Mind Over Gut: The Impact of Stress and Sleep on Peptic Ulcer Disease

Everyone is impacted by the pervasive condition known as stress. H. Selye is credited for defining stress as an immediate danger to an organism's balance. Real (physical) or perceived (psychological), it might be caused by internal or external events. Stress is significant because it triggers adaptive reactions that protect the internal environment's stability and guarantee the organism's existence(1). Stress-induced gastritis is also known by several other names, such as stress-related erosive syndrome, stress ulcer syndrome, and stress-related mucosal disease. It is very important in critically ill patients or in those subjected to severe physiological stress. This condition leads to the development of mucosal erosions along with superficial hematomas, thus giving rise to gastrointestinal bleeding that may range from trivial to severe and requiring blood transfusions if not managed promptly(2). Stress can impact various gastrointestinal functions, which includes gastric acid production, intestinal movement, mucosal permeability, barrier function, visceral sensitivity, and mucosal blood circulation(3-5)(Fig.1).

Fig 1: Effect of stress on gastrointestinal functions. Stress has impact on important physiological functions of gut including gut motility, secretion, visceral sensitivity, mucosal blood flow. In addition, stress modifies gut microbiota and enhances paracellular permeability

According to initial research, emotional factors play a part in the formation of stomach ulcers(6-7).There have been reports that psychological stress can cause the production of stomach acid(8).The significant relationship between the gut microbiota and stress has been demonstrated recently. It's interesting to note that bacteria may react directly to host signals associated with stress. Catecholamines have been shown to change the pathogenicity, proliferation, and movement of both commensal and pathogenic bacteria. Therefore, stress may have an impact on how these germs infect various hosts(9).

TYPES OF STRESS ULCER

1. PHYSIOLOGICAL STRESS
   Any unforeseen circumstance that compromises a cell's or an organism's equilibrium is referred to as physiological stress. It can be separated into three categories: ageing, intrinsic developmental stress, and stress from the environment.
2. THE ULCER OF CUSHING
   A Cushing's ulcer is a single, deep ulcer in the oesophagus, duodenum, or gut that may be brought on by damage to the central nervous system.
3. CURLING'S ULCER
   Acute gastric erosion, or Curling's ulcer, is a consequence of catastrophic burns when ischemia and gastric mucosal cell necrosis (sloughing) are caused by decreased plasma volume(Fig. 2).

Fig 2: Type of Peptic Ulcer Disease and common risk factor

Regarding the connection with stress and gastroenteritis, the vast majority are aware of the close relationship between the gut and the central nervous system. The appearance of various gastrointestinal symptoms, including dyspepsia, diarrhoea, or abdominal discomfort, is known to occur when people are under stress. William Beaumont's preliminary evaluation of the injured soldier with the gastric fistula demonstrated that anxiety or fury can have a major impact on the physiology of the stomach, particularly on the release of acid(10).The nineteenth-century discovery of the enteric nervous system (ENS) was a significant advance in our understanding of the relationships between the gut and the central nervous system (CNS). The ENS (sometimes referred to as the "little brain") is essential for controlling the physiological processes of the gut, such as the release, secretion, and motility of several hormones and neuropeptides(11).

Fig. 3. Impact of stress on brain-gut-microbiota axis. There is a bidirectional interaction between braingut axis and gut microbiota

The brain-gut axis (BGA) refers to the various parallel channels that the brain and gut use to interact, including the autonomic nervous systems (ANS), the hypothalamus pituitary-adrenal axis (HPA), and other linkages(12-13) (Fig. 3). There is compelling evidence from earlier research that stress exposure may be the cause of the dysregulation of the BGA, which in turn may result in various gastrointestinal disorders(14).Corticotrophin releasing factor (CRF) is a key regulator of the immunological, behavioural, and endocrine responses to stress. The CRF family of peptides exhibits strong biologic effects and is expressed in both the stomach and the central nervous system. By modifying inflammation, increasing gut permeability, contributing to visceral hypersensitivity (increased pain perception), and altering gut motility, CRF has strong impacts on the gut. The beginning phase of HPA activation involved in the stress response is CRF production in the hypothalamus. This is the main endocrine system that reacts to stress. In response to CRF, the pituitary gland releases adrenocorticotropic hormone (ACTH), which causes the adrenal glands to release more cortisol, a stress hormone(15).

FIG  4: The central nervous system (CNS, brain, and spinal cord) and the enteric nervous system (ENS) communicate continuously and in both directions.

The central nervous system (CNS, brain, and spinal cord) and the enteric nervous system (ENS) communicate continuously and in both directions. Through the sympathetic nervous system's efferent motor routes of the prevertebral ganglia and the parasympathetic nervous system's afferent sensory pathways of the vagus nerve, the gut and the brain can communicate. The intestinal microbiome also influences the brain-gut axis. By affecting the ENS and producing chemicals that can pass through the blood-brain barrier, the microbiota can either directly or indirectly affect the central nervous system (CNS) through the vagus nerve. As

a neurotransmitter in the ENS and CNS and a hormone that circulates throughout the body, serotonin (5-HT) plays a crucial role in brain-gut communication. Tryptophan hydroxylase 1 (TPH1) in enterochromaffin (EC) cells and TPH2 in neurones synthesise 5-HT, which is mainly inactivated by the serotonin reuptake transporter (SERT) following reuptake. TPH, tryptophan hydroxylase; MAO, monoamine oxidase; 5-HT, 5-hydroxytryptamine; 5-HIAA, 5-hydroxyindoleacetic acid; Trp, tryptophan(Fig. 4).

Additionally, there is proof that gut bacteria maintain the two-way communication between the gut axis and brain components. Stated differently, stress alters the bacterial ecology, but the gut bacteria also alter motility, permeability, and visceral sensitivity, which may have a significant impact on the BGA. The BGA and microbiota interact via a variety of methods: 1) endocrine message by direct contact with mucosal cells, 2) immune message through immune cells, and 3) neural message through contact with neural terminals(16). Stress alters the microbiota's makeup by causing alterations to neurotransmitter and proinflammatory cytokine levels, which may have an indirect or direct impact on the microbiota. For instance, norepinephrine makes certain bacteria, such as C. jejuni or E. coli, more virulent. Certain probiotics may prevent intestinal permeability and hypersensitivity brought on by stress exposure, and gut bacteria may regulate pain perception. The remarkable interplay of stress, the immune system, and the gut microbiota is demonstrated by several lines of evidence(17).Mast cells are crucial for the translation of stress signals to the human stomach. Remarkably, these cells carry CRF receptors on their surface and release several significant mediators, suggesting a significant connection between stress and these cells(18,19).

 Lastly, prolonged and excessive activation of the CNS's stress response regions is linked to chronic stress exposure. The brain regions in charge of gut pain perception may possibly undergo irreversible alterations as a result of this exposure. Techniques known as functional magnetic resonance imaging (MRI) can be used to demonstrate these changes(20).

Pathophysiology: Clinical Consequences Of The Dysregulation Of Brain-Gut-Microbiota Axis In The Upper Gastrointestinal Tract

The development of a wide range of gastrointestinal disorders, including gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), IBD, IBS, and even food allergies, may result from the dysregulation of BGA brought on by stress(21,22)(Fig. 5). PUD may develop as a result of exposure to stressful life events. Patients with ulcers have a greater tendency to be bereaved, divorced, or separated. It has been demonstrated that stress exposure may contribute to PUD and may hinder the gastric and duodenal defences against the damage caused by an attack from acid and pepsin damage, even though Helicobacter pylori (Hp) and nonsteroidal anti-inflammatory drugs (NSAID) are the major causes of the condition(23).

Fig 5: pathophysiological effects of stress-induced alteration of the brain-gut microbiota axis. Stress exposure disrupts the brain-gut axis (BGA), which contributes to the development of several gastrointestinal disorders, such as food allergies, irritable bowel disease, inflammatory bowel disease, peptic ulcer disease, and gastroesophageal reflux disease.

Variations in gastric acid production, decreased mucosal blood flow, decreased HCO3-secretion, decreased acid back diffusion, decreased proliferation and restitution of the wounded mucosa, and changes in stomach motility are some of the potential contributing variables. Stress was thought to be one of the main risk factors for peptic ulcers prior to the discovery of HP(24). Stress ulcerations, a unique type of ulceration brought on by prolonged exposure to stress, are frequently seen among patients in intensive care units(25).

Through the manipulation of several key neuropeptides (such as CGRP) involved in the protection of the gastric mucosa, changes in the secretion of gastric contents, regenerating of the gastric mucosa, and changes in mucosal blood flow, our own research showed that stress may have a significant impact on the BGA(26,27)(Fig.6).

Fig. 6.  Effect of disruption of brain-gut axis on ulcer healing. Exposure to stress and the resulting disturbance of brain-gut axis may have negative effect on ulcer healing including changes in gastric secretion, proliferation rate at the ulcer edge and angiogenesis

According to  analysis, the number of prevalent cases of PUD in 2019 was 8.09 million (95% UI 6.79 to 9.58 million), a 25.82% increase from 1990 [6.43 million (95% UI 5.41 to 7.63 million)]. Additionally, the age-standardized prevalence rate decreased from 1990 [143.37 per 100,000 (95% UI 120.54 to 170.25 per 100,000) population] to 99.40 per 100,000 (95% UI 83.86 to 117.55 per 100,000) population in 2019. There was a 27.3% increase in the number of PUD incident cases worldwide between 1990 and 2019, rising from 2.82 million (95% UI 2.36 to 3.30 million) to over 3.59 million (95% UI 3.03 to 4.22). At 63.84 (95% UI 54.09 to 75.54) per 100,000 people in 1990 and 44.26 (95% UI 37.32 to 51.87) per 100,000 population in 2019, the global age-standardized incidence rate of PUD, however, shown a declining trend. With an age-standardized rate of 74.40 (95% UI 68.96 to 81.95) DALYs per 100,000 population in 2019, PUD was responsible for over 6.03 (95% UI 5.59 to 6.64) million DALYs worldwide. Compared to 1990, the age-standardized rate of DALYs dropped by 60.64%. Deaths from PUD also showed similar patterns.

Males had a higher age-standardized prevalence rate and more prevalent cases than females in every year between 1990 and 2019. Nonetheless, the gap between the two groups narrowed, primarily as a result of boys' age-standardized prevalence rate and prevalent case count declining more quickly than females'. In total, there were 4.17 (95% UI 3.49 to 4.97) million prevalent cases in males and 3.92 (95% UI 3.29 to 4.64) million prevalent cases in females in 2019.

Between males and females, the prevalence of cases was 1:0.94. In 2019, the age-standardized prevalence rates for males and females were 104.98 (95% UI 88.26 to 124.10) and 94.23 (95% UI 79.10 to 111.93) per 100,000 population, respectively(28)(Fig. 7).

Fig 7: Prevalence rates and deaths with age-standardized rate changes in all years from 1990 to 2019. a The numbers of prevalent cases and age-standardized prevalence rates in males and females. b The numbers of deaths and age-standardized death rates in males and females

PROGNOSIS

Studies reveal a robust correlation between the prevalence of PUD and perceived stress. According to a long-term study of adults in the United States, those who reported high levels of stress were 1.8 times more likely to get ulcers than those who reported lower levels of stress. Additionally, the study revealed a graded association between ulcer occurrence and stress levels(29).In a similar vein, a Danish cohort study found that those who felt a lot of stress were more than twice as likely to get PUD than people who felt less stress. Even after controlling for variables including age, gender, socioeconomic level, use of NSAIDs, and smoking, this link persisted(30).

Prognostic Elements

Stress Level and Corresponding Illness:

Stress-related PUD is more likely to occur in critically ill patients, particularly those  in intensive care units with illnesses like sepsis or multiple organ failure syndrome. Ulcers can develop as a result of severe physical stressors including major operations, severe burns, or severe brain trauma(31).

Aspects of Psychology

An elevated risk of PUD has been associated with psychiatric disorders such as depression and anxiety as well as emotional stress. According to studies, psychological stress may have an impact on PUD's development and course.

Complications

Gastrointestinal Bleeding: Hematemesis (blood in the vomit) and melena (black, tarry faeces) are signs of bleeding ulcers, which is a serious problem in PUD associated with stress. In severe cases, surgery or blood transfusions can be required.(Fig 8)

Fig 8: Gastrointestinal Bleeding

Perforation: An incision in the stomach or duodenal wall caused by an ulcer may result in peritonitis, a serious abdominal infection that needs to be treated right once(Fig 9).

     A)                          B)

          C)                     D)

It can also be helpful to address psychological stress with techniques like emotion management training or cognitive-behavioral therapy. According to a study, emotion management training significantly decreased the severity of pain and enhanced PUD patients' quality of life.

Due to the underlying serious condition, patients with stress ulcers typically have a bad prognosis. Furthermore, GI bleeding in these individuals as a result of mucosal disease brought on by stress is linked to higher morbidity and death on its own.  These patients frequently have worse results because they are too unstable for sophisticated endoscopic or surgical techniques to stop GI bleeding. Therefore, the mainstay of treating stress-induced gastropathy continues to be active preventive treatments for the right patient population at risk of stress ulceration(33,34).

PEPTIC ULCER DISEASES AS THE IMPORTANT MANIFESTATION OF STRESS IN GASTROINTESTINAL TRACT

Indigestion, sometimes known as dyspepsia, is the hallmark sign of a stomach ulcer.

Pain or discomfort in the stomach region is a result of indigestion. This symptom is sometimes confused with heartburn, which can happen simultaneously. Heartburn may be caused by acid reflux or gastroesophageal reflux disease. People

will experience it in the lower chest, a little higher up from the stomach. Although they can still be hazy, stomach ulcer symptoms are typically more pronounced than heartburn symptoms.

A dull or burning pain in the middle of the abdomen is another common symptom of an ulcer. The pain is sometimes described as chewing or biting. Some people could talk about feeling hungry.

Additional symptoms include

• vomiting and nausea
• inexplicable weight loss
• Burping
• Bloating
• feeling full
• having trouble drinking as much fluid as usual,
• tarry, bloody faeces
• chest pain
• exhaustion
• not eating due to pain

While severe ulcers can result in excruciating pain and major problems, minor ulcers might not show any symptoms at all. It might be challenging to differentiate the symptoms of a stress ulcer from those of another sickness because those who have them are already ill.

A stress ulcer's symptoms include:

• upper abdominal pain
• pain that improves or worsens with food
• bloating or unusual fullness
• nausea or vomiting
• anaemia signs, including pale skin
• shortness of breat

Fig 10: Symptoms of PUD

Some ulcers bleed profusely, resulting in potentially fatal blood loss. This blood loss might be fatal for those who are already battling severe injuries(Fig. 10).

DIAGNOSIS

 In practical terms, both noninvasive and invasive methods are used in the diagnosis of stress-related disorders in the upper gastrointestinal tract(35).

The non-invasive methods include

• routine blood tests (complete blood count, chemistries, thyroid function, stool diagnostic)
• celiac disease serology (transglutaminase IgA); 13C urease breath test to rule out HP infection; elastase-1 in stool to rule out exocrine pancreatic insufficiency; H2 breath test with glucose to rule out small intestinal bacterial overgrowth (SIBO)
• H2 breath test with glucose to rule out carbohydrate malabsorption
• sucrose permeability test to assess the function of the intestinal barrier
• gut motility assessment using lactulose.

Upper gastrointestinal tract endoscopy and intestinal endoscopy (capsule endoscopy, push-and-pull enteroscopy) are examples of invasive procedures(36).

Gastric ulcers are staged using the Forrest classification; which is mostly determined by endoscopic results.

Acute Haemorrhage:

• Forrest Ia: Active Stunter

The following are indicators of recent bleeding:

• Forrest IIa: A visible, non-bleeding vessel
• Forrest IIb: An adherent clot
• Forrest IIc: Flat, pigmented haematin on the ulcer base.

Lesions Without Active Bleeding:

• Forrest III: Unblemished lesions

METHODS OF ENDOSCOPIC TREATMENT

INJECTION THERAPY

There are three types of endoscopic treatment: mechanical, heat, and injection. Epinephrine, sclerosants (polidocanol, pure ethanol), and tissue adhesives (thrombin/fibrin glues) are the components of injection therapy. The most popular technique for hemostasis is epinephrine injection. Compared to other techniques, it is simple to use and necessitates less cooperation between the assistant and the endoscopist. The tampon effect is the primary reason why epinephrine injection works well for obtaining early hemostasis.But when it comes to stopping more bleeding, epinephrine monotherapy is less successful than other monotherapies like electrocoagulation, clips, or fibrin glues. It is also much more successful to use a second modality, like electrocoagulation or clips, than just epinephrine to prevent more bleeding and surgery(37)(Fig. 11). Nowadays, most people agree that epinephrine alone is insufficient and ought to be used in conjunction with another treatment. In clinical practice, epinephrine injections are typically used prior to other treatments in order to reduce or halt bleeding and enhance visualisation for later treatments(38).

Fig. 11: Endoscopic findings. (A) Oozing by gastric ulcer was observed at distal antrum. (B) Oozing was stopped after injection of 1:10,000 diluted epinephrine solution.

THERMAL THERAPY

There are two types of thermal contact therapy: contact and noncontact. Bipolar electrocoagulation and heater probes are examples of contact procedures, while argon plasma coagulation is an example of a noncontact method(39). Initial hemostasis can be achieved with considerable effectiveness using thermal treatments, which also lower the risk of more bleeding, surgery, and death(37)(Fig.12).

As of right now, there are no discernible differences between the various thermal modalities. According to two studies, thermal therapy plus an epinephrine injection proved to be more successful than thermal therapy alone(40).

Fig.12: Endoscopic findings. (A) A non-bleeding visible vessel on ulcer base was observed at upper body of stomach. (B) Argon plasma coagulation was performed in the visible vessel.

MECHANICAL THERAPY

Clips have been proven to be less effective than thermal therapy but more successful than epinephrine injection in preventing more bleeding and surgery(37).Clips probably don't cause tissue damage, which is advantageous compared to sclerosants and heat treatments. Clips are typically thought to be more costly than the other hemostatic techniques, and the Korean National Health Insurance does not currently compensate them. Additionally, for the application to be successful, the helpers must be trained in managing the clip. The difficulty of applying endoclips in fibrotic tumours is another drawback. Additionally, endoclips now in use only provide the deployment of a single clip; if many clips are required, repeated device passage may lengthen the process time. For improved clip control while using an endoclip, the target and the clip should be near the endoscope. Before deployment, suction might be used to gather as much tissue as possible surrounding the lesion(41)(Fig.13).

Fig.13: Endoscopic findings. (A) A spurting was observed at duodenal ulcer. (B) A spurting was stopped by apply of endoclip

Anxiety Management Training

The four-session anxiety management programme was modelled after Richardson's (1976) programme. With the therapist's assistance, the patients (A) explored their illogical beliefs that contribute to their anxiety (Ellis, 1973; Richardson, 1976) and negative self-talk during stressful situations, and (B) created and composed meaningful self-talk and personal beliefs. Assertiveness Training: The second four sessions were conducted in accordance with the 1971 Lazarus procedure. Two aspects were highlighted in these sessions: (A) cognitive reconstruction that addressed misunderstandingsregarding assertiveness and the negative effects of nonjudgment (especially in relation to ulcer-related issues), and (B) employing assertive behaviours in daily contexts.

The necessity of developing self-awareness took up a large portion of the courage training time. Particular emphasis was placed on chronic resentment with sporadic episodes of rage and the ensuing uncomfortable guilt. The control group received the same care as before. For eight weeks, patients in this group were contacted once a week for fifteen minutes, but no significant psychological therapies were carried out. Following the post-test and follow-up, the control group also received the same interventions in accordance with the protocol.The procedures carried out for the experimental and control groups are summarised in (Fig. 14).

Fig 14: Coping Style Scale at pretest And Anxiety Management Training

STRESS MANAGEMENT THERAPY

The employment of methods, approaches, or programmes designed expressly to lower stress levels, avoid stress, or deal with circumstances or occurrences that can raise stress levels is known as stress management treatment(42).  

Psychotherapy (talk therapy) for stress and relaxation training are two examples.
Stress therapy may be helpful when someone is:

• Dealing with stress for an extended length of time
• High levels of stress
• going through life transitions or changes
• anticipating changes or transitions in the future

One of the numerous advantages of stress therapy is that it lowers the dangers of stress. Stress has detrimental consequences on one's physical, mental, emotional, and social well-being as well as one's quality of life. The following are a few instances of the detrimental impacts of stress:

• Enhanced rage
• unfavourable relationships with family, friends, or other people
• difficulty sleeping
• A higher risk of being ill

Every bodily system—digestion, reproduction, respiration, bones and muscles, the heart and circulation, nerves, tissues, organs, and hormones—is adversely affected by stress(43).

Reducing stress, preventing and addressing these harmful effects, improving mood, and improving your quality of life are all possible with stress therapy(44).

Benefits of stress therapy include:

• Better mood
• Improved immune system function
• Better sleep
• Better digestion
• Chronic disease management
• Improved physical health
• Improved relationship interactions
• Hypotension
• Reduced pain
• Increased productivity
• Improved mental and emotional health

STRESS THERAPY TYPE

Stress management therapy comes in a variety of forms. Talk therapy techniques that can concentrate on stress specifically include cognitive behavioural therapy (CBT), mindfulness-based cognitive therapy (MBCT), and psychodynamic therapy(45).Preventive stress management is instruction given prior to the stressful event that teaches how to identify, anticipate, and react to stressors, including coping mechanisms.

Cognitive Behavioral Therapy (CBT)

One form of talk therapy that is frequently used for stress management is cognitive behavioural therapy. This approach emphasises the relationship between ideas, emotions, and behaviours and how altering one can alter the others and their results.
CBT focuses on recognising flawed cognitive processes that influence feelings and actions.It might involve observing, for instance, how the dread of doing something can be triggered by the belief that one is not good at it(46).  People can alter their thoughts, feelings, and behaviours in ways that encourage relaxation and lessen stress by participating in cognitive behavioural therapy (CBT) programmes and therapies designed especially for stress. It has been discovered that CBT-based stress management lowers stress and anxiety levels while enhancing psychological health and confidence(47)(Fig.15).

Fig. 15: cognitive behavioural therapy (CBT) programmes and therapies designed

Mindfulness-Based Cognitive Therapy (MBCT)

Awareness of one's internal thoughts and emotions as well as one's exterior surrounds and environments is the main goal of mindfulness. For instance, it can involve paying attention to the sensation of the sun and wind against your skin or taking note of ideas that occur to you(48).A form of talk therapy called mindfulness-based cognitive therapy blends cognitive behavioural therapy with mindfulness techniques like meditation(49)(Fig.16)

Fig. 16: mindfulness-based cognitive therapy

Mindfulness-Based Stress Reduction (MBSR)

In order to prevent and treat stress, mindfulness-based stress reduction integrates mindfulness practices with stress management strategies(Fig.17). It could involve bodily awareness, yoga, meditation, relaxation, and other methods. It has been demonstrated that MBSR enhances quality of life and lowers stress, anxiety, depression, and burnout(50).

Fig.17: Mindfulness-Based Stress Reduction

Psychodynamic Therapy

Talk therapy that examines a person's past experiences, feelings, and beliefs and how they relate to their present state of mind is called psychodynamic therapy. Increased self-awareness and comprehension of how the past shapes present behaviour are the main objectives of psychodynamic therapy.People who receive this kind of therapy may be able to comprehend how their past affects their stress levels and coping mechanisms.People can prevent and manage stress in a variety of ways besides stress therapy. Anything that encourages relaxation can fall under this category, including(51)(Fig. 18):

• Taking a walk
• Reading a book
• Enjoying a personal hobby
• Getting physical activity, such as bike riding, hiking, or swimming
• Volunteering
• Spending time in nature(52).

Some other practices that can help you prevent and manage stress include the following:

• Avoid drugs and alcohol
• Create, communicate, and hold boundaries
• Connect with loved ones
• Meditate
• Eat a well-balanced diet
• Exercise regularly
• Follow a routine or keep a daily practice
• Help others and volunteer
• Manage your expectations for yourself
• Make time for hobbies
• Practice relaxation techniques
• Prioritize self-care(53).

Fig. 18: Mindfulness-Based  Art Therapy

Relaxation

The opposite of stress is the relaxation reaction, which is brought on by employing relaxation techniques to quiet the body and mind(54).Numerous relaxation methods are available to assist lower and even avoid stress. These can be used in conjunction with stress therapy, on their own, or in combination with other relaxation methods.Examples of relaxation techniques include:

• Body awareness, which emphasises breathing and muscle relaxation
• Music and art therapy
• Prayer and mantras
• Yoga or tai chi
• meditation and visualisation
• massage

Breathing Techniques

Breathing exercises can ease tension and encourage relaxation. Numerous breathing techniques exist, each with its own unique method of action. One yoga breathing method that has been demonstrated to have a calming impact and lower stress is ujjayi breathing, often known as ocean breathing(55).

• Among the breathing exercises for stress relief and relaxation are:
  Abdominal breathing, sometimes referred to as diaphragmatic breathing or belly breathing, is a breathing method in which air is drawn into the diaphragm and the abdomen is expanded by breathing in through the nose and out through the mouth.
• Ujjayi breathing, also known as ocean breathing, is a yoga breathing method in which you breathe in and out through your nose for the same amount of time.
• 4-4-4 breathing technique: This count-based breathing method consists of four counts of inhalation, four counts of holding the air in, four counts of exhalation, four counts of letting the lungs remain empty, and then four repetitions.

PHARMACOTHERAPEUTIC APPROACH

The aim of management is to prevent stress gastritis. Keep an eye on the stomach contents' pH (aim for >4.0). If the patient was previously receiving prophylactic therapy, think about doubling the dosage of the medication used to lower stomach acid levels if the pH level is below the desired pH.

The following drugs are used to treat gastritis brought on by stress:

Sucralfate: The main preventative agent

histamine 2 (H2) receptors blocker:  There are anticholinergic antihistamines. This indicates that they inhibit acetylcholine's action. The stomach releases acid as a result of acetylcholine's stimulation of Trusted Source mechanisms. (for instance, nizatidine, cimetidine, ranitidine, and famotidine)

Proton pump inhibitor: This class of medications lowers stomach acid. When PPI users quit taking the medication, their elevated gastrin levels may cause their stomach acid to rise. As a result, it's critical to stick with treatment for as long as your doctor advises. (for instance, pantoprazole and esomeprazole) When it comes to HP infections, proper eradication should be promoted because it can help certain individuals with functional dyspepsia by reducing their symptoms(56,57)(Table 1)(58-64).

Table 1: Agents for stress ulcer

DIET

Making dietary adjustments can help stop stomach ulcers from appearing.
More of the following nutrients should be consumed by those who are susceptible to stomach ulcers:

• Vegetables and fruits: Consuming a range of fruits and vegetables is essential for maintaining a healthy lining of the digestive tract. These foods have cytoprotective and anti-inflammatory qualities, are high in antioxidants, and prevent the release of acids. According to a 2017 study, each of these is crucial for both avoiding and curing ulcers.
• Fibre: Soluble dietary fiber-rich diets lower the risk of stomach ulcers.
• Probiotics: Foods like probiotic yoghurt that have active

microorganisms in them can help lessen Helicobacter pylori (H. pylori) infections. Probiotics have been demonstrated to marginally alleviate antibiotic side effects including gastrointestinal symptoms.

• Vitamin C: When taken in tiny levels over an extended period of time, this potent antioxidant may help eradicate H. pylori. Vitamin C is abundant in fruits, legumes, and vegetables including tomatoes and oranges.

Because both alcohol and caffeine increase the production of stomach acid, avoiding them can also help lower the risk. Stomach ulcers may result from this.

However, for the best results, dietary suggestions should be followed in conjunction with a treatment plan rather than solely depending on nutrition(Fig.19).

Fig. 19: Dietary Adjustments for Ulcer