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Swallowing problems for liquids and solids/Achalasia is a rare neurodegenerative motor smooth muscle motility disorder of the esophagus resulting in deranged oesophageal peristalsis and loss of lower oesophageal sphincter function that makes it difficult for food and liquid to pass into your stomach. Achalasia occurs when nerves in the tube connecting your mouth and stomach (esophagus) become damaged. As a result, the esophagus loses the ability to squeeze food down, and the muscular valve between the esophagus and stomach (lower esophageal sphincter) doesn’t fully relax — making it difficult for food to pass into your stomach.

Achalasia is a rare disorder that makes it difficult for food and liquid to pass from the swallowing tube connecting your mouth and stomach (esophagus) into your stomach.

Synonyms of Achalasia

• Cardiospasm
• Dyssynergia esophagus
• Esophageal peristalsis
• Megaesophagus
• Esophageal achalasia;
• Swallowing problems for liquids and solids;
• lower esophageal sphincter spasm

Types of Achalasia

Causes of Achalasia

Dysphagia could be during the oropharyngeal or pharyngeal phases of swallowing.

A. Oropharyngeal dysphagia

It is a delay in the transit of liquid or solid bolus during the oropharyngeal phase of swallowing. It could be due to three main subgroups – (1) neurological, (2) muscular, or (3) anatomical.[rx]

• Neurological causes include cerebrovascular accidents (post-stroke dysphagia), brainstem infarctions with cranial nerve involvement. Other causes include basal ganglia lesions as in Parkinson’s disease. Also, head and neck injuries and surgery, multiple sclerosis, central nervous tumor, botulism, amyotrophic lateral sclerosis, supranuclear palsy, and degenerative cervical spine disease.
• Muscular causes include polymyositis, muscular dystrophy, and myasthenia gravis (a lesion at the neuromuscular junction).
• Anatomical causes include Zenker diverticulum, enlarged thyroid, esophageal web, tumors, abscess, external compression by an aortic aneurysm (known as dysphagia aortic).[rx] Also, cervical discectomy and fusion may be associated with postoperative dysphagia.[rx][rx]

B. Esophageal dysphagia- could be due to mechanical obstruction, or motility disorders. 

• Mechanical obstruction causes include Schatzki ring, esophageal stricture, esophageal carcinoma, eosinophilic esophagitis.[rx]
• Motility disorder causes include esophageal spasm, achalasia, ineffective esophageal motility, and scleroderma.

Mechanical obstruction is associated with dysphagia only to solid food, while the motility disorder causes are usually associated with solid and liquid dysphagia. The dysphagia may be intermittent (e.g., Schatzki ring, esophageal spasm) or permanent (as in esophageal stricture, carcinoma, achalasia, scleroderma, ineffective esophageal motility).[rx]

C. Rheumatological disorders

• Sjogren syndrome (occurs in one-third of patients and caused by both xerostomia and abnormal esophageal motility, mainly of the proximal esophagus.
• Systemic lupus erythematosus
• Mixed connective tissue disease
• Rheumatoid arthritis.
• Systemic sclerosis (as part of the CREST syndrome)

D. Medications

Several drugs may contribute to the severity of dysphagia. The mechanisms by which these drugs may cause dysphagia include xerostomia and changes in esophageal motility. Also, the dysphagia may be secondary to the development of drug-induced esophagitis or the development of gastroesophageal reflux disease. Examples of these drugs are:

• Antipsychotic (e.g., olanzapine, clozapine)
• Tricyclic antidepressant
• Potassium supplements
• NSAIDs
• Bisphosphonates
• Calcium channel blockers
• Nitrates
• Theophylline
• Alcohol
• Medications with immunosuppressant effects (e.g., cyclosporin) can predispose to infective esophagitis and dysphagia
• Opioids[7]

It is important to note here that narcotic sedatives such as opioids can lead to compromise of airway due to central effects and could increase the risk of aspiration in patients with dysphagia. The use of opiates, even in low disease, in patients with psychiatric disorders or Parkinson’s disease, can develop hypercontractile or hypertensive esophageal consequences mimicking type III achalasia.

Others

• Diffuse esophageal spasm.
• Esophageal cancer.
• Eosinophilic esophagitis[rx]
• Hiatal hernia.
• Parkinson disease.
• Zenker diverticulum.
• Multiple sclerosis.
• Paterson-Kelly syndrome.
• Dysphagia lusoria is a type of dysphagia that develops in childhood, due to compression of the esophagus by vascular abnormality. Usually, there is an aberrant right subclavian artery arising from the left side of the aortic arch, or a double aortic arch, or other rare anomalies.
• Benign strictures.
• Esophageal webs and rings
• Esophageal reflux[rx]

Symptoms of Achalasia

Achalasia symptoms generally appear gradually and worsen over time. Signs and symptoms may include:

• Inability to swallow (dysphagia), which may feel like food or drink is stuck in your throat
• Regurgitating food or saliva
• Heartburn
• Belching
• Chest pain that comes and goes
• Coughing at night
• Pneumonia (from aspiration of food into the lungs)
• Weight loss
• Vomiting
• Trouble swallowing (dysphagia). This is the most common early symptom.
• Regurgitation of undigested food.
• Chest pain that comes and goes; pain can be severe.
• Cough at night
• Weight loss/malnutrition from difficulty eating. This is a late symptom.
• Hiccups, difficulty belching (less common symptoms)

Diagnosis of Achalasia

Achalasia can be overlooked or misdiagnosed because it has symptoms similar to other digestive disorders. To test for achalasia, your doctor is likely to recommend:

• Endoscopy – Approximately 2% to 4% of patients with suspected achalasia have pseudoachalasia from infiltrating malignancy or stricture.^[rx] Potential risk factors for malignancy-associated pseudoachalasia include older age at the time of diagnosis, shorter duration of symptoms, and more weight loss (12 vs 5 kg) on presentation.^[rx] Patients with 2 or more of these risk factors on presentation should undergo a careful investigation to rule out malignancy.^[rx,rx]
• Barium esophagram – A barium esophagram is a noninvasive radiologic study that can assist with initial diagnosis or response to treatment with graded PD. A barium swallow evaluates the morphology of the esophagus and classically shows a dilated or tortuous esophagus with a narrowed LES and “bird’s beak” appearance.
• Manometry – HRM is the gold standard test for the diagnosis of achalasia. Conventional manometry tracings in patients with achalasia show the absence of esophageal peristalsis and incomplete LES relaxation with residual pressures of over 10 mm Hg. HRM with esophageal pressure topography is more sensitive and specific than conventional manometry and is able to classify achalasia into 3 distinct subtypes, which can have treatment implications.^[rx] Type II achalasia has the best response to treatment, followed by type I achalasia, whereas type III achalasia is the most difficult to treat.^[rx,rx]
• Esophageal manometry. This test measures the rhythmic muscle contractions in your esophagus when you swallow, the coordination and force exerted by the esophagus muscles, and how well your lower esophageal sphincter relaxes or opens during a swallow. This test is the most helpful when determining which type of motility problem you might have.
• X-rays of your upper digestive system (esophagram). X-rays are taken after you drink a chalky liquid that coats and fills the inside lining of your digestive tract. The coating allows your doctor to see a silhouette of your esophagus, stomach, and upper intestine. You may also be asked to swallow a barium pill that can help to show a blockage of the esophagus.
• Upper endoscopy. Your doctor inserts a thin, flexible tube equipped with a light and camera (endoscope) down your throat, to examine the inside of your esophagus and stomach. Endoscopy can be used to define a partial blockage of the esophagus if your symptoms or results of a barium study indicate that possibility. Endoscopy can also be used to collect a sample of tissue (biopsy) to be tested for complications of reflux such as Barrett’s esophagus.

Treatment of Achalasia

Achalasia treatment focuses on relaxing or stretching open the lower esophageal sphincter so that food and liquid can move more easily through your digestive tract.

Specific treatment depends on your age, health condition and the severity of the achalasia.

Nonsurgical treatment

Nonsurgical options include:

• The management plan. may include (i) elimination of certain food consistencies from the diet. (ii) adjustment of meal bolus seizes and (iii) use of techniques such as chin-tuck, head-turn, and supraglottic maneuvers to help in minimizing/preventing aspiration. Also, strengthening and coordinating muscles involved in swallowing. Gastroscopy tubes may be indicated in patients who fail to respond to the above-stated measures.[rx]
• Pneumatic dilation. A balloon is inserted by endoscopy into the center of the esophageal sphincter and inflated to enlarge the opening. This outpatient procedure may need to be repeated if the esophageal sphincter doesn’t stay open. Nearly one-third of people treated with balloon dilation need repeat treatment within five years. This procedure requires sedation.
• Botox (botulinum toxin type A). This muscle relaxant can be injected directly into the esophageal sphincter with an endoscopic needle. The injections may need to be repeated, and repeat injections may make it more difficult to perform surgery later if needed. Botox is generally recommended only for people who aren’t good candidates for pneumatic dilation or surgery due to age or overall health. Botox injections typically do not last more than six months. A strong improvement from the injection of Botox may help confirm a diagnosis of achalasia.
• BT injection. for achalasia is an effective short-term therapy. BT injection into the LES locally inhibits the release of acetylcholine, causing relaxation of the smooth muscle, which allows for easier passage of food bolus into the gastric body.
• Balloon dilation. In this non-surgical procedure, you’ll be put under light sedation while a specifically designed balloon is inserted through the LES and then inflated. The procedure relaxes the muscle sphincter, which allows food to enter your stomach. Balloon dilation is usually the first treatment option in people in whom surgery fails. You may have to undergo several dilation treatments to relieve your symptoms, and every few years to maintain relief.
• Stretching the esophagus (pneumatic dilation). The doctor inserts a balloon in the valve between the esophagus and stomach and blows it up to stretch the tight muscles. You might need this procedure several times before it helps.

Medication

• Muscle relaxants – such as nitroglycerin (Nitrostat) or nifedipine (Procardia) before eating. These medications have limited treatment effects and severe side effects. Medications are generally considered only if you’re not a candidate for pneumatic dilation or surgery, and Botox hasn’t helped. This type of therapy is rarely indicated.
• Sublingual nifedipine – significantly improves outcomes in 75% of people with mild or moderate disease. It was classically considered that surgical myotomy provided greater benefit than either botulinum toxin or dilation in those who fail medical management.^[rx] However, a recent randomized controlled trial found pneumatic dilation to be non-inferior to laparoscopic Heller myotomy.^[rx]
• Pharmacotherapy-nitrates, calcium-channel blockers – (e.g., nifedipine 10 to 20 mg sublingual 15 to 30 minutes before meals). It acts by lowering the lower esophageal sphincter resting pressure. Nitrates, calcium channel blockers, and phosphodiesterase-5 inhibitors to reduce the lower esophageal sphincter (LES) pressure.
• Calcium channel blockers  – inhibit the entry of calcium into the cells blocking smooth muscle contraction, leading to a decrease in LES pressure. Hypotension, pedal edema, headache, the rapid development of tolerance, and incomplete symptom improvement are limiting factors to its use. Nitrates increase nitric oxide concentrations in smooth muscles, causing an increase in cyclic adenosine monophosphate levels, which leads to smooth muscle relaxation. These treatments are less effective, provide only short-term relief of symptoms, and are primarily reserved for patients who are waiting for or who refused more definitive therapy, such as pneumatic dilatation or surgery.[rx][rx]
• Scopolamine – also known as hyoscine Devil’s Breath, is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is formally used as a medication for treating motion and sickness, achalasia, and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva.^[rx] When used by injection, effects begin after about 20 minutes and last for up to 8 hours.^[rx] It may also be used orally and as a transdermal patch.^[rx]

Surgery

Surgical options for treating achalasia include:

• Peroral endoscopic myotomy (POEM) – is an effective minimally invasive alternative to laparoscopic Heller myotomy to treat achalasia at limited centers.[rx] Dissection of the circular fibers of the LES is achieved endoscopically, leading to relaxation of the LES; however, the risk of gastroesophageal reflux is high because it does not include an antireflux procedure. Esophagectomy is the last resort.
• Heller myotomy. The surgeon cuts the muscle at the lower end of the esophageal sphincter to allow food to pass more easily into the stomach. The procedure can be done noninvasively (laparoscopic Heller myotomy). Some people who have a Heller myotomy may later develop gastroesophageal reflux disease (GERD). To avoid future problems with GERD, a procedure known as fundoplication might be performed at the same time as a Heller myotomy. In fundoplication, the surgeon wraps the top of your stomach around the lower esophagus to create an anti-reflux valve, preventing acid from coming back (GERD) into the esophagus. Fundoplication is usually done with a minimally invasive (laparoscopic) procedure.
• Peroral endoscopic myotomy (POEM). In the POEM procedure, the surgeon uses an endoscope inserted through your mouth and down your throat to create an incision in the inside lining of your esophagus. Then, as in a Heller myotomy, the surgeon cuts the muscle at the lower end of the esophageal sphincter. POEM may also be combined with or followed by later fundoplication to help prevent GERD. Some patients who have a POEM and develop GERD after the procedure are treated with daily oral medication.

References

People Also Reading

Lower Esophageal Sphincter Spasm – Symptoms, Treatment Esophageal Peristalsis – Causes, Symptoms, Treatment Achalasia – Causes, Symptoms, Diagnosis, Treatment Esophageal Achalasia – Causes, Symptoms, Treatment Cardiospasm – Causes, Symptoms, Diagnosis, Treatment Achalasia – Causes, Symptoms, Diagnosis, Treatment Esophageal Achalasia – Causes, Symptoms, Treatment Stomach Problems – Causes, Symptoms, Diagnosis, Treatment Acid Regurgitation – Causes, Symptoms, Treatment Regurgitation – Causes, Symptoms, Diagnosis, Treatment Gastrointestinal Liver Pancreatic Diseases List Can itchy skin be a sign of liver problems?

Lower Esophageal Sphincter Spasm/Achalasia is a rare neurodegenerative motor smooth muscle motility disorder of the esophagus resulting in deranged oesophageal peristalsis and loss of lower oesophageal sphincter function that makes it difficult for food and liquid to pass into your stomach. Achalasia occurs when nerves in the tube connecting your mouth and stomach (esophagus) become damaged. As a result, the esophagus loses the ability to squeeze food down, and the muscular valve between the esophagus and stomach (lower esophageal sphincter) doesn’t fully relax — making it difficult for food to pass into your stomach.

Achalasia is a rare disorder that makes it difficult for food and liquid to pass from the swallowing tube connecting your mouth and stomach (esophagus) into your stomach.

Synonyms of Achalasia

• Cardiospasm
• Dyssynergia esophagus
• Esophageal peristalsis
• Megaesophagus
• Esophageal achalasia;
• Swallowing problems for liquids and solids;
• lower esophageal sphincter spasm

Types of Achalasia

Causes of Achalasia

Dysphagia could be during the oropharyngeal or pharyngeal phases of swallowing.

A. Oropharyngeal dysphagia

It is a delay in the transit of liquid or solid bolus during the oropharyngeal phase of swallowing. It could be due to three main subgroups – (1) neurological, (2) muscular, or (3) anatomical.[rx]

• Neurological causes include cerebrovascular accidents (post-stroke dysphagia), brainstem infarctions with cranial nerve involvement. Other causes include basal ganglia lesions as in Parkinson’s disease. Also, head and neck injuries and surgery, multiple sclerosis, central nervous tumor, botulism, amyotrophic lateral sclerosis, supranuclear palsy, and degenerative cervical spine disease.
• Muscular causes include polymyositis, muscular dystrophy, and myasthenia gravis (a lesion at the neuromuscular junction).
• Anatomical causes include Zenker diverticulum, enlarged thyroid, esophageal web, tumors, abscess, external compression by an aortic aneurysm (known as dysphagia aortic).[rx] Also, cervical discectomy and fusion may be associated with postoperative dysphagia.[rx][rx]

B. Esophageal dysphagia- could be due to mechanical obstruction, or motility disorders. 

• Mechanical obstruction causes include Schatzki ring, esophageal stricture, esophageal carcinoma, eosinophilic esophagitis.[rx]
• Motility disorder causes include esophageal spasm, achalasia, ineffective esophageal motility, and scleroderma.

Mechanical obstruction is associated with dysphagia only to solid food, while the motility disorder causes are usually associated with solid and liquid dysphagia. The dysphagia may be intermittent (e.g., Schatzki ring, esophageal spasm) or permanent (as in esophageal stricture, carcinoma, achalasia, scleroderma, ineffective esophageal motility).[rx]

C. Rheumatological disorders

• Sjogren syndrome (occurs in one-third of patients and caused by both xerostomia and abnormal esophageal motility, mainly of the proximal esophagus.
• Systemic lupus erythematosus
• Mixed connective tissue disease
• Rheumatoid arthritis.
• Systemic sclerosis (as part of the CREST syndrome)

D. Medications

Several drugs may contribute to the severity of dysphagia. The mechanisms by which these drugs may cause dysphagia include xerostomia and changes in esophageal motility. Also, the dysphagia may be secondary to the development of drug-induced esophagitis or the development of gastroesophageal reflux disease. Examples of these drugs are:

• Antipsychotic (e.g., olanzapine, clozapine)
• Tricyclic antidepressant
• Potassium supplements
• NSAIDs
• Bisphosphonates
• Calcium channel blockers
• Nitrates
• Theophylline
• Alcohol
• Medications with immunosuppressant effects (e.g., cyclosporin) can predispose to infective esophagitis and dysphagia
• Opioids[7]

It is important to note here that narcotic sedatives such as opioids can lead to compromise of airway due to central effects and could increase the risk of aspiration in patients with dysphagia. The use of opiates, even in low disease, in patients with psychiatric disorders or Parkinson’s disease, can develop hypercontractile or hypertensive esophageal consequences mimicking type III achalasia.

Others

• Diffuse esophageal spasm.
• Esophageal cancer.
• Eosinophilic esophagitis[rx]
• Hiatal hernia.
• Parkinson disease.
• Zenker diverticulum.
• Multiple sclerosis.
• Paterson-Kelly syndrome.
• Dysphagia lusoria is a type of dysphagia that develops in childhood, due to compression of the esophagus by vascular abnormality. Usually, there is an aberrant right subclavian artery arising from the left side of the aortic arch, or a double aortic arch, or other rare anomalies.
• Benign strictures.
• Esophageal webs and rings
• Esophageal reflux[rx]

Symptoms of Achalasia

Achalasia symptoms generally appear gradually and worsen over time. Signs and symptoms may include:

• Inability to swallow (dysphagia), which may feel like food or drink is stuck in your throat
• Regurgitating food or saliva
• Heartburn
• Belching
• Chest pain that comes and goes
• Coughing at night
• Pneumonia (from aspiration of food into the lungs)
• Weight loss
• Vomiting
• Trouble swallowing (dysphagia). This is the most common early symptom.
• Regurgitation of undigested food.
• Chest pain that comes and goes; pain can be severe.
• Cough at night
• Weight loss/malnutrition from difficulty eating. This is a late symptom.
• Hiccups, difficulty belching (less common symptoms)

Diagnosis of Achalasia

Achalasia can be overlooked or misdiagnosed because it has symptoms similar to other digestive disorders. To test for achalasia, your doctor is likely to recommend:

• Endoscopy – Approximately 2% to 4% of patients with suspected achalasia have pseudoachalasia from infiltrating malignancy or stricture.³⁶ Potential risk factors for malignancy-associated pseudoachalasia include older age at the time of diagnosis, shorter duration of symptoms, and more weight loss (12 vs 5 kg) on presentation.³⁷ Patients with 2 or more of these risk factors on presentation should undergo a careful investigation to rule out malignancy.^36,37
• Barium esophagram – A barium esophagram is a noninvasive radiologic study that can assist with initial diagnosis or response to treatment with graded PD. A barium swallow evaluates the morphology of the esophagus and classically shows a dilated or tortuous esophagus with a narrowed LES and “bird’s beak” appearance (Figure 5).
• Manometry – HRM is the gold standard test for the diagnosis of achalasia. Conventional manometry tracings in patients with achalasia show the absence of esophageal peristalsis and incomplete LES relaxation with residual pressures of over 10 mm Hg. HRM with esophageal pressure topography is more sensitive and specific than conventional manometry and is able to classify achalasia into 3 distinct subtypes, which can have treatment implications (Table 3).⁷ Type II achalasia has the best response to treatment, followed by type I achalasia, whereas type III achalasia is the most difficult to treat.^41,42
• Esophageal manometry. This test measures the rhythmic muscle contractions in your esophagus when you swallow, the coordination and force exerted by the esophagus muscles, and how well your lower esophageal sphincter relaxes or opens during a swallow. This test is the most helpful when determining which type of motility problem you might have.
• X-rays of your upper digestive system (esophagram). X-rays are taken after you drink a chalky liquid that coats and fills the inside lining of your digestive tract. The coating allows your doctor to see a silhouette of your esophagus, stomach, and upper intestine. You may also be asked to swallow a barium pill that can help to show a blockage of the esophagus.
• Upper endoscopy. Your doctor inserts a thin, flexible tube equipped with a light and camera (endoscope) down your throat, to examine the inside of your esophagus and stomach. Endoscopy can be used to define a partial blockage of the esophagus if your symptoms or results of a barium study indicate that possibility. Endoscopy can also be used to collect a sample of tissue (biopsy) to be tested for complications of reflux such as Barrett’s esophagus.

Treatment of Achalasia

Achalasia treatment focuses on relaxing or stretching open the lower esophageal sphincter so that food and liquid can move more easily through your digestive tract.

Specific treatment depends on your age, health condition and the severity of the achalasia.

Nonsurgical treatment

Nonsurgical options include:

• The management plan. may include (i) elimination of certain food consistencies from the diet. (ii) adjustment of meal bolus seizes and (iii) use of techniques such as chin-tuck, head-turn, and supraglottic maneuvers to help in minimizing/preventing aspiration. Also, strengthening and coordinating muscles involved in swallowing. Gastroscopy tubes may be indicated in patients who fail to respond to the above-stated measures.[1]
• Pneumatic dilation. A balloon is inserted by endoscopy into the center of the esophageal sphincter and inflated to enlarge the opening. This outpatient procedure may need to be repeated if the esophageal sphincter doesn’t stay open. Nearly one-third of people treated with balloon dilation need repeat treatment within five years. This procedure requires sedation.
• Botox (botulinum toxin type A). This muscle relaxant can be injected directly into the esophageal sphincter with an endoscopic needle. The injections may need to be repeated, and repeat injections may make it more difficult to perform surgery later if needed. Botox is generally recommended only for people who aren’t good candidates for pneumatic dilation or surgery due to age or overall health. Botox injections typically do not last more than six months. A strong improvement from the injection of Botox may help confirm a diagnosis of achalasia.
• BT injection. for achalasia is an effective short-term therapy. BT injection into the LES locally inhibits the release of acetylcholine, causing relaxation of the smooth muscle, which allows for easier passage of food bolus into the gastric body.
• Balloon dilation. In this non-surgical procedure, you’ll be put under light sedation while a specifically designed balloon is inserted through the LES and then inflated. The procedure relaxes the muscle sphincter, which allows food to enter your stomach. Balloon dilation is usually the first treatment option in people in whom surgery fails. You may have to undergo several dilation treatments to relieve your symptoms, and every few years to maintain relief.
• Stretching the esophagus (pneumatic dilation). The doctor inserts a balloon in the valve between the esophagus and stomach and blows it up to stretch the tight muscles. You might need this procedure several times before it helps.

Medication.

• Muscle relaxants – such as nitroglycerin (Nitrostat) or nifedipine (Procardia) before eating. These medications have limited treatment effects and severe side effects. Medications are generally considered only if you’re not a candidate for pneumatic dilation or surgery, and Botox hasn’t helped. This type of therapy is rarely indicated.
• Sublingual nifedipine – significantly improves outcomes in 75% of people with mild or moderate disease. It was classically considered that surgical myotomy provided greater benefit than either botulinum toxin or dilation in those who fail medical management.^[rx] However, a recent randomized controlled trial found pneumatic dilation to be non-inferior to laparoscopic Heller myotomy.^[rx]
• Pharmacotherapy-nitrates, calcium-channel blockers – (e.g., nifedipine 10 to 20 mg sublingual 15 to 30 minutes before meals). It acts by lowering the lower esophageal sphincter resting pressure. Nitrates, calcium channel blockers, and phosphodiesterase-5 inhibitors to reduce the lower esophageal sphincter (LES) pressure.
• Calcium channel blockers  – inhibit the entry of calcium into the cells blocking smooth muscle contraction, leading to a decrease in LES pressure. Hypotension, pedal edema, headache, the rapid development of tolerance, and incomplete symptom improvement are limiting factors to its use. Nitrates increase nitric oxide concentrations in smooth muscles, causing an increase in cyclic adenosine monophosphate levels, which leads to smooth muscle relaxation. These treatments are less effective, provide only short-term relief of symptoms, and are primarily reserved for patients who are waiting for or who refused more definitive therapy, such as pneumatic dilatation or surgery.[rx][rx]
• Scopolamine – also known as hyoscine Devil’s Breath, is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is formally used as a medication for treating motion and sickness, achalasia, and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva.^[rx] When used by injection, effects begin after about 20 minutes and last for up to 8 hours.^[rx] It may also be used orally and as a transdermal patch.^[rx]

Surgery

Surgical options for treating achalasia include:

• Peroral endoscopic myotomy (POEM) – is an effective minimally invasive alternative to laparoscopic Heller myotomy to treat achalasia at limited centers.[rx] Dissection of the circular fibers of the LES is achieved endoscopically, leading to relaxation of the LES; however, the risk of gastroesophageal reflux is high because it does not include an antireflux procedure. Esophagectomy is the last resort.
• Heller myotomy. The surgeon cuts the muscle at the lower end of the esophageal sphincter to allow food to pass more easily into the stomach. The procedure can be done noninvasively (laparoscopic Heller myotomy). Some people who have a Heller myotomy may later develop gastroesophageal reflux disease (GERD). To avoid future problems with GERD, a procedure known as fundoplication might be performed at the same time as a Heller myotomy. In fundoplication, the surgeon wraps the top of your stomach around the lower esophagus to create an anti-reflux valve, preventing acid from coming back (GERD) into the esophagus. Fundoplication is usually done with a minimally invasive (laparoscopic) procedure.
• Peroral endoscopic myotomy (POEM). In the POEM procedure, the surgeon uses an endoscope inserted through your mouth and down your throat to create an incision in the inside lining of your esophagus. Then, as in a Heller myotomy, the surgeon cuts the muscle at the lower end of the esophageal sphincter. POEM may also be combined with or followed by later fundoplication to help prevent GERD. Some patients who have a POEM and develop GERD after the procedure are treated with daily oral medication.

References

People Also Reading

Esophageal Peristalsis – Causes, Symptoms, Treatment Esophageal Achalasia – Causes, Symptoms, Treatment Esophageal Achalasia – Causes, Symptoms, Treatment Achalasia – Causes, Symptoms, Diagnosis, Treatment Cardiospasm – Causes, Symptoms, Diagnosis, Treatment Achalasia – Causes, Symptoms, Diagnosis, Treatment Swallowing problems for liquids and solids Acid Regurgitation – Causes, Symptoms, Treatment Regurgitation – Causes, Symptoms, Diagnosis, Treatment Hemifacial Spasm – Causes, Symptoms, Treatment Esophageal Thrush, Causes, Symptoms, Treatment Esophageal Candidiasis Symptoms, Treatment

Altitude-Related Disorders/Altitude sickness occurs when you cannot get enough oxygen from the air at high altitudes. This causes symptoms such as a headache, loss of appetite, and trouble sleeping. It happens most often when people who are not used to high altitudes go quickly from lower altitudes to 8000 ft (2500 m) or higher. For example, you may get a headache when you drive over a high mountain pass, hike to a high altitude, or arrive at a mountain resort.

Acute mountain sickness (AMS) is a syndrome that arises in non-acclimatized individuals who ascend to high altitudes. It is a form of acute altitude illness that occurs due to a decrease in the atmospheric partial pressure of oxygen as the altitude increases, inducing hypoxia. This includes acute mountain sickness (AMS), high-altitude cerebral oedema (HACE), and high-altitude pulmonary edema (HAPE).  This condition typically occurs at an altitude of >2500 meters; however, it can occur at lower elevations in high-risk individuals.[rx][rx]

Types of High Altitude Sickness

High altitude oxygenation is improving oxygenation or enriching the body with additional oxygen at high altitudes.[rx]

According to the Society of Mountain Medicine (Effects of high altitude on humans), there are three altitude regions:

• High Altitude  – 1500 to 3500 meters above sea level (4900-11500 ft.)
• Very high altitude – 3500 to 5500 meters above sea level (11500 to 18000 ft.)
• Extreme altitude –  above 5500 meters above sea level (18000 ft.)

Most people who get altitude sickness get AMS, acute mountain sickness. Higher than 10,000 feet, 75% of people will get mild symptoms. There are three categories of AMS:

• Mild AMS – Symptoms, such as mild headache and fatigue, don’t interfere with your normal activity. Symptoms improve after a few days as your body acclimates. You can likely stay at your current elevation as your body adjusts.
• Moderate AMS – Symptoms start to interfere with your activities. You may experience severe headaches, nausea, and difficulty with coordination. You’ll need to descend to start to feel better.
• Severe AMS – You may feel short of breath, even at rest. It can be difficult to walk. You need to descend immediately to a lower altitude and seek medical care.
• HAPE (High-altitude pulmonary edema) – HAPE produces excess fluid on the lungs, causing breathlessness, even when resting. You feel very fatigued and weak and may feel like you’re suffocating.
• HACE (High-altitude cerebral edema) – HACE involves excess fluid on the brain, causing brain swelling. You may experience confusion, lack of coordination, and possibly violent behavior.

Causes of Altitude-Related Disorders

Acute Mountain Sickness is caused by the body’s reaction to the reduced oxygen level in respired air and resultant tissue hypoxia. At baseline metabolic levels, the brain is the most sensitive organ regarding hypoxia and oxygen stress. Thus, the symptoms of Acute Mountain Sickness (discussed below) are mediated by the central nervous system (CNS). In many travelers at altitude, respirations during sleep develop a periodic pattern that may contribute to the development of symptoms.[rx][rx]

Along with other illnesses related to altitude, HAPE occurs above 2500 meters but can occur at altitudes as low as 2000 meters. Risk factors include individual susceptibility due to low hypoxic ventilatory response (HVR), the altitude attained, a rapid rate of ascent, male sex, use of sleep medication, excessive salt ingestion, ambient cold temperature, and heavy physical exertion. Preexisting conditions such as those leading to increased pulmonary blood flow, pulmonary hypertension, increased pulmonary vascular reactivity, or patent foramen ovale may have a higher predisposition towards the development of HAPE. [rx][rx][rx]

• Asthma
• Bronchitis
• Mucous plugging
• Myocardial infarction
• Pneumonia
• Pneumothorax
• Pulmonary embolism
• Upper respiratory tract infection
• Acute psychosis
• Brain tumour
• Carbon monoxide poisoning
• Central nervous system infection
• Cerebrovascular bleed or infarct
• Cerebrovascular spasm
• Diabetic ketoacidosis
• Hypoglycemia
• Hyponatremia
• Ingestion of drugs
• Seizure disorder
• Coronary artery bypass
• Eisenmenger syndrome
• Severe symptomatic valvular heart disease
• Severe decompensated congestive heart disease
• Uncontrolled ventricular and supraventricular tachycardia
• Uncontrolled hypertension
• Unstable angina
• History of altitude illness
• The rate of ascent
• The ultimate altitude reached
• Other medical conditions such as pulmonary hypertension, chronic obstructive pulmonary disease, restrictive lung disease, pulmonary fibrosis, and congenital heart disease
• The degree of cold
• The amount of physical exertion
• Use of alcohol and sleeping pills

Symptoms of Altitude-Related Disorders

Some symptoms of low oxygen saturation levels include:

• Shortness of breath
• Cyanosis
• Extreme fatigue and weakness
• Mental confusion
• Headaches

Treatments of Altitude-Related Disorders

Non-pharmacological

• Pure oxygen – Giving pure oxygen can help a person with severe breathing problems caused by altitude sickness. Physicians at mountain resorts commonly provide this treatment.
• A Gamow bag – This portable plastic hyperbaric chamber can be inflated with a foot pump and is used when a rapid descent is not possible. It can reduce the effective altitude by up to 5,000 ft (1,500 m). It is usually used as an aid to evacuate people with severe symptoms, not to treat them at high altitudes.
• Gradual Ascent – The recommended method for the prevention of high-altitude illness is to allow the body time to acclimatize via gradual ascent. The WMS recommends one day of travel for every 1,500 ft ascent above 10,000 ft above sea level and a day of rest every 3 to 4 days of travel.
• Descent – Non-severe AMS: Descent is not necessary for non-severe AMS. It responds well to rest and/or pharmacological treatment. If symptoms resolve, ascent may resume. Severe AMS is AMS with incapacitating symptoms. The appropriate and definitive treatment for severe AMS is immediate descent to a lower altitude.
• Supplemental Oxygen – If available, supplemental oxygen should be administered with oxygen saturation of above 90% as a goal for both severe AMS and HACE.  Supplemental oxygen should only be used in conjunction with evacuation or while waiting for it.
• Portable Hyperbaric Chamber – These portable chambers are indicated for severe AMS and HACE when evacuation is delayed.  Symptoms will recur when the patient exits the chamber. However, it may temporarily improve symptoms long enough for patients to be able to assist with their evacuation.  The equipment and constant supervision make this a resource-intensive treatment, but it has the potential to save lives in remote areas where evacuation may be delayed.

Medication

Established drug treatments include acetazolamide, dexamethasone, and nifedipine. Acetazolamide is thought to be effective in treating AMS, creating an acidemia, increasing ventilation, and therefore, increasing the arterial oxygen content.[rx] Dexamethasone is effective at reducing edema and symptoms in HACE, just as it is in any other form of cerebral edema. Nifedipine is used in HAPE for its dilatory effect on the pulmonary vasculature; however, a recent study did not demonstrate any benefit over descent and supplemental oxygen in patients with HAPE.[rx] In addition to these established treatments, potential novel therapies have been suggested such as ibuprofen, nitrates, and intravenous (IV) iron supplementation.

Acetazolamide

Acetazolamide prevents AMS when taken before ascent; it can also help speed recovery if taken after symptoms have developed. The drug works by acidifying the blood and reducing the respiratory alkalosis associated with high elevations, thus increasing respiration and arterial oxygenation and speeding acclimatization. An effective dose that minimizes the common side effects of increased urination and paresthesias of the fingers and toes is 125 mg every 12 hours, beginning the day before ascent and continuing the first 2 days at elevation, or longer if ascent continues.

Acetazolamide (125mg PO every 12 hours)

• Acetazolamide is the only medication proven to speed acclimatization. It induces metabolic acidosis by bicarbonate diuresis. This acidosis triggers compensatory hyperventilation helping acclimatization. There are two adverse effects of this medication worth considering.  First, acetazolamide increases urination frequency and therefore increases the risk of dehydration, which is a concern during high altitude travel[rx].  Secondly, acetazolamide has a similar molecular structure to sulfa medications and should be used cautiously in patients with sulfa allergy.  Although the risk of cross-reactivity is low, travelers with sulfa allergies are recommended to undergo a trial of acetazolamide before travel.[rx][rx]

Allergic reactions to acetazolamide are uncommon. As a nonantimicrobial sulfonamide, it does not cross-react with antimicrobial sulfonamides. However, it is best avoided by people with a history of anaphylaxis to any sulfa. People with a history of severe penicillin allergy have occasionally had allergic reactions to acetazolamide. The pediatric dose is 5 mg/kg/day in divided doses, up to 125 mg twice a day.

Dexamethasone

Dexamethasone (initial 8mg PO, IM, or IV followed in 6 hours by 4mg PO, IM, or IV every 6 hours). Dexamethasone is effective for preventing and treating AMS and HACE and prevents HAPE as well. Unlike acetazolamide, if the drug is discontinued at elevation before acclimatization, a mild rebound can occur. Acetazolamide is preferable to prevent AMS while ascending, with dexamethasone reserved as an adjunct treatment for the descent. The adult dose is 4 mg every 6 hours. An increasing trend is to use dexamethasone for “summit day” on high peaks such as Kilimanjaro and Aconcagua, in order to prevent abrupt altitude illness.

Dexamethasone (4mg PO, IM, or IV every 12 hours)

• For those unable to take acetazolamide, dexamethasone may be used as a preventive agent.  It also may be considered for individuals involved in an unusually high-risk situation (i.e., search and rescue personnel airlifted to above 11,000 ft).  Dosages for dexamethasone is the same for PO, IM, and IV routes of administration.  If used for longer than ten days, it must be tapered slowly to prevent withdrawal symptoms.

Nifedipine

Nifedipine both prevents and ameliorates HAPE. For prevention, it is generally reserved for people who are particularly susceptible to the condition. The adult dose for prevention or treatment is 30 mg of extended-release every 12 hours or 20 mg every 8 hours.

Painkillers or Ibuprofen

Acetaminophens, such as Tylenol, can be taken for headaches. Ibuprofen, an anti-inflammatory medicine, can also help. Other than the tight-fit hypothesis previously discussed, other possible mechanisms causing high-altitude headaches include activation of the trigeminovascular system by vasodilatation or inflammatory mediators[rx,rx] or alteration in the blood–brain barrier by inflammatory mediators causing vasogenic edema.]rx] The central role of inflammation in these mechanisms has led to an interest in nonsteroidal anti-inflammatory medications such as ibuprofen.

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What does pantothenic acid do for your body?/Pantothenic Acid is a water-soluble vitamin ubiquitously found in plants and animal tissues with antioxidant properties. Vitamin B5 is a component of coenzyme A (CoA) and a part of the vitamin B2 complex. Vitamin B5 is a growth factor and is essential for various metabolic functions, including the metabolism of carbohydrates, proteins, and fatty acids. This vitamin is also involved in the synthesis of cholesterol, lipids, neurotransmitters, steroid hormones, and hemoglobin.

Vitamin B₅  or Pantothenic acid is a water-soluble vitamin. Pantothenic acid is an essential nutrient. Animals require pantothenic acid in order to synthesize coenzyme-A (CoA), as well as to synthesize and metabolize proteins, carbohydrates, and fats. The anion is called pantothenate. Pantothenic acid is the amide between pantoic acid and β-alanine. Its name derives from the Greek pantothen, meaning from everywhere, and small quantities of pantothenic acid are found in nearly every food, with high amounts in fortified whole-grain cereals, egg yolks, liver, and dried mushrooms. It is commonly found as its alcohol analog, the provitamin panthenol (pantothenol), and calcium pantothenate.

Deficiency Symptoms of Pantothenic Acid / Vitamin B5

Pantothenic acid deficiency has only been observed in individuals who were fed diets virtually devoid of pantothenic acid or who were given a pantothenic acid metabolic antagonist, omega-methyl pantothenic acid. The subjects exhibited various degrees of signs and symptoms, including irritability and restlessness; fatigue; apathy; malaise; sleep disturbances; gastrointestinal complaints such as nausea, vomiting, and abdominal cramps; neurobiological symptoms such as numbness, paresthesias, muscle cramps, and staggering gait; and hypoglycemia and increased sensitivity to insulin.

Symptoms of a vitamin B5 deficiency may include

• Fatigue
• Depression
• Irritability
• Insomnia
• Stomach pains
• Tiredness
• Apathy
• Depression
• Sleep disorders
• Nausea -vomiting
• Numbness
• Muscle cramps
• Hypoglycemia
• Burning feet
• Vomiting
• Upper respiratory infections
• Muscle cramps

Recommended Intakes of Vitamin B5

Intake recommendations for pantothenic acid and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the National Academies of Sciences, Engineering, and Medicine. DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and sex, include:

• Recommended Dietary Allowance (RDA) – Average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.
• Adequate Intake (AI) – Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA.
• Estimated Average Requirement (EAR) – Average daily level of intake estimated to meet the requirements of 50% of healthy individuals; usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them; can also be used to assess the nutrient intakes of individuals.
• Tolerable Upper Intake Level (UL) – Maximum daily intake unlikely to cause adverse health effects.

When the FNB evaluated the available data, it found the data insufficient to derive an EAR for pantothenic acid. Consequently, the FNB established AIs for all ages based on usual pantothenic acid intakes in healthy populations.

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Dietary Reference Intakes for Pantothenic Acid by Life Stage Group (mg/day)

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Food Source of Pantothenic Acid / Vitamin B5

Several food sources of pantothenic acid are listed bellow

*DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration (FDA) to help consumers compare the nutrient contents of products within the context of a total diet. The DV for the values in Table 2 is 10 mg for adults and children age 4 years and older. This value, however, decreases to 5 mg when the updated Nutrition and Supplement Facts labels are implemented. The updated labels must appear on food products and dietary supplements beginning in January 2020, but they can be used now. The FDA does not require food labels to list pantothenic acid content unless a food has been fortified with this nutrient. Foods providing 20% or more of the DV are considered to be high sources of a nutrient.

The U.S. Department of Agriculture’s (USDA’s) National Nutrient Database for Standard Reference website lists the nutrient content of many foods and provides a comprehensive list of foods containing pantothenic acid arranged by pantothenic acid content and by food name.

Health Benefit of Pantothenic Acid / Vitamin B5

• Pantothenic acid – has been used for a wide range of disorders such as acne, alopecia, allergies, burning feet, asthma, grey hair, dandruff, cholesterol-lowering, improving exercise performance, depression, osteoarthritis, rheumatoid arthritis, multiple sclerosis, stress, shingles, aging and Parkinson’s disease. It has been investigated in clinical trials for arthritis, cholesterol-lowering and exercise performance.[Mason P; Dietary Supplements,
• The topical application of pantothenate –  is widely used in clinical practice for wound healing.
• Pantothenic acid deficiency –  Taking pantothenic acid by mouth prevents and treats pantothenic acid deficiency.
• Skin reactions from radiation therapy – Applying dexpanthenol, a chemical similar to pantothenic acid, to areas of irritated skin does not seem to help treat skin reactions from radiation therapy.
• Some research suggests that taking pantothenic acid in combination with pantethine and thiamine does not improve muscular strength or endurance in well-trained athletes.
• There is conflicting evidence regarding the usefulness of pantothenic acid in combination with large doses of other vitamins for the treatment of ADHD.
• Early research suggests that taking dexpanthenol, a chemical similar to pantothenic acid, by mouth daily or receiving dexpanthenol shots can help treat constipation.
• Early research suggests that using specific eye drops (Siccaprotect) containing dexpanthenol, a chemical similar to pantothenic acid, does not improve most symptoms of dry eyes.
• Some evidence suggests that applying gel or drops containing dexpanthenol, a chemical similar to pantothenic acid, reduces some symptoms of eye trauma. However, not all research is consistent.
• Early research suggests that pantothenic acid (given as calcium pantothenate) does not reduce symptoms of osteoarthritis.
• There is inconsistent evidence on the potential benefits of taking pantothenic acid after surgery. Taking pantothenic acid or dexpanthenol, a chemical similar to pantothenic acid, does not seem to improve bowel function after stomach surgery. However, taking dexpanthenol by mouth might reduce other symptoms after surgery, such as sore throat.
• Developing research suggests that pantothenic acid (given as calcium pantothenate) does not reduce the symptoms of arthritis in people with rheumatoid arthritis.
• Early research suggests that using a specific spray (Nasicur) that contains dexpanthenol, a chemical similar to pantothenic acid, helps relieve nasal dryness.
• Early research suggests that using a nasal spray containing dexpanthenol, a chemical similar to pantothenic acid, after sinus surgery reduces discharge from the nose, but not other symptoms.
• Research on the effects of pantothenic acid for preventing skin irritations is not consistent. Some early research suggests that a specific product (Bepanthol Handbalsam) containing dexpanthenol, a chemical similar to pantothenic acid, does not prevent skin irritation when applied to the skin. However, other research suggests that dexpanthenol ointment can prevent skin irritation.
• Early research suggests that using a specific ointment (Hepathrombin-50,000-Salbe Adenylchemie) containing dexpanthenol, a chemical similar to pantothenic acid, as well as heparin and allantoin reduces swelling related to ankle sprains.
• Alcoholism.
• Allergies.
• Hair loss.
• Asthma.
• Heart problems.
• Carpal tunnel syndrome.
• Lung disorders.
• Colitis.
• Eye infections (conjunctivitis).
• Convulsions.
• Kidney disorders.
• Dandruff.
• Depression.
• Diabetic problems.
• Enhancing immune function.
• Headache.
• Hyperactivity.
• Low blood pressure.
• Inability to sleep (insomnia).
• Irritability.
• Multiple sclerosis.
• Muscular dystrophy.
• Muscle cramps.

References

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How does allopurinol prevent tumor lysis syndrome?/Tumor lysis syndrome (TLS) is characterized by a massive tumor cell death leading to the development of metabolic derangements and target organ dysfunction? TLS can occur as a result of cancer treatment or spontaneously. Blood cancers constitute the vast majority of TLS cases because of the sensitivity to therapy and rapid division rates.

Tumor lysis syndrome (TLS) is a potentially life-threatening condition that occurs in oncologic and hematologic patients with large tumor burden, either due to cytotoxic therapy or, less commonly, spontaneously because of massive tumor cell lysis. TLS is clinically characterized by acute renal failure, hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. While limited options are available for treating TLS, identifying patients at high risk for developing TLS and prevention in high-risk patients remain an important aspect in the treatment of cancer patients. In general, treatment of TLS consists of intensive hydration, stimulation of diuresis, and, more specifically, in the use of allopurinol and rasburicase.

Tumor lysis syndrome (TLS) describes the pathological sequela of the rapid lysis of tumor cells. The shift of potassium, phosphorus, and nucleic acid material into the extracellular space can rapidly overcome existing homeostatic mechanisms, leading to acute kidney failure, arrhythmia, and death. TLS is the most common oncologic emergency, and although commonly seen in the context of initial chemotherapeutic treatment of hematologic malignancies, increasing recognition is being paid to the occurrence of spontaneous TLS and TLS secondary to treatment of bulky solid tumors.^[rx,rx]

Tumor lysis syndrome is a group of metabolic abnormalities that can occur as a complication during the treatment of cancer,^[rx] where large amounts of tumor cells are killed off (lysed) at the same time by the treatment, releasing their contents into the bloodstream. This occurs most commonly after the treatment of lymphomas and leukemias. In oncology and hematology, this is a potentially fatal complication, and patients at increased risk for TLS should be closely monitored before, during, and after their course of chemotherapy.

Pathophysiology

The pathophysiology of tumor lysis syndrome is complicated. Tumor lysis syndrome is caused by the massive release of intracellular ions such as potassium, phosphorus, and nucleic acids that have been metabolized to uric acid. The main organ is responsible for the excretions of these substances in the kidney. When the compensatory response of the kidney is exhausted as a result of the massive release of intracellular ions, uric acid obstructive uropathy develops which can then progress to acute kidney injury.

Molecules called nucleotides comprise DNA. These nucleotides are units made of a phosphate group, a sugar group, and a nitrogen base. The nitrogen base is adenine, thymine, guanine or cytosine. Adenine and guanine are purines while thymine and cytosine are pyrimidines. Ribonucleic acid, however, is made up of a ribose sugar and a nitrogen base adenine, thymine, and uracil.

The metabolism of the purines adenine and guanine in a stepwise process leads to the production of xanthine. Adenine is metabolized to hypoxanthine whereas guanine is metabolized to xanthine. Xanthine is then further metabolized into uric acid in a reaction that is catalyzed by xanthine oxidase. Most mammals have the enzyme urate oxidase that can transform uric acid to allantoin which is a more soluble substance that can be easily excreted by the kidney. Human beings lack this enzyme.

Due to the rapid turnover of tumor cells, there is an overwhelming production of uric acid which then crystallizes in the renal tubules causing obstructive uropathy from and decreased glomerular filtration rate. In rat models, urate nephropathy causes an increase in both proximal and distal tubule pressure. Peritubular capillary pressure and vascular resistance also increase. Uric acid scavenges nitric oxide which is a potent vasodilator. The scavenging of nitric oxide produces vasoconstriction and kidney ischemia. Uric acid is also a potential pro-inflammatory agent and can cause the release of other cytokine-like tumor necrosis factor-alpha, protein I. These cytokines attract white blood cells and facilitate further injury to the kidney.

Electrolyte Imbalance

Hyperkalemia

The concentration of potassium within the cell is about 120 to 130 meq/L. The lysis of tumorous cells leads to a massive release of intracellular potassium. The excess potassium is usually taken up by the liver and skeletal muscle. The rest is excreted via the gastrointestinal system or the kidney. The obstructive uropathy from uric acid salts can limit the excretion of potassium. Sometimes the hyperkalemia from the solid tumor can reach a potentially life-threatening level. The risk of hyperkalemia is cardiac arrest from arrhythmia.

Hyperphosphatemia

Hyperphosphatemia is another electrolyte imbalance associated with tumor lysis syndrome. The nucleic acid has a phosphate group, and the breakdown of the tumorous cell will lead to the release of a significant amount of phosphorus into the bloodstream. Most of the phosphorus is really excreted. This ability of the kidney to handle a high load of phosphorus is inhibited by acute kidney injury or chronic kidney disease.

Hyperphosphatemia is less common in spontaneous tumor lysis syndrome than those induced by chemotherapy. It leads to the chelation of calcium causing hypocalcemia. Deposition of calcium and phosphorus salts in the kidney and soft tissues can also occur.

Hypocalcemia

Hypocalcemia in tumor lysis syndrome is mostly secondary to the chelation of phosphorus. This condition is more potentially life-threatening than hyperphosphatemia. Possible complications from hypocalcemia include arrhythmia, tetany, seizure, and death. The calcium level might still be relatively low even after the normalization of the phosphorus level because of a deficiency of 1, 25 Vitamin D.

Causes of Tumor Lysis Syndrome

Symptoms of Tumor Lysis Syndrome

Hyperkalemia – Potassium is mainly an intracellular ion. High turnover of tumor cells leads to a spill of potassium into the blood. Symptoms usually do not manifest until levels are high (> 7 mmol/L) [normal 3.5–5.0 mmol/L] and they include

• cardiac conduction abnormalities (can be fatal)
• severe muscle weakness or paralysis

Hyperphosphatemia – Like potassium, phosphates are also predominantly intracellular. Hyperphosphatemia causes acute kidney failure in tumor lysis syndrome, because of deposition of calcium phosphate crystals in the kidney parenchyma.

Hypocalcemia – Because of the hyperphosphatemia, calcium is precipitated to form calcium phosphate, leading to hypocalcemia. Symptoms of hypocalcemia include (but are not limited to):

• Tetany
• Sudden mental incapacity, including emotional lability
• Parkinsonian (extrapyramidal) movement disorders
• Papilledema
• Myopathy

Hyperuricemia^[rx] and hyperuricosuria. Massive cell death and nuclear breakdown generate large quantities of nucleic acids. Of these, the purines (adenine and guanine) are converted to uric acid via the purine degradation pathway and excreted in the urine. However, at the high concentrations of uric acid generated by tumor lysis, uric acid is apt to precipitate as monosodium urate crystals.

• Acute uric acid nephropathy (AUAN) – due to hyperuricosuria has been a dominant cause of acute kidney failure but with the advent of effective treatments for hyperuricosuria, AUAN has become a less common cause than hyperphosphatemia. Two common conditions related to excess uric acid, gout and uric acid nephrolithiasis, are not features of tumor lysis syndrome.
• Lactic acidosis.^[rx][rx]
• Pretreatment spontaneous tumor lysis syndrome. This entity is associated with acute kidney failure due to uric acid nephropathy prior to the institution of chemotherapy and is largely associated with lymphoma and leukemia. The important distinction between this syndrome and the post-chemotherapy syndrome is that spontaneous TLS is not associated with hyperphosphatemia.
• One suggestion for the reason for this is that the high cell turnover rate leads to high uric acid levels through nucleobase turnover but the tumor reuses the released phosphate for the growth of new tumor cells. In post-chemotherapy TLS, tumor cells are destroyed and no new tumor cells are being synthesized

TLS is most common during cytotoxic treatment of hematologic neoplasms.^[rx]

• Dark urine reduced urine output or flank pain
• Lack of appetite and fatigue
• Numbness, seizures, or hallucinations
• Muscle cramps and spasms
• Heart palpitations symptoms are generally nonspecific and can include:
• Kidney failure and death can occur, especially if TLS is left untreated.
• TLS is diagnosed based on blood tests, along with signs and symptoms. Its onset may be subtle, with only a few abnormal laboratory values, but it can also present with frank kidney and organ failure.
• Nausea with or without vomiting

Diagnosis of Tumor Lysis Syndrome

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Laboratory tumor lysis syndrome: abnormality in two or more of the following, occurring within three days before or seven days after chemotherapy.

Alkalinization of urine

References

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