gas equation.

This only works until the braking effect is seen.

This is when the alkalosis induced by hypocapnoea trigger central and peripheral chemoreceptors respectively and limit any further increase in minute ventilation.

In response to the persistent alkalosis, the kidneys compensate by excreting more bicarbonate.

The alkalosis also induces a left shift of the dissociation curve, leading to more 2,3-DPG production, which helps to shift it back to the right.

Question 4

What are the cardiovascular effects of altitude on the human body?

Answer 4

Hypoxic pulmonary vasoconstriction causes increased pulmonary vascular resistance and therefore increased right ventricular afterload.

It can also lead to pulmonary oedema
Increased heart rate due to sympathetic stimulation.

Pressure diuresis and increased respiratory losses due to hyperventilation lead to reduced plasma volume and therefore decreased preload, causing a reduction in stroke volume.

This also increases the haematocrit and the viscosity of blood, generating higher workload for the myocardium, and an increased thrombotic risk.

The stimulation of EPO production from the kidney to compensate for hypoxia further increases the haematocrit of the blood

Question 5

What effects on the body are seen due to the changes in temperature and humidity at altitude?

Answer 5

Reduced temperature
- Increased metabolic workload to maintain normothermia
- Vasoconstriction leads to increased preload and afterload
- Frostbite

Reduced humidity
- Increased dehydration from mucosal surfaces
- Increased heat loss as energy required to warm and humidify respiratory gases
- Both of these are worsened further by hyperventilation

Question 6

What factors increase 2,3-DPG production?

Answer 6

Chronic hypoxia
Anaemia
Altitude
Alkalosis
Exercise
Pregnancy
Hyperthyroidism

Question 7

How is 2,3-DPG produced and what does it do?

Answer 7

An organophosphate molecule produced during glycolysis in the red blood cell, 2,3 - Diphosphoglycerate causes a right shift in the oxygen dissociation curve to encourage unloading of oxygen into tissues.

It neatly allows the red blood cell to ‘choose’ between energy production and oxygen unloading, depending on the needs of the tissue it supplies.

The red blood cell can either continue the glycolysis pathway, producing 3-phosoglycerate, or it can produce 2,3-DPG and prioritise oxygen unloading instead.

Question 8

What are the causes of pulmonary hypertension?

Answer 8

Structural heart disease such as VSD and ASD

Respiratory disease such as COPD, recurrent pulmonary embolism

Collagen disorders

Kyphoscoliosis
Schistosomiasis