Exercise intolerance

Exercise intolerance
EKG of a 70-year-old man with exercise intolerance
Classification and external resources
ICD-10	R68.89
ICD-9-CM	V47.2

Exercise intolerance is a condition of inability or decreased ability to perform physical exercise at the expected level or duration of someone with a specific physical condition. It also includes experiences of 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 primary symptom of chronic diastolic heart failure.^[1]

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. Dysfunctions involving the pulmonary, cardiovascular or neuromuscular systems have been frequently found to be associated with exercise intolerance, with behavioural causes also playing a part in it.^[2]

Causes

Cardiorespiratory disorders

1. Cystic fibrosis; 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.^[3]
2. Bronchiectasis;
3. Spinal muscular atrophy; symptoms include exercise intolerance, cognitive impairment and fatigue.^[4]

Chronic fatigue syndrome

• Orthostatic intolerance (OI) occurs in CFS. OI 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.^[5]

Post-concussion syndrome

• Exercise intolerance is present in those with PCS however their intolerance to exercise may reduce over time.^[6]
• Individuals with postconcussion syndrome may also experience a level of exercise intolerance, however there is little known comparatively about exercise intolerance in PCS patients.^[7]

Rhabdomyolysis

Heart conditions

1. Cardiac arrhythmia;
2. Aortic valve insufficiency;
3. Pulmonary artery hypertension; PAH has the following symptoms; dyspnea and fatigue, these systems consequently contribute to exercise intolerance.^[8]
4. Asymptomatic atrial septal defects; 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.^[9]
5. Chronic heart failure

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.^[10]
2. a complex of Coenzyme 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.^[11]

• 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.^[12]

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.

Intracranial Hypertension - Individuals with elevated levels of cerebrospinal fluid can experience increased head pain, throbbing, pulsatile tinnitus, nausea and vomiting, faintness and weakness and even loss of consciousness after exercise or exertion.

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.

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 such as verapamil, enalapril, angiotensin receptor antagonism, and aldosterone antagonism could potentially improve exercise tolerance in these individuals as well.^[13]

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.^[14]

Hazards

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

• Decompensated heart failure
• Recent myocardial infarction
• Hypertrophic cardiomyopathy or cardiomyopathy from recent myocarditis
• Active or suspected myocarditis or pericarditis
• Low left ventricular ejection fraction
• Severe aortic stenosis
• Unstable ischemia
• Unstable arrythmia
• Irregular or resting pulse greater than 100 bpm
• Resting systolic blood pressure >200 mm Hg or resting diastolic blood pressure >110 mm Hg
• Severe pulmonary hypertension
• Severe chronic fatigue syndrome
• Suspected or known dissecting aneurysm
• Recent systemic or pulmonary embolus
• Pneumothorax and haemoptysis
• thrombophlebitis

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.

References

1. Dalane W. Kitzman, Leanne Groban (2011). "Exercise Intolerance". National Center for Biotechnology Information. Cardiol Clin. Retrieved 2015-04-17.
2. Scott Owens, Bernard Gutin (2000). "Exercise Intolerance". Pediatrics in Review. Retrieved 2015-04-17.
3. Van de Weert-van Leeuwen, Pauline (2013). "Infection, inflammation and exercise in cystic fibrosis". Bio Med Central. 14: 32. doi:10.1186/1465-9921-14-32. PMC 3599254. PMID 23497303.
4. Brum, Marisa (2014). "Motor Neuron Syndrome as a New Phenotypic Manifestation of Mutation 9185T>C in Gene MTATP6". Case Rep Neurol Med. 2014: 1–4. doi:10.1155/2014/701761. Retrieved 2015-04-13.
5. Leonard, Jason (2014-01-01). "Predictors of post-infectious chronic fatigue syndrome in adolescents". Health Psychology and Behavioural Medicine. 2: 41–51. doi:10.1080/21642850.2013.869176. PMC 3956649. PMID 24660116.
6. Kozlowski, Karl F. (2013). "Exercise Intolerance in Individuals With Postconcussion Syndrome". Journal of athletic training. 48: 627–35. doi:10.4085/1062-6050-48.5.02. PMC 3784364. PMID 23952041.
7. Kozlowski, Karl F; Graham, James (2013). "Exercise Intolerance in Individuals With Postconcussion Syndrome". Journal of Athletic Training. National Athletic Trainers Association. 48 (5): 627–635. doi:10.4085/1062-6050-48.5.02. PMC 3784364. PMID 23952041.
8. Fowler, Robin (2012). "Exercise Intolerance in Pulmonary Arterial Hypertension". Pulmonary Medicine. 2012: 359204. doi:10.1155/2012/359204. PMC 3377355. PMID 22737582.
9. Geva, Professor Tal (2014). "Atrial septal defects". The Lancet. 383: 1921–1932. doi:10.1016/S0140-6736(13)62145-5. Retrieved 2015-04-13.
10. Barel, Ortal (2008). "Mitochondrial Complex III Deficiency Associated with a Homozygous Mutation in UQCRQ". The American Journal of Human Genetics. 82: 1211–6. doi:10.1016/j.ajhg.2008.03.020. PMC 2427202. PMID 18439546.
11. 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. 84: 155–61. doi:10.1172/JCI114135. PMC 303965. PMID 2544623.
12. Jones, Lee W; Eves, Neil D. "Exercise intolerance in cancer and the role of exercise therapy to reverse dysfunction". linkinghub.elsevier.com. 10: 598–605. doi:10.1016/S1470-2045(09)70031-2. Retrieved 2015-04-13.
13. Kitzman, Delane W (2005). "Exercise Intolerance". Progress in Cardiovascular Diseases. 47 (6): 367–379. doi:10.1016/j.pcad.2005.02.002.
14. Casaburi, R (2006). "Combination therapy for exercise intolerance in COPD". Thorax. 61 (7): 551–552. doi:10.1136/thx.2006.058511.

Walters, Dammann, Lynch, Katrina, Gregory, James (2005). "Exercise intolerance in a soldier athlete". Medicine & Science in Sports & Exercise. 37: S131–S132. doi:10.1097/00005768-200505001-00685.

Massie, Wong, Milone, Rami, Lee-Jun, Margherita (2010). "Exercise intolerance due to cytochrome b mutation". Muscle & Nerve. 42: 136–140. doi:10.1002/mus.21649.

Quinlivan, Jungbluth, Ros, Heinz (2012). "Myopathic causes of exercise intolerance with rhabdomyolysis". Developmental Medicine & Child Neurology. 54: 886–891. doi:10.1111/j.1469-8749.2012.04320.x.

Kitzman, Dalane W (2005). "Exercise intolerance". Progress In Cardiovascular Diseases. 47: 367–379. doi:10.1016/j.pcad.2005.02.002.