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==Causes==
==Causes==
'''[[Cardiorespiratory fitness|Cardiorespiratory Disorders]]:'''
Exercise intolerance is primarily found in cardiorespiratory disorders. It is also a common symptom in [[chronic fatigue syndrome]]. Several heart conditions, such as a [[cardiac arrhythmia]] (abnormal heart rate or rhythm) or an [[aortic valve insufficiency]], if severe enough can cause activity problems such as shortness of breath and/or exercise intolerance. People with acute back pain from an injury or chronic back pain (e.g., from a degenerative condition) may also experience exercise limitations due to muscle spasms or limited range of spinal motion. [[Overtraining]] and (undiagnosed) [[anemia]] can also cause the intolerance. Exercise intolerance may result from mutations in [[mitochondrial]] [[Coenzyme_Q_-_cytochrome_c_reductase|Complex III]], a complex of Co-enzyme Q10 ([[ubiquinol]]) and several proteins. Ubiquinol depletion caused by statin drug usage may also lead to muscle fatigue or exercise intolerance in some cases.<ref>{{cite journal|last=Thibault|first=A|author2=et al.|title=Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer|journal=Clin Cancer Res.|date=March 1996|volume=2|issue=3|pages=483–91|pmid=9816194|url=http://clincancerres.aacrjournals.org/content/2/3/483.full.pdf|accessdate=5/8/2012}}</ref>
# <u>[[Cystic fibrosis|cystic fibrosis (CF);]] </u> CF can cause skeletal muscle atrophy however more commonly it can cause exercise intolerance. The exercise intolerance is associated with reduced pulmonary function that is the origin of CF.<ref>{{Cite journal|url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599254/?tool=pmcentrez|title = Infection, inflammation and exercise in cystic fibrosis|last = Van de Weert-van Leeuwen|first = Pauline|date = 2013|journal = Bio Med Central|doi = 10.1186/1465-9921-14-32|pmid = |access-date = 13/04/2015}}</ref>
# <u>[[Bronchiectasis|bronchiectasis;]]</u>
# <u>[[spinal muscular atrophy|spinal muscular atrophy;]]</u>[[spinal muscular atrophy| ]] symptoms include exercise intolerance, cognitive impairment and fatigue.<ref>{{Cite journal|url = http://bv8ja7kw5x.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info:sid/summon.serialssolutions.com&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Motor+Neuron+Syndrome+as+a+New+Phenotypic+Manifestation+of+Mutation+9185T%3EC+in+Gene+MTATP6&rft.jtitle=Case+Reports+in+Neurological+Medicine&rft.au=Brum%2C+Marisa&rft.au=Semedo%2C+Cristina&rft.au=Guerreiro%2C+Rui&rft.au=Pinto+Marques%2C+José&rft.date=2014&rft.issn=2090-6668&rft.eissn=2090-6676&rft.volume=2014&rft.spage=1&rft.epage=4&rft_id=info:doi/10.1155%2F2014%2F701761&rft.externalDBID=n%2Fa&rft.externalDocID=10_1155_2014_701761&paramdict=en-au|title = Motor Neuron Syndrome as a New Phenotypic Manifestation of Mutation 9185T>C in Gene MTATP6|last = Brum|first = Marisa|date = 2014|journal = Case Rep Neurol Med|doi = 10.1155/2014/701761|pmid = |access-date = 13/04/2015}}</ref>
'''[[Chronic Fatigue Syndrome|Chronic Fatigue Syndrome (CFS):]]'''
* [[orthostatic intolerance]] occurs in CFS. [[orthostatic intolerance]] includes exercise intolerance as one of the main symptoms. It also includes fatigue, nausea, headaches, cognitive problems and visual disturbances as other less major symptoms. <ref>{{Cite journal|url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956649/|title = Predictors of post-infectious chronic fatigue syndrome in adolescents|last = Leonard|first = Jason|date = 1/01/2014|journal = Health Psychology and Behavioural Medicine|doi = 10.1080/21642850.2013.869176|pmid = |access-date = 14/04/2015}}</ref>
'''[[Post-concussion syndrome|Post-concussion Syndrome (PCS):]]'''
* exercise intolerance is present in those with PCS however their intolerance to exercise may reduce over time.<ref>{{Cite journal|url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784364/?tool=pmcentrez|title = Exercise Intolerance in Individuals With Postconcussion Syndrome|last = Kozlowski|first = Karl F.|date = 2013|journal = Journal of athletic training|doi = 10.4085/1062-6050-48.5.02|pmid = |access-date = 14/04/2015}}</ref>
⚫
* Individuals with [[Postconcussion syndrome|Postconcussion Syndrome (PCS)]] may also experience a level of exercise intolerance, however there is little known comparatively about exercise intolerance in PSC patients. <ref>{{Cite journal|url = |title = Exercise Intolerance in Individuals With Postconcussion Syndrome|last = Kozlowski|first = Karl F|date = 2013|journal = Journal of Athletic Training|doi = 10.4085/1062-6050-48.5.02|pmid = |access-date = |first2 = James|last2 = Graham|publisher = National Athletic Trainers Association|issue = 5|volume = 48|pages = 627-635}}</ref>
'''[[Heart Conditions]]: '''
# <u>[[cardiac arrhythmia|cardiac arrhythmia;]]</u>
# <u>[[Aortic valve insufficiency|aortic valve insufficiency;]]</u>
# <u>[[cardiac arrhythmia;aortic valve insufficiency;pulmonary artery hypertension (PAH);|pulmonary artery hypertension (PAH);]] </u> PAH has the following symptoms; dyspnea and fatigue, these systems consequently contribute to exercise intolerance. <ref>{{Cite journal|url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377355/?tool=pmcentrez|title = Exercise Intolerance in Pulmonary Arterial Hypertension|last = Fowler|first = Robin|date = 2012|journal = Pulmonary Medicine|doi = 10.1155/2012/359204|pmid = |access-date = 13/04/2015}}</ref>
# <u>[[asymptomatic atrial septal|asymptomatic atrial septa]]<nowiki/>l; </u> In the heart the right ventricular (RV) can have a volume overload which ultimately produces a pressure overload in the RV resulting in exercise intolerance as the RV is no longer able to control high pressure associated with exercise. <ref>{{Cite journal|url = http://bv8ja7kw5x.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info:sid/summon.serialssolutions.com&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Atrial+septal+defects&rft.jtitle=The+Lancet&rft.au=Tal+Geva&rft.au=Jose+D+Martins&rft.au=Rachel+M+Wald&rft.date=2014-05-31&rft.pub=Elsevier+Limited&rft.issn=0140-6736&rft.eissn=1474-547X&rft.volume=383&rft.issue=9932&rft.spage=1921&rft_id=info:doi/10.1016%2FS0140-6736%2813%2962145-5&rft.externalDocID=3319731811&paramdict=en-au|title = Atrial septal defects|last = Geva|first = Professor Tal|date = 2014|journal = The Lancet|doi = 10.1016/S0140-6736(13)62145-5|pmid = |access-date = 13/04/2015}}</ref>
'''Chronic Back Pain/acute back pain: '''


'''Anaemia:'''
⚫
Individuals with [[Postconcussion syndrome|Postconcussion Syndrome (PCS)]] may also experience a level of exercise intolerance, however there is little known comparatively about exercise intolerance in PSC patients. <ref>{{Cite journal|url = |title = Exercise Intolerance in Individuals With Postconcussion Syndrome|last = Kozlowski|first = Karl F|date = 2013|journal = Journal of Athletic Training|doi = 10.4085/1062-6050-48.5.02|pmid = |access-date = |first2 = James|last2 = Graham|publisher = National Athletic Trainers Association|issue = 5|volume = 48|pages = 627-635}}</ref>


'''Overtraining:'''
⚫
<nowiki> </nowiki>Exercise tolerance reflects the combined capacity of components in the oxygen cascade to supply adequate oxygen for ATP resynthesis. In individuals with diseases such as cancer, certain therapies can affect one or more components of this cascade and therefore reduce the body's ability to utilise or deliver oxygen, leading to exercise intolerance.<ref>{{Cite journal|title = Exercise intolerance in cancer and the role of exercise therapy to reverse dysfunction|url = http://linkinghub.elsevier.com/retrieve/pii/S1470204509700312|journal = linkinghub.elsevier.com|access-date = 2015-04-13|first = Lee W|last = Jones|last2 = Eves|first2 = Neil D}}</ref>

'''Mutations:'''
# <u>[[mitochondrial complex 111|mitochondrial complex 111;]]</u> Currently it is suggested that there are 27 different mutations identified in cytochrome ''b ''(mitochondrial complex III is one of those mutations). This mutation can often lead to skeletal muscle weakness and as a result exercise intolerance.<ref>{{Cite journal|url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2427202/|title = Mitochondrial Complex III Deficiency Associated with a Homozygous Mutation in UQCRQ|last = Barel|first = Ortal|date = 2008|journal = the American Journal Of Human Genetics|doi = 10.1016/j.ajhg.2008.03.020|pmid = |access-date = 14/04/2014}}</ref>
# <u>[[a complex of Co-enzyme Q10]];</u>
# <u>[[several proteins]];</u>
# <u>[[Skeletal muscle respiratory chain defect]]; </u> This can result in serve exercise intolerance which is manifested by the following symptoms of Skeletal muscle respiratory chain defect; muscle fatigue and lactic acidosis.<ref name=":0">{{Cite journal|url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC303965/?tool=pmcentrez|title = Exercise intolerance, lactic acidosis, and abnormal cardiopulmonary regulation in exercise associated with adult skeletal muscle cytochrome c oxidase deficiency.|last = Haller|first = R.G|date = 1989|journal = the journal of clinical investigation|doi = 10.1172/JCI114135|pmid = |access-date = 14/04/2015}}</ref>

⚫
* Exercise tolerance reflects the combined capacity of components in the oxygen cascade to supply adequate oxygen for ATP resynthesis. In individuals with diseases such as cancer, certain therapies can affect one or more components of this cascade and therefore reduce the body's ability to utilise or deliver oxygen, leading to exercise intolerance.<ref>{{Cite journal|title = Exercise intolerance in cancer and the role of exercise therapy to reverse dysfunction|url = http://linkinghub.elsevier.com/retrieve/pii/S1470204509700312|journal = linkinghub.elsevier.com|access-date = 2015-04-13|first = Lee W|last = Jones|last2 = Eves|first2 = Neil D}}</ref>


=== Cytochrome b mutations ===
=== Cytochrome b mutations ===
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== Cases ==
== Cases ==
'''<u>Case 1</u>'''
⚫
A 22-year old active male marine presented himself for care after experiencing exercise intolerance for over 4 months. This was preventing him from completing a standard 3 mile run as part of a general fitness test. He reported shortness of breath and fatigue while participating in minimal physical activity. Despite previously taking numerous medications the symptoms did not cease.

⚫
<nowiki> </nowiki>A 22-year old active male marine presented himself for care after experiencing exercise intolerance for over 4 months. This was preventing him from completing a standard 3 mile run as part of a general fitness test. He reported shortness of breath and fatigue while participating in minimal physical activity. Despite previously taking numerous medications the symptoms did not cease.


After numerous medical examinations the marine was found to have moderate restrictive lung disease, reduced lung capacity and moderate asthma with air trapping.
After numerous medical examinations the marine was found to have moderate restrictive lung disease, reduced lung capacity and moderate asthma with air trapping.


Treatment was conducted including a diagnostic and staging work-up with bone marrow biopsy and CT of the abdomen. He was also put through chemotherapy with doxorubicin, bleomycin, vinblastine and darcabazine. The treatment estimated a 90% recovery rate. He is expected to return to physical activity and his duties after completion of the chemotherapy.
Treatment was conducted including a diagnostic and staging work-up with bone marrow biopsy and CT of the abdomen. He was also put through chemotherapy with doxorubicin, bleomycin, vinblastine and darcabazine. The treatment estimated a 90% recovery rate. He is expected to return to physical activity and his duties after completion of the chemotherapy.

<u>'''Case 2'''</u>

the case involved a female of 27 years who had a lifelong severe exercise intolerance manifested by muscle fatigue, [[lactic acidosis]], and prominent symptoms of [[dyspnea]] and [[tachycardia]]. all of which were induced by minimal exercise. She was found to have a skeletal muscle respiratory chain defect characterized by low levels of cytochromes

An Investigation of the pathophysiology the women's exercise response revealed low maximal oxygen uptake (1/3 compared to a normal sedentary women). The findings also showed that impaired [[oxidative phosphorylation]] in working muscle disrupted the normal regulation of cardiac output and ventilation rate during exercise.<ref name=":0" />


==References==
==References==

Revision as of 12:34, 15 April 2015

A 70 year old man with exercise intolerance

Exercise intolerance is a condition where the patient is unable to do physical exercise at the level or for the duration that would be expected of someone in his or her general physical condition, or experiences unusually severe post-exercise pain, fatigue, nausea, vomiting or other negative effects. Exercise intolerance is not a disease or syndrome in and of itself, but a symptom.

Since there are many possible specific reasons why exercise could be inhibited, this is a rather slippery term. For instance, the patient may experience unusual breathlessness (dyspnea), muscle pain (myalgia), tachypnoea (abnormally rapid breathing), tachycardia (having a heart rate that exceeds the normal range) or increasing muscle weakness while exercising, or may, after exercise, experience severe headache, nausea, dizziness, occasional muscle cramps or extreme fatigue.

In most cases, the specific reason that exercise is not tolerated is of considerable significance when trying to isolate the cause down to a specific disease.

Causes

Cardiorespiratory Disorders:

  1. cystic fibrosis (CF); CF can cause skeletal muscle atrophy however more commonly it can cause exercise intolerance. The exercise intolerance is associated with reduced pulmonary function that is the origin of CF.[1]
  2. bronchiectasis;
  3. spinal muscular atrophy; symptoms include exercise intolerance, cognitive impairment and fatigue.[2]

Chronic Fatigue Syndrome (CFS):

Post-concussion Syndrome (PCS):

  • exercise intolerance is present in those with PCS however their intolerance to exercise may reduce over time.[4]
  • Individuals with Postconcussion Syndrome (PCS) may also experience a level of exercise intolerance, however there is little known comparatively about exercise intolerance in PSC patients. [5]

Heart Conditions:

  1. cardiac arrhythmia;
  2. aortic valve insufficiency;
  3. pulmonary artery hypertension (PAH); PAH has the following symptoms; dyspnea and fatigue, these systems consequently contribute to exercise intolerance. [6]
  4. asymptomatic atrial septal; In the heart the right ventricular (RV) can have a volume overload which ultimately produces a pressure overload in the RV resulting in exercise intolerance as the RV is no longer able to control high pressure associated with exercise. [7]

Chronic Back Pain/acute back pain:

Anaemia:

Overtraining:

Mutations:

  1. mitochondrial complex 111; Currently it is suggested that there are 27 different mutations identified in cytochrome b (mitochondrial complex III is one of those mutations). This mutation can often lead to skeletal muscle weakness and as a result exercise intolerance.[8]
  2. a complex of Co-enzyme Q10;
  3. several proteins;
  4. Skeletal muscle respiratory chain defect; This can result in serve exercise intolerance which is manifested by the following symptoms of Skeletal muscle respiratory chain defect; muscle fatigue and lactic acidosis.[9]
  • Exercise tolerance reflects the combined capacity of components in the oxygen cascade to supply adequate oxygen for ATP resynthesis. In individuals with diseases such as cancer, certain therapies can affect one or more components of this cascade and therefore reduce the body's ability to utilise or deliver oxygen, leading to exercise intolerance.[10]

Cytochrome b mutations

Cytochrome b mutations can frequently cause isolated exercise intolerance and myopathy and in some cases multisystem disorders. The mitochondrial respiratory chain complex III catalyses electron transfer to cytochrome c. Complex III is embedded in the inner membrane of the mitochondria and consists of 11 subunits. Cytochrome b is encoded by the mitochondrial DNA which differs from all other subunits which are encoded in the nucleus. Cytochrome b plays a major part in the correct fabricating and function of complex III.

This mutation occurred in an 18 year old man who had experienced exercise intolerance for most of his adolescence. Symptoms included extreme fatigue, nausea, a decline in physical activity ability and myalgia.

Treatment

Exercise is key for many heart and back patients, and a variety of specific exercise techniques are available for both groups. Some exercise specialists are trained in modifications specific to these patients[who?].

In individuals with heart failure and normal EF (ejection fraction), including aortic distensibility, blood pressure, LV diastolic compliance and skeletal muscle function, aerobic exercise has the potential to improve exercise tolerance. A variety of pharmacological interventions could potentially improve exercise tolerance in these individuals as well. [11]

Research on individuals suffering from Chronic obstructive pulmonary disease (COPD), has found a number of effective therapies in relation to exercise intolerance. These include:

  1. Oxygen Supplementation
    • Reduces carotid body drive and slows respiration at a given level of exercise.
  2. Treatment with bronchodilators
    • Clinically useful improvements in expiratory airflow, allows fuller exhalation in a given period of time, reduces dynamic hyperinflation, and prolongs exercise tolerance.
  3. Heliox (79% Helium, 21% oxygen)
    • Heliox has a lower density than air.
    • Breathing heliox lowers expiratory airflow resistance, decreases dynamic hyperinflation, and prolongs exercise tolerance.
  4. High intensity rehabilitative exercise training
    • Increasing the fitness of muscles decreases the amount of lactic acid released at any given level of exercise.
    • Since lactic acid stimulates respiration, after rehabilitative training exercising, ventilation is lower, respiration is slowed, and dynamic hyperinflation is reduced.

A combination of these therapies (Combined therapies), have shown the potential to improve exercise tolerance as well. [12]

Hazards

Certain conditions in particular exist where exercise, particularly rehabilitation, may be contraindicated, including:

Other conditions may also preclude exercising under certain conditions. Passive physiotherapy can in some instances be an alternative for some patients unable to safely self-power.

Cases

Case 1

A 22-year old active male marine presented himself for care after experiencing exercise intolerance for over 4 months. This was preventing him from completing a standard 3 mile run as part of a general fitness test. He reported shortness of breath and fatigue while participating in minimal physical activity. Despite previously taking numerous medications the symptoms did not cease.

After numerous medical examinations the marine was found to have moderate restrictive lung disease, reduced lung capacity and moderate asthma with air trapping.

Treatment was conducted including a diagnostic and staging work-up with bone marrow biopsy and CT of the abdomen. He was also put through chemotherapy with doxorubicin, bleomycin, vinblastine and darcabazine. The treatment estimated a 90% recovery rate. He is expected to return to physical activity and his duties after completion of the chemotherapy.

Case 2

the case involved a female of 27 years who had a lifelong severe exercise intolerance manifested by muscle fatigue, lactic acidosis, and prominent symptoms of dyspnea and tachycardia. all of which were induced by minimal exercise. She was found to have a skeletal muscle respiratory chain defect characterized by low levels of cytochromes

An Investigation of the pathophysiology the women's exercise response revealed low maximal oxygen uptake (1/3 compared to a normal sedentary women). The findings also showed that impaired oxidative phosphorylation in working muscle disrupted the normal regulation of cardiac output and ventilation rate during exercise.[9]

References

  1. ^ Van de Weert-van Leeuwen, Pauline (2013). "Infection, inflammation and exercise in cystic fibrosis". Bio Med Central. doi:10.1186/1465-9921-14-32. Retrieved 13/04/2015. {{cite journal}}: Check date values in: |access-date= (help)CS1 maint: unflagged free DOI (link)
  2. ^ Brum, Marisa (2014). "Motor Neuron Syndrome as a New Phenotypic Manifestation of Mutation 9185T>C in Gene MTATP6". Case Rep Neurol Med. doi:10.1155/2014/701761. Retrieved 13/04/2015. {{cite journal}}: Check date values in: |access-date= (help)CS1 maint: unflagged free DOI (link)
  3. ^ Leonard, Jason (1/01/2014). "Predictors of post-infectious chronic fatigue syndrome in adolescents". Health Psychology and Behavioural Medicine. doi:10.1080/21642850.2013.869176. Retrieved 14/04/2015. {{cite journal}}: Check date values in: |access-date= and |date= (help)
  4. ^ Kozlowski, Karl F. (2013). "Exercise Intolerance in Individuals With Postconcussion Syndrome". Journal of athletic training. doi:10.4085/1062-6050-48.5.02. Retrieved 14/04/2015. {{cite journal}}: Check date values in: |access-date= (help)
  5. ^ Kozlowski, Karl F; Graham, James (2013). "Exercise Intolerance in Individuals With Postconcussion Syndrome". Journal of Athletic Training. 48 (5). National Athletic Trainers Association: 627–635. doi:10.4085/1062-6050-48.5.02.
  6. ^ Fowler, Robin (2012). "Exercise Intolerance in Pulmonary Arterial Hypertension". Pulmonary Medicine. doi:10.1155/2012/359204. Retrieved 13/04/2015. {{cite journal}}: Check date values in: |access-date= (help)CS1 maint: unflagged free DOI (link)
  7. ^ Geva, Professor Tal (2014). "Atrial septal defects". The Lancet. doi:10.1016/S0140-6736(13)62145-5. Retrieved 13/04/2015. {{cite journal}}: Check date values in: |access-date= (help)
  8. ^ Barel, Ortal (2008). "Mitochondrial Complex III Deficiency Associated with a Homozygous Mutation in UQCRQ". the American Journal Of Human Genetics. doi:10.1016/j.ajhg.2008.03.020. Retrieved 14/04/2014. {{cite journal}}: Check date values in: |access-date= (help)
  9. ^ a b Haller, R.G (1989). "Exercise intolerance, lactic acidosis, and abnormal cardiopulmonary regulation in exercise associated with adult skeletal muscle cytochrome c oxidase deficiency". the journal of clinical investigation. doi:10.1172/JCI114135. Retrieved 14/04/2015. {{cite journal}}: Check date values in: |access-date= (help)
  10. ^ Jones, Lee W; Eves, Neil D. "Exercise intolerance in cancer and the role of exercise therapy to reverse dysfunction". linkinghub.elsevier.com. Retrieved 2015-04-13.
  11. ^ Kitzman, Delane W (2005). "Exercise Intolerance". Progress in Cardiovascular Diseases. 47 (6): 367–379. doi:10.1016/j.pcad.2005.02.002.
  12. ^ Casaburi, R (2006). "Combination therapy for exercise intolerance in COPD". Thorax. 61 (7): 551–552. doi:10.1136/thx.2006.058511.

[1]

[2]

  1. ^ Walters, Dammann, Lynch, Katrina, Gregory, James (2005). "Exercise Intolerance in a Soldier Athlete". Medicine & Science in Sports & Exercise.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Massie, Wong, Milone, Rami, Lee-Jun, Margherita (2010). "Exercise intolerance due to cytochrome b mutation". Muscle & Nerve. doi:10.1002/mus.21649.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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