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What is Orthostatic Intolerance?

Orthostatic intolerance is the umbrella term for a range of different conditions that result in difficulty with the upright posture, particularly standing. The most dramatic problem people with orthostatic intolerance suffer is fainting, but in between fainting episodes they may feel weak, lightheaded, have palpitations or abnormal sweating, feel nauseated and experience problems with concentration.

When we go from lying to standing, gravity drags blood into our legs and pelvis. This movement of blood activates pressure receptors in the neck and chest and sends a message to our brain essentially saying ‘blood has gone south’. The normal response is to activate the nerves of our sympafthetic (fight or flight) nervous system. The nerve transmitter, noradrenaline, is then released from the nerves. This acts to tighten blood vessels in our legs, abdomen and pelvis so that blood is moved upwards against gravity and back to the heart. In additions there is a slight rise in the heart rate. All of this happens very quickly, usually in less than a second, so our blood pressure remains stable and our brain keeps getting a good blood supply when we move from lying to sitting or further to standing.

Who does it affect?

Two broad groups of people suffer from Orthostatic Intolerance.

Autonomic failure

This group are predominantly elderly people who have damage to the nerves or brain areas involved in this blood pressure stabilisation loop. This damage often occurs in association with other diseases such as Parkinson’s disease, Lewy Body Dementia, multiple system atrophy or diabetes. This group have blood pressure that is high when they lie down and falls very low when they stand up.

There is no cure for this form of orthostatic intolerance, but medications together with simple measures such as tensing the leg muscles to move blood back to the head, drinking a good amount of water and eating a high salt diet can help.

Blood pressure regulation

A much larger group of people suffer from forms of orthostatic intolerance that are due to a blood pressure regulation system that hasn’t failed, but isn’t working as effectively as it should. In these circumstances the brain and nerves pathways remain intact. The two most common conditions that fall into this category are:

Vasovagal syncope
Vasovagal syncope is the most common of these conditions and affects people of all ages, however symptoms most commonly begin in the teens and early 20s, occurring more commonly in women. The incidence then increases in frequency again as we enter our 60s. Some people with these conditions will suffer symptoms on a daily basis, whereas others will only experience symptoms in specific circumstances such as having blood taken, with prolonged standing, if it is very hot or they are dehydrated. Vasovagal syncope is common, affecting up to 40 per cent of the population at some time in their life, a subset of whom are severely affected, such that their condition affects their ability to work or study. In general people with these disorders are prone to pooling blood in their legs and pelvis, but for a condition that is so common, the underlying mechanisms remain poorly defined. Whilst many people will respond to simple measures such as leg tensing and high salt diet, together with a good fluid intake, others require special medications to tighten up blood vessels or to make them retain salt and fluid.

Postural Orthostatic Tachycardia Syndrome
The Postural Orthostatic Tachycardia Syndrome (POTS) is a more complex and less common condition that most commonly occurs in young women. It is associated with orthostatic intolerance in the presence of an inappropriate heart rate rise with the assumption of upright posture. Patients with this condition frequently suffer from non-posture related symptoms also including abdominal symptoms, fatigue, sleep disturbance and migraine.


Professor Murray Esler and researchers at Baker IDI have been working to understand more about the underlying mechanisms in patients with different forms of orthostatic intolerance. Baker IDI research has concentrated on better defining clinical subgroups with these disorders, followed by detailed assessment of the sympathetic (fight or flight) nervous system. This work recently led to a trial of a novel medication in patients with vasovagal syncope. Further research is needed to allow a better understanding of what causes these conditions so that targeted therapies can be developed.

Further research is needed to allow a better understanding of what causes these conditions so that targeted therapies can be developed.

Related research papers

Epigenetic modification of the norepinephrine transporter gene in Postural Tachycardia Syndrome
Bayles, R. et al., 2012

Management strategies for recurrent vasovagal syncope
Vaddadi, G. et al., 2010

Altered sympathetic nervous reactivity and norepinephrine transporter expression in patients with Postural Tachycardia Syndrome
Lambert, E. et al., 2008

Vasovagal syncope – the electricity, the pump or the input pressure?
Corcoran, S. & Lambert, E., 2012

Support the Greg Page Fund

The Greg Page Fund for Orthostatic Intolerance was established to raise much needed funding to support Baker IDI’s research.

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