(1) INTERNAL MEDICINE PRACTICE "DR BASTAĆ" ZAJEČAR; (2) SPECIALIST PRACTICE FOR INTERNAL MEDICINE "DR PAVLOVIĆ CARDIOLOGY" BELGRADE

Abdominal pain is one of the most common symptoms of various diseases of the abdominal cavity or diseases outside of it. It represents a great diagnostic challenge for both primary healthcare physicians and clinical specialists. The cause is very often completely benign, but it can also be a life-threatening condition that must be recognized early and appropriate measures taken. A precise history and detailed clinical examination are key and indispensable parts of the diagnostic process, as they determine the level of urgency and the scope of further consideration. We must be particularly cautious in the treatment of the elderly, women of reproductive age, and immunocompromised individuals, because the clinical picture of otherwise common diseases can be atypical, and at the same time we must also consider rarer and specific causes of abdominal pain. In these groups, abdominal pain can be acute, subacute, or chronic. The cause can be organic, but when the cause cannot be identified despite extensive diagnostics, we speak of functional abdominal pain syndrome. Depending on pathophysiological mechanisms, we distinguish visceral, somatic, and referred pain. Due to the specificity of treatment, a special entity is the so-called acute abdomen, which is a life-threatening condition and requires urgent treatment.
Abdominal pain is classified as acute or chronic based on an arbitrary time frame of approximately 12 weeks. Establishing a differential diagnosis is very complex and requires a thorough history and comprehensive physical examination. However, the cause remains unknown in 30% of cases [1].
It is necessary to analyze abdominal pain with special emphasis on six characteristics: onset, progression, migration, character, intensity, and localization. The onset of pain
The onset of pain can be: sudden, rapid, and gradual. Sudden pain occurs in a second; typical for perforation of a peptic ulcer, rupture of an ectopic pregnancy, mesenteric infarction, aneurysm rupture. Rapid onset of pain – develops over several minutes; seen in cholecystitis, pancreatitis, obstruction, appendicitis, ureteral stone. Gradual onset is characterized by intensification of pain over hours or days; more common in tumors, chronic inflammation, and colon obstruction.

Progression
It is important whether the pain intensifies, decreases, or transitions from intermittent to constant. For example, a perforated ulcer can give severe initial pain that decreases if the perforation closes, while intermittent pain that becomes constant indicates obstruction with a risk of necrosis.

Migration of pain
Movement of pain from the site of origin is typical, for example, for acute appendicitis (from the epigastrium or periumbilical area, pain later moves to the right lower quadrant).

Character of pain
Abdominal pain can be characterized as crampy, dull, or sharp and as constant or intermittent. Crampy pain (colic) follows a pattern of waves that repeat at intervals — it suddenly intensifies to an unbearable peak, then subsides or completely disappears for a time. The most typical examples of colic in medical practice are renal colic and biliary colic. Colicky pain is also associated with mechanical obstruction of the small intestine and, when clearly present, is highly suggestive of that condition. Constant dull or sharp abdominal pain is usually caused by stretching or edema of the wall of a hollow organ. When a hollow organ, such as the gallbladder, becomes distended, which is most often the case due to obstruction of the cystic duct, constant, dull pain occurs. When the gallbladder contracts due to obstruction, the stretching of the gallbladder wall suddenly intensifies, creating crescendo pain (biliary colic), in addition to the already present constant dull pain.
Sharp (stabbing) pain is usually well localized (the patient can point with a finger where it hurts). It is usually sudden and very intense. It often indicates irritation of the peritoneum; it occurs in the late phase of appendicitis in the lower right part of the abdomen when every movement, cough, or pressure on that spot causes "stabbing." Sharp pain like a "knife stab" is also characteristic of ulcer perforation. Dull pain is more difficult to precisely locate. Patients describe it as a feeling of pressure, heaviness, or "squeezing" in the stomach. It usually comes from internal organs, most often as a result of irritation of the capsule of an enlarged liver or spleen, which patients describe as persistent, nagging, dull pain below the right or left rib arch.

Intensity of pain
The intensity of pain in an individual patient can often be assessed by the way the patient physically reacts to it. In somatic pain due to peritonitis, the patient is still, lies motionless with legs bent. In visceral pain, for example in cholecystolithiasis or nephrolithiasis, the patient is restless, changes positions, tries to alleviate the symptoms himself.

Localization
Localization can indicate the origin and pathological basis of pain. Visceral pain is generally poorly localized, in the middle zones of the abdomen; often accompanied by nausea, vomiting, pallor, sweating. Somatic pain is well localized, intensifies with pressure, breathing, and movement; usually without vegetative symptoms [2].

Epidemiology
Abdominal pain is the cause of 5-10% of all visits to emergency medicine clinics.
From 50 to 75% of people older than 65 years with acute abdominal pain require hospitalization, and 1/3 of them require surgical intervention. In patients older than 65 years, compared to younger patients, mortality is 6 to 8 times higher. In 25% of patients who leave the emergency medicine clinic and even 35-41% of patients hospitalized due to abdominal pain, the cause remains undetermined. In 80% of patients with unexplained cause of abdominal pain, the pain usually subsides spontaneously within two weeks from the onset [3].

Pathophysiology
Based on origin, pain can be: nociceptive - tissue damage, neuropathic - nerve damage, and psychogenic - predominantly psychological. Given the multitude of diseases that can manifest with this symptom, accurate interpretation of abdominal pain represents a great challenge for the physician, requiring not only theoretical knowledge but also extensive practical experience. Depending on pathophysiological mechanisms, abdominal pain can be divided into visceral, somatic (parietal), and referred [4]. Sensory pain receptors or nociceptors are located in the mucosa, muscle layers of hollow organs of the gastrointestinal tract (GIT), and mesentery. Nociceptors are peripheral endings of myelinated A delta nerve fibers and unmyelinated C fibers.
Visceral pain arises from stimulation of free nerve endings in visceral organs and is transmitted by slow C fibers originating from the wall of hollow organs, mesentery, and capsule of solid organs. The fibers enter the spinal cord bilaterally and at several levels, so visceral pain is poorly circumscribed. The pain can be dull, sharp, or crampy in character. It does not depend on breathing or body position, but can be characterized by radiation to adjacent parts of the body and the presence of other visceral symptoms such as nausea, vomiting, and loss of appetite. Visceral pain is caused by ischemia, inflammation, or stretching of hollow organs or the capsule of solid organs. The most characteristic visceral pain is colic, which arises from excessive contraction of the muscle of a hollow organ during obstruction (e.g., colic due to stone in the urinary or biliary tract). The moment when dull, diffuse pain transitions into clearly localized pain marks the spread of the pathological process from the visceral to the parietal peritoneum.

Somatic pain is transmitted by fast A fibers to the dorsal ganglia of the spinal cord on the side of the source of the painful stimulus and the corresponding dermatome, so this pain is well circumscribed. By nature, it is sharp and constant, depends on breathing and body position.
It is characteristic that muscle defense and skin hyperesthesia above the affected part of the peritoneum can occur. This is the result of direct irritation of the parietal peritoneum due to ischemia, inflammation, or stretching [5]. Table 1 shows the characteristics of visceral and somatic pain.

Table 1. Comparative characteristics of visceral and somatic pain

Referred pain is well-localized pain that is distant from the affected organ. It is felt in the skin dermatomes of somatic afferent nerves that enter the spinal cord at the same level as the visceral afferent fibers of the affected organ. It is pain felt at a site that is not the actual source of pain. It arises due to shared nerve innervation of the internal organ and the skin.
Practically, the brain "mislocalizes" the pain. Sometimes referred pain can be triggered or intensified by palpation of the affected organ. Pressure on the skin at the site where referred pain is felt usually does not change the intensity of pain [6]. The referral of pain from abdominal organs to other regions is so characteristic that from this referral one can conclude which organ is affected (Table 2).

Table 2. Correlation of localization of referred pain, potential source, and typical diseases

DURATION OF PAIN

Depending on the time course, we distinguish acute, subacute, and chronic pain.
Acute abdominal pain can appear suddenly or develop over days or even weeks (subacute pain). It is usually constant, less often intermittent, with possible worsenings and improvements. It is one of the most common gastrointestinal symptoms and accounts for 5% of all emergency room visits. In 25-50% of patients, the cause of acute abdominal pain cannot be found. The most commonly identified causes are acute appendicitis, intestinal obstruction, diseases of the gallbladder and biliary tract, diseases of the urinary tract, intestinal diverticula, and acute pancreatitis. In women of reproductive age, we must always consider gynecological causes of abdominal pain [7].
We speak of chronic abdominal pain when it lasts at least 6 months. It can be constant or intermittent. Chronic abdominal pain is the reason for 25-50% of all visits to gastroenterology offices. The most common cause of chronic abdominal pain are functional gastrointestinal disorders such as irritable bowel syndrome, functional dyspepsia, and functional biliary pain. Chronic abdominal pain resulting from organic diseases is most often caused by chronic inflammatory bowel diseases, peptic ulcers of the stomach and duodenum, celiac disease, adhesions, chronic inflammation of the pancreas, and neoplasms. Chronic pain associated with defecation occurs in irritable bowel syndrome, chronic postprandial pain in functional dyspepsia and chronic mesenteric ischemia, and chronic pain associated with the menstrual cycle in endometriosis and other gynecological diseases [8].
Functional abdominal pain syndrome belongs to the group of functional gastrointestinal disorders, which are diagnostically defined by the Rome criteria (Roma IV: CAPS - centrally mediated abdominal pain syndrome). Despite extensive
Acute abdomen is a synonym for sudden diseases of abdominal organs, characterized by severe abdominal pain, nausea with or without vomiting, signs of peritoneal irritation, and more or less pronounced general impairment. Due to the urgency of the condition, often only a rough definition of the disease is possible, but not a reliable and final diagnosis. The necessity of therapeutic action thus prevails over a more precise diagnosis. Causes of acute abdominal pain can be surgical or non-surgical (Table 3)

Table 3: Surgical and non-surgical causes of acute abdomen

In the initial assessment of a patient with abdominal pain, it is particularly important to timely recognize potentially life-threatening conditions, as shown in Table 4.

Table 4. Five potentially life-threatening causes of abdominal pain

EVALUATION OF THE PATIENT WITH ABDOMINAL PAIN

History
A thorough history and systematic clinical examination represent the foundation of the diagnostic approach to a patient with abdominal pain and determine the rational choice of laboratory and imaging tests. In a significant number of patients, the diagnosis can be made based on clinical assessment alone, while in a smaller proportion of patients the cause remains unclear despite extensive diagnostics.
Although abdominal pain is most often a consequence of gastrointestinal diseases, extra-abdominal causes (cardiovascular, respiratory, metabolic, urological, and gynecological) should always be considered in the differential diagnosis. Early recognition of life-threatening conditions has particular priority, because the time interval from the appearance of symptoms to adequate therapeutic intervention is directly related to the treatment outcome.

Demographic data (age and sex), comorbidities, previous surgeries and hospitalizations, current therapy, allergies, lifestyle habits, and family history significantly guide differential-diagnostic reasoning.
Analysis of pain must be systematic and include: localization, onset, progression, duration, intensity, character, migration, and irradiation, as well as factors that provoke or alleviate the pain. It is necessary to actively inquire about accompanying symptoms: nausea, vomiting, diarrhea or constipation, weight loss, fever, jaundice, dyspnea, chest pain, palpitations, as well as urogenital complaints. In patients with abdominal pain, it is important to recognize the so-called "Red Flags," i.e., alarm symptoms, which indicate potentially life-threatening conditions and require urgent diagnostics [10]. The significance of alarm symptoms is shown in Table 5.

Table 5. Alarm signs and clinical significance

Special categories of patients require increased clinical caution:

Elderly patients – often have an atypical, sparse, or masked clinical picture.
Women of reproductive age – pregnancy and its complications must be excluded.
Immunocompromised – increased risk of opportunistic infections and malignancies.

Clinical examination
Assessment begins already at the first contact with the patient – general appearance, body position, level of consciousness, and orientation often indicate the severity of the condition. Vital parameters (blood pressure, pulse, respiratory rate, temperature, oxygen saturation) enable rapid assessment of hemodynamic and respiratory stability. In patients with vomiting, diarrhea, fever, or bleeding, assessment of hydration status is necessary.

Abdominal examination includes:
Inspection - Assessment of the shape and symmetry of the abdomen, distension, postoperative scars, skin changes, and visible masses.
Palpation - Performed systematically, starting away from the site of greatest tenderness. Superficial palpation is performed first, then deep palpation. The following are assessed:
- local tenderness
- muscle defense
- rebound tenderness
- presence of palpable masses

Muscle defense represents a sign of irritation of the parietal peritoneum and is most pronounced in perforations of gastroduodenal ulcer (chemical peritonitis). It is milder in inflammatory processes, while in intraperitoneal bleeding it may be discrete. In bleeding into the lumen of the digestive tract, defense is absent.

Percussion - Used to assess free fluid and pneumoperitoneum.
Auscultation - Assessment of peristalsis and possible vascular murmurs.
Rectal examination is an integral part of the evaluation. Gynecological or urological examination is performed as indicated [2].
Typical clinical signs that help in establishing the diagnosis are shown in Table 6, and the localization of the most common causes of abdominal pain in Table 7.

Table 6. Typical clinical signs that help in establishing the diagnosis

Table 7. Most common causes of abdominal pain by localization

Laboratory diagnostics
The basic laboratory panel includes:
- complete blood count with differential
- electrolytes and kidney function
- glycemia
- liver function tests
- amylase and lipase
- inflammation parameters
- urinalysis

Based on clinical indication, the following are determined:
- troponin (suspicion of acute coronary syndrome)
- D-dimer (suspicion of pulmonary embolism)
- blood gases and lactate (suspicion of ischemia or sepsis)
- pregnancy test is mandatory for women of reproductive age

Tumor markers have no role in the initial diagnosis of abdominal pain due to insufficient sensitivity and specificity, but serve for monitoring already diagnosed malignant disease [3].

Imaging diagnostics
The choice of method depends on the clinical suspicion:
- Native abdominal X-ray – pneumoperitoneum, ileus.
- Abdominal ultrasound – pathology of the gallbladder, urinary tract, gynecological diseases, assessment of the abdominal aorta.
- CT abdomen with contrast – perforations, abscesses, malignancies, complicated inflammatory diseases.

In case of suspicion of thoracic etiology, a chest X-ray or echocardiography is indicated.
Endoscopic procedures have a diagnostic, and often therapeutic role.

TREATMENT OF PATIENTS WITH ABDOMINAL PAIN

The Latin saying "Dolorem sedare, medici divinum opus est" emphasizes the basic principle of medical practice – alleviating pain represents not only a therapeutic but also an ethical obligation of the physician.

The therapeutic approach to a patient with acute abdominal pain can be:
- Causal (etiological) – directed at the underlying disease.
- Symptomatic (supportive) – directed at stabilizing vital functions and controlling symptoms.

In urgent conditions, initial stabilization of the patient has priority (principles of the ABC approach), in parallel with diagnostic evaluation.

Supportive treatment
Supportive measures include:
- fluid and electrolyte replacement (oral or parenteral)
- hemodynamic support (vasopressors and inotropes as indicated)
- analgesic therapy
- antiemetic therapy
- oxygen therapy
- correction of metabolic disorders

In case of suspicion of an acute surgical condition, timely consultation with an abdominal surgeon is necessary [11].

Analgesic therapy
Modern data indicate that the use of opioid analgesics in acute abdominal pain does not reduce the diagnostic value of the clinical examination, nor does it negatively affect the treatment outcome. Therefore, adequate analgesia should not be delayed for fear of "masking" the clinical picture.

The choice of analgesic depends on the intensity of pain and the general condition of the patient and may include:
- nonsteroidal anti-inflammatory drugs
- opioids
- spasmolytics
Long-term use of opioids in chronic or functional abdominal pain is not recommended due to the risk of dependence and opioid-induced hyperalgesia.

Treatment of functional pain
In situations where, after adequate diagnostic evaluation, no organic cause of pain is established, a functional or centrally conditioned etiology is considered. In such cases, the following may be indicated:
- psychological or psychiatric evaluation
- use of tricyclic antidepressants (TCA)
- selective serotonin reuptake inhibitors (SSRI)
- serotonin and norepinephrine reuptake inhibitors (SNRI)

These drugs act through modulation of central pain perception, independent of their antidepressant effect [12].

Rational use of antibiotics
Empirical use of antibiotics in patients with abdominal pain must be clearly indicated and based on clinical suspicion of bacterial infection or intra-abdominal inflammatory process. Routine use of antibiotics in undifferentiated abdominal pain is not justified.

Antibiotic therapy is indicated in:
- suspicion of intra-abdominal infection (e.g., perforation of hollow organ, abscess, complicated diverticulitis)
- acute cholangitis
- peritonitis
- septic condition of unclear abdominal origin
- severe forms of pancreatitis with evidence of infection immunocompromised patients with a clinical picture of infection

The choice of antibiotic should cover the most common causes of intra-abdominal infections (Gram-negative enterobacteria, anaerobes), taking into account local resistance patterns and individual risk factors.

Therapy should be:
- timely (especially in case of septic shock),
- adequately dosed,
- time-limited in accordance with clinical response.

Prolonged or inadequate use of antibiotics increases the risk of developing resistance, Clostridioides difficile infection, and other complications, so regular re-evaluation of the need for continued therapy is recommended [13].

Patients at increased risk of unfavorable outcome
Increased morbidity and mortality are expected in:
- patients older than 65 years
- immunocompromised
- polymorbid patients
- patients after abdominal operations or recent endoscopic procedures
- pregnant women (especially in the first trimester)
- patients with sudden onset of severe, constant pain
- patients with signs of peritonitis or hemodynamic instability

Indications for hospitalization
Hospital treatment is indicated in patients with:
- suspicion of peritonitis
- obstruction or perforation of the intestine
- acute intra-abdominal or gastrointestinal bleeding
- hemodynamic instability
- uncontrolled pain despite adequate oral therapy
- need for parenteral therapy or invasive supportive measures [14]

CONCLUSION

A patient with abdominal pain represents a diagnostic challenge that requires a systematic, rational, and time-efficient approach due to the extensive differential diagnosis, which includes both harmless pathological processes and many that threaten life. The foundation of the evaluation is a carefully taken history and a detailed clinical examination, which guide further laboratory and imaging diagnostics. Early recognition of life-threatening conditions, adequate risk assessment, and timely consultation with a surgeon or attending physician are of crucial importance for the treatment outcome.
Monitoring and treatment of patients with functional gastrointestinal diseases today represents an increasing challenge. Supportive measures and analgesia should not be delayed, while etiological therapy is carried out purposefully, in accordance with the established and probable diagnosis.
Rational use of antibiotics and avoidance of unnecessary therapy represent an important part of modern clinical practice. By integrating clinical experience, diagnostic tools, and a multidisciplinary approach, it is possible to optimize the management of patients and reduce morbidity and mortality associated with abdominal pain.

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