What is volvulus

A volvulus is a twisting of a loop of intestine around itself and the mesentery that supports it, causing impairment of the blood supply or can result in complete or partial bowel obstruction ¹. A volvulus causes a blockage that may cut off blood flow. Part of the intestine may be damaged as a result. The term volvulus is Latin for “volvere,” which means “to roll.”

Volvulus symptoms include abdominal bloating, pain, vomiting, constipation, and bloody stools. The onset of symptoms may be gradual or rapid. The mesentery becomes so tightly twisted that blood supply is cut off, resulting in an ischemic bowel. Pain may be significant and fever may develop.

Risk factors for volvulus include a birth defect known as intestinal malrotation, Hirschsprung disease, an enlarged colon, pregnancy, and abdominal adhesions. A high fiber diet and chronic constipation also increase the risk. In adults, the sigmoid colon and cecum are most affected. In children, the small intestine and stomach are more commonly involved. Diagnosis is typically made with medical imaging such as plain X-rays, CT scan, or a GI series.

Initial treatment for sigmoid volvulus may be with sigmoidoscopy or a barium enema. Due to the high risk of recurrence, a bowel resection within two days is generally recommended. If the bowel is severely twisted or the blood supply is cut off, emergent surgery is required. In a cecal volvulus, part of the bowel is usually removed. If the cecum is still healthy, it may be returned and sutured in place.

Sigmoid and cecal volvulus most often occurs between the ages of 30 and 70.

• Volvulus occurs more frequently in middle-aged and elderly men.
• Volvulus arises as a rare complication in patients with a redundant colon, a normal anatomic variation resulting in extra-colonic loops.
• Sigmoid volvulus is a very common form of volvulus and is responsible for 8% of all intestinal obstructions. Sigmoid volvulus is particularly common in constipated and elderly persons. Patients experience pain, distension, and constipation.
• Cecal volvulus is less common than sigmoid volvulus and is associated with pain and small bowel obstruction.
• Midgut volvulus typically occurs in babies that are predisposed because of congenital intestinal malrotation.
• Segmental volvulus occurs in people of any age, usually with a predisposition because of abnormal intestinal contents or adhesions.
• Volvulus of the cecum, transverse colon, or sigmoid colon usually occurs in adults with minor predisposing factors such as redundant intestinal tissue and constipation.

Cases of volvulus occur commonly in Africa, the Middle East, and India, presumably because of a high-fiber diet. Rates of volvulus in the United States are about 2 to 3 per 100,000 people per year. Outcomes are related to whether bowel tissue is ischemic or necrotic.

Colonic volvulus

Volvulus usually affects the colon. Colonic volvulus is a rare occurrence in the United States, attributing to approximately 4% of causes of large bowel obstruction, followed by cancer and diverticulitis ². Of note, there are certain regions of the world where colonic volvulus happens more frequently. In areas of the Middle East, India, South America, Africa, and Russia, colonic volvulus attributes for approximately 50% of all accounts of colonic obstruction. The regional areas listed above have been coined the “volvulus belt.” Sigmoid volvulus occurs more frequently compared to cecal volvulus ³.

United States

Colonic volvulus ranks below cancer and diverticulitis as a cause of large-bowel obstruction.

• Colonic volvulus causes make up approximately 5% of intestinal obstruction.
• Colonic volvulus causes constitute 10% to 15% of all cases of large-bowel obstruction. The most common location of large-bowel torsion is the sigmoid colon (80%), the cecum (15%), transverse colon (3%), and splenic flexure (2%).

International

In Africa and the Middle East, nearly 50% of large-bowel obstructions are caused by volvulus, usually of the sigmoid colon.

Colonic volvulus causes

Associated risk factors for colonic volvulus are advanced age, chronic constipation, and diets rich in high fiber ². Cecal volvulus most commonly occurs in the second and third decade of life, compared to sigmoid volvulus that occurs in the seventh and eighth decade of life. Patients that have psychiatric conditions or are institutionalized and taking psychotropic drugs have a higher incidence of colonic volvulus. The use of psychotropic drugs can cause hindered intestinal mobility and predispose patients to volvuluses ¹.

Colonic volvulus signs and symptoms

Patients with colonic volvulus may present with an intestinal obstruction. Often, the symptoms are hard to differentiate from blockages caused by colon cancers. Common symptoms are acute onset of severe abdominal pain, constipation, obstipation, nausea, and vomiting. Often, a tympanitic and markedly distended abdomen are seen, and often, the distention is more impressive than other causes of bowel obstruction. When the wall of the distended bowel is placed under increased tension, the cecal volvulus may be associated with ischemia. Another cause of ischemia may be occlusion of the arterial blood supply to the mesentery cause by torsion. Ominous signs include tachycardia, rebound tenderness, and severe abdominal pain not improved with medical management.

Colonic volvulus diagnosis

Work up for a colonic volvulus includes a complete blood count (CBC) with differential, a comprehensive metabolic panel, and a lactic acid. Laboratory findings may be useful; however, they are not diagnostic. A leukocytosis level, a left shift (pandemic), or a metabolic acidosis may indicate systemic sepsis, bowel ischemia, or peritoneal infection. Electrolyte abnormalities may develop in the setting of a bowel obstruction and vomiting.

Abdominal plain x-rays may be confirmatory for a volvulus, especially if a “bent inner tube” or a “coffee bean” sign are seen. These refer to the appearance of the air-filled closed loop of the colon which forms the volvulus. A barium enema is used to demonstrate a “bird’s beak” at the point where the segment of proximal bowel and distal bowel rotate to form the obstructing volvulus. This area will show an acute and sharp tapering that has the appearance of a bird’s beak. If a perforation is suspected, barium should be avoided due to its potentially lethal effects when distributed throughout the free intraperitoneal cavity. Gastrografin, which is safer, can be substituted for barium.

In approximately 80% of colonic obstructions, a carcinoma invading the wall of the intestine is found to be the cause of the obstruction. This is usually easily diagnosed with CT scan and endoscopic biopsies.

Cecal volvulus

In cecal volvulus, the terminal ileum and right colon are involved. Cecal volvulus describes torsion of the cecum around its mesentery which often results in obstruction. If unrecognized, it can result in bowel perforation and fecal peritonitis. When a volvulus involves the cecum alone, it is also called a cecal bascule ². This occurs when a highly mobile cecum traverses from a caudad to cephalad direction ⁴. Cecal volvulus is less common than sigmoid volvulus, accounting for 10% to 15% of all cases of volvulus, and it tends to affect women in the sixth decade of life.

There are two predisposing factors that are important for the development of a cecal volvulus:

1. a developmental failure of peritoneal fixation allows the proximal colon to be free and mobile: this occurs in 11-25% of the population
2. restriction of the bowel at a fixed point within the abdomen, acting as a fulcrum for rotation, e.g. adhesion, abdominal mass, scarring from calcified lymph nodes

Medical history of these patients may include prior abdominal surgery, the presence of a pelvic mass, violent coughing, atonia of the colon, extreme exertion, unpressurised air travel, or third-trimester pregnancy.

In general, there are three different types of cecal volvulus ²:

• Type 1: This cecal volvulus forms by a clockwise axial twisting or torsion of the cecum along the long axis. The location of the cecal volvulus is in the right lower quadrant.
• Type 2: This cecal volvulus develops from a twisting or torsion of a portion of the cecum and a portion of the terminal ileum. The location of the cecum gets displaced to an ectopic location (typically left upper quadrant) and is relocated in an inverted orientation. Traditionally, but not for all cases, a type 2 cecal volvulus will encounter a counterclockwise twist.
• Type 3: This cecal volvulus (also known as cecal bascule) is the upward folding of the cecum. There is no axial twisting like with type 1 and type 2.

Type 1 and type 2 cecal volvulus, which involve axial torsion, account for approximately 80% of all cecal volvuli. Cecal bascules account for the remaining 20% of cecal volvuli ².

There are no evidence-based studies on the diagnosis or treatment of cecal volvulus ². Cecal volvulus is not so common in North America but since it carries a very high mortality, it is important that healthcare workers be aware of the disorder.

Colonoscopic decompression may be appropriate if patient unfit for surgery. However, laparotomy is normally required. Where there is colonic ischemia, a right hemicolectomy is performed; in some cases, the primary anastomosis is not possible, and stoma formation at both ends is the safest option.

If the cecum is viable and the volvulus reduces, there are a number of options:

• reduction alone, but this is associated with the highest risk of recurrence
• right hemicolectomy
• cecostomy
• cecopexy

Figure 1. Cecal volvulus

Footnote: Abdominal xray of a cecal volvulus revealing a dramatic dilation of bowel extending from the right lower quadrant moving upwards to the left upper quadrant of the abdomen.

Cecal volvulus pathology

In ~50% of the patients, the cecum twists in the axial plane, rotating clockwise or counter-clockwise around its long axis and appearing in the right lower quadrant.

The other half of patients have what is known as the loop type of cecal volvulus, in which the cecum both twists and inverts, occupying the left upper quadrant of the abdomen. The terminal ileum is usually twisted along with the cecum. Visualization of a gas-filled appendix confirms the diagnosis.

There is a variant of cecal volvulus termed a “cecal bascule” that occurs when the cecum folds anteriorly without any torsion. A cecal bascule is often seen as a dilated loop in the mid-abdomen and although there is an association with prior surgery, adhesions and bands they are not essential for a volvulus to occur. In 10% of the population, there is a deficient peritoneal fixation of the cecum and ascending colon allowing abnormal mobility. Depending on the length of the mobile segment of right colon a variety of obstructive bowel patterns may result.

Cecal volvulus signs and symptoms

Cecal volvulus presents with clinical features of proximal large bowel obstruction. This is usually with colicky abdominal pain, vomiting, and abdominal distension.

Cecal volvulus diagnosis

Radiographic imaging can help differentiate between a sigmoid and cecal volvulus from other abdominal pathologies. For a cecal volvulus, an abdominal x-ray will reveal a dramatic dilation of bowel extending from the right lower quadrant moving upwards to the left upper quadrant of the abdomen. Usually, a patient with a cecal volvulus will present with small and large bowel obstructions, with the collapse of the distal large bowel, and with extensive dilation of the proximal small bowel. A definitive sign of a cecal volvulus is the upward displacement of the appendix with obstruction of the large bowel. Comparatively, a sigmoid volvulus will show findings of a bent inner tube sign with the apex of the volvulus located in the left upper quadrant.

Abdominal plain films are sufficient to make the diagnosis of a sigmoid volvulus; however, abdominal x-rays are less diagnostic for a cecal volvulus. Thus, the additional imaging of a CT scan can help differentiate the approximate location of torsion. An abdominopelvic CT scan is diagnostic for a cecal volvulus in approximately 90% of the patients. About 10% of the time, patients are diagnosed with a cecal volvulus intraoperatively ⁵.

A mesentery torsion around the ileocolic vessels as seen on a CT scan is described as a “whirl sign” and is considered pathognomonic for diagnosis of a cecal volvulus.

Cecal volvulus treatment

Treatment for cecal volvuli usually entails a surgical intervention. Other inventions such as a barium enema or a colonoscopy, can offer a non-operative reduction of a cecal volvulus. However, these modalities are rarely successful. For these non-operative treatments, there is a high risk of perforations and should not be attempted. Colonic necrosis can be miss up to approximately 20% to 25% of the time when non-operative modalities are used. Surgical treatment and will vary based on patient stability and findings seen intraoperatively. Intraoperatively, the surgeon will ascertain if there is bowel compromise or if the bowel is viable. These findings will help dictate appropriate surgical intervention ⁶.

For patients who are stable with no bowel compromise, an ileocolic resection or a right hemicolectomy should be performed. In patients that receive an ileocolic resection, an additional colopexy to tack the right remnant colon to the posterior peritoneum to minimize the recurrence of another volvulus.

For patients who are hemodynamically unstable without bowel compromise, a cecopexy should be performed in conjunction with a cecostomy tube placement or cecopexy can be done alone.

For patients who are stable with bowel, the surgeon should proceed with a right hemicolectomy or ileocolic resection followed by an ileocolic anastomosis.

For patients who are unstable with bowel, the surgeon should proceed with a right hemicolectomy or ileocolic resection with an ileostomy creation. Later, once the patient is stabilized, the ileostomy may be reversed.

Common complications after cecal volvulus treatment include:

• Wound infection
• Sepsis
• Anastomotic leak
• Colocutaneous fistula
• Pelvic or abdominal abscess

Postoperative and rehabilitation care

Patients often require a prolonged stay in the hospital. Most patients are elderly and frail. If the ileus is prolonged, they often require IV fluids for a few days. DVT prophylaxis and physical therapy are recommended.

Cecal volvulus prognosis

Cecal volvulus is not a benign disorder. If the treatment is delayed, it carries a mortality in excess of 30%. Most studies indicate that the time to treat should be within 24-72 hours after diagnosis. This much time is required for hydration and any investigations. Even after cecal volvulus is treated, patients have high morbidity due to a prolonged ileus, wound infection, respiratory failure, and bowel obstruction ⁷.

There are only small case series and isolated reports on outcomes of patients managed with cecal volvulus. For those who have delayed diagnosis, the outcomes are poor. Even those who undergo timely surgery have high morbidity as a consequence of their age. Laparoscopic surgery is preferred to open surgery but sometimes the urgency of the situation may not allow it. No matter how one approaches the patient, the family must be fully informed of the potential complications, including recurrence and a stoma ⁸.

Sigmoid volvulus

Sigmoid volvulus is an abnormal twisting of the sigmoid colon along its mesenteric axis that causes closed-loop obstruction and can lead to ischemia, perforation, and death. Sigmoid volvulus is the most common type of volvulus of the colon ⁹. Large bowel volvulus accounts for ~5% of all large bowel obstructions, with ~60% of intestinal volvulus involving the sigmoid colon ¹⁰. Sigmoid volvulus is more common in the elderly ¹¹. Less common are caecal volvulus and volvulus of the transverse colon. Sigmoid volvulus presents most commonly in patients who are less mobile, bed bound and institutionalized, usually with a background of chronic constipation.

Sigmoid volvulus is more common in Africa, as the food intake is of high fiber and the base of the sigmoid mesentery in the African population is narrow compared with other ethnic groups, leading to an anatomical situation that makes the population more susceptible to developing a sigmoid volvulus.

In order for a volvulus to occur, the bowel needs to be able to twist around a narrow-based mesentery. This occurs mostly in less mobile patients with a history of chronic constipation, where the sigmoid colon becomes chronically distended and redundant ⁹.

Figure 2. Sigmoid volvulus

Footnote: 85 year old male with one day of distension and progressive diffuse abdominal pain. Constipation but no fever or vomiting.

Sigmoid volvulus causes

There is a wide range of sigmoid volvulus causes; some are geographically-specific ¹³:

• Chronic constipation and/or laxative abuse
• Fiber-rich diet (especially in Africa)
• Chagas disease (especially in South America)

Associations

• chronic neurological conditions (e.g. Parkinson disease, multiple sclerosis, pseudobulbar palsy)
• medications from chronic psychiatric conditions (e.g. chronic schizophrenia)

Pathophysiology

Volvulus is a classical example of a large bowel closed loop obstruction. If inflow and outflow of the colon are both obstructed, the obstructed bowel will continue to distend, due to a large amount of gas forming bacteria trapped inside. This will eventually lead to a perforation of the obstructed segment.

While the colon is obstructed and distending, there is impaired blood supply, leading to ischemia, as well as bacterial translocation of the gut flora. Usually, the venous outflow is compromised first, increasing congestion even further, until arterial supply stops. The colonic mucosa is most susceptible to ischaemic insult, leading to an impaired barrier and translocation of bacteria, until the ischemia affects muscular and serosa, leading to necrosis and perforation.

Sigmoid volvulus can become a recurrent situation, and in those patients treated conservatively, the base of mesentery will eventually become fibrotic and the bowel chronically distended.

Sigmoid volvulus signs and symptoms

Patients presenting with volvulus are usually of an older age group with potential other comorbidities, often have reduced mobility or are bed bound and commonly get referred from residential and nursing homes. A history of chronic constipation is common. The symptoms usually leading to acute hospital admission are a loss of appetite and reduced oral intake, increasing abdominal distension, and cessation of bowel output. Patients complain of discomfort due to the significant distension, but are rarely in pain, unless ischemia and/or a perforation have occurred. They can, however, have respiratory compromise due to the splinting of the diaphragm that is a result of the colonic distension.

Patients may present with sigmoid volvulus as a recurrent problem if they have been treated with conservative measures in the past. A recurrent episode of volvulus needs to be taken a seriously as a first presentation and requires the same attention to history and physical examination as a patient presenting with volvulus for the first time.

Examination of the abdomen reveals significant distension, a generalized tympanitic percussion note and potentially guarding and rebound over areas of ischemia or impending perforation. If a perforation has already occurred, the patient will be grossly peritonitic. Digital rectal examination reveals an empty and often capacious rectum.

Sigmoid volvulus diagnosis

The patient should have the standard blood work (full blood count and renal function tests), to aid in resuscitation and assess the kidney function for a potential CT scan with contrast. Plain abdominal radiographs will show the classical coffee bean or kidney bean sign, and often dilatation of the proximal colon. Depending on the duration of symptoms, the proximal colon can decompress into the distal small bowel, as long as the ileocaecal valve is incompetent. CT scan shows the characteristic “whirl” appearance of the twisted mesentery, as well as the distended loop of sigmoid colon with an air-fluid level. Free air on either the abdominal radiograph or the CT scan indicates a more serious bowel perforation and requires immediate action.

A CT scan is recommended to establish the diagnosis and distinguish the etiology from other causes of large bowel obstruction, such as a malignant tumor. This is especially the case if the patients present with symptoms for the first time and have not had any previous colonic investigations such as a colonoscopy.

Sigmoid volvulus treatment

Rectal tube insertion is successful in treating 90% of cases ¹³. The mortality rate is 20-25% ¹¹. The most serious complication is bowel ischemia.

Before any surgical intervention, the patient needs to be adequately resuscitated with intravenous fluids, and electrolyte imbalances should be corrected. A nasogastric tube can aid proximal decompression. Decompression of the sigmoid volvulus should be attempted with a soft rectal flatus tube by the bedside, ideally feeding the tube under direct vision through a rigid sigmoidoscope. Flexible Sigmoidoscopy with gentle insufflation is indicated if the bedside decompression fails or if there are concerns about the viability of the bowel wall, as the mucosa can be inspected during the sigmoidoscopy and areas of mucosal ischemia will become obvious.

Bedside decompression with a flatus tube should only be carried out by experienced physicians, and under no circumstance against resistance, as there is a risk of inadvertent iatrogenic perforation. The safest method to decompress the sigmoid colon is under direct vision with rigid or flexible sigmoidoscopy.

A successful decompression will immediately result in the evacuation of liquid and gas per rectum with subsequent resolution of the abdominal distension, resulting in a soft abdomen.

This resolution can be documented on a repeat abdominal radiograph.

It is important to assess the patient for sustained resolution once the flatus tube has been removed and the patient is started on oral intake, to avoid the volvulus recur before the patient is even discharged.

Those patients who cannot be decompressed or who have progressed to compromised viability of the colon will need surgical intervention. The surgery of choice is a sigmoid colectomy with either a primary anastomosis or an end colostomy, depending on findings during the surgery and the individual patients’ physiological reserves.

A patient presenting with bowel perforation will require aggressive resuscitation and an immediate laparotomy to control the fecal contamination and remove the perforated segment of bowel.

Patients presenting with recurrent episodes of sigmoid volvulus that can be decompressed should have an informed discussion about the benefits and risks of an elective resection of the sigmoid to prevent further episodes of volvulus leading to emergency admission to hospital. In the elective situation, a sigmoid colectomy can usually be performed with a primary anastomosis instead of an end colostomy, unless the patient has significant comorbidities.

Gastric volvulus

Gastric volvulus is a rare, clinical event that occurs in both adults and pediatric patients. A gastric volvulus occurs when the stomach rotates on itself at least 180 degrees along its transverse or longitudinal axis ¹⁴. It should be at least 180° and cause bowel obstruction to be called gastric volvulus. Merely gastric rotation on its root is not considered gastric volvulus.

Gastric volvulus occurs in children usually less than 1 year of age and occurs in older adults, those who are older than 50 years. There does not seem to a predilection for gastric volvulus for either gender or race. The most common cause of a gastric volvulus in both children and adults is a paraesophageal hernia.

Organo-axial volvulus is more common in adults, responsible for 60% of presentations. Mesentero-axial volvulus is more common in children.

Gastric strangulation is a complication that can occur after the development of acute gastric volvulus. Gastric volvulus causes a foregut obstruction in the patients. Gastric volvulus may present either acutely, or it may present with intermittent, recurrent, and chronic symptoms. When the stomach twist on itself there is always a risk for stomach strangulation with necrosis, perforation, and shock. The mortality for an acute volvulus can range from 30% to 50%, thus highlighting the importance of early diagnosis and treatment of gastric volvulus.

Timely diagnosis and treatment of acute gastric volvulus can potentially decrease morbidity and mortality. Patients can simply present with mild abdominal pain associated with nausea and vomiting, without emesis. Other patients can present with sepsis from necrosis of their volvulus and similar chief complaints.

Surgical repair, including stomach detorsion and gastropexy, is the main treatment modality for gastric volvulus. Detorsion may be performed open or laparoscopically. If the stomach is strangulated or necrotic, gastric resection may be required.

Figure 3. Gastric volvulus (organoaxial volvulus)

Footnote: 4 year old boy presented with acute abdominal pain, tenderness and dyspnea. The stomach twists along its own longitudinal axis giving rise to organoaxial volvulus. Organoaxial volvulus is the most common gastric volvulus and occurs secondary to diaphragmatic trauma or paraesophageal hernia. When the stomach twists along its longitudinal axis the esophago-gastric junction lies below the pyloro-duodenal junction.

Gastric volvulus subtypes

Both subtypes are surgical emergencies.

Organo-axial volvulus

• more common of the two types in adults (2/3 of cases)
• commonly occurs in the setting of trauma or para-esophageal hernia
• stomach is rotated along its long axis (along the cardiopyloric line, which is drawn between the cardia and the pylorus)
• mirror image of normal anatomy can occur with reversal of the greater and lesser curves
• antrum rotates anterosuperiorly
• fundus rotates posteroinferiorly
• complete (>180º) present with obstruction or ischemia
• incomplete rotation (<180º) also called organo-axial position of the stomach, usually asymptomatic

Mesentero-axial volvulus

• less common in adults, but is more common than organo-axial volvulus in the pediatric population (59% of gastric volvulus)
• rotation around short axis from the lesser to greater curvature (i.e. perpendicular to the cardiopyloric line)
• usually incomplete, <180°
• displacement of antrum above gastro-esophageal junction; stomach appears upside-down with the antrum and pylorus superior to the fundus and proximal body
• coincides with the axis of mesenteric attachment and is associated with severe obstruction and strangulation
• less associated with diaphragmatic defect
• plain films may show an intrathoracic stomach with two air fluid levels ¹⁶

Gastric volvulus causes

In 10% to 30% of cases, gastric volvulus is considered primary and results from laxity and disruption of the stomach’s ligamentous attachments (gastrohepatic, gastrocolic, gastrolienal, and gastrophrenic). For the majority of cases, gastric volvulus is caused by a gastric, splenic, or diaphragmatic anatomic disorder, the most common being a diaphragmatic hernia or an abnormality in gastric function. The organoaxial rotation of the stomach as described by Singleton is the most common gastric volvulus (two-thirds of cases) and occurs when the stomach rotates around the pylorus and the gastroesophageal (GE) junction. Mesenteroaxial rotation is less common (one-third of cases), and occurs when the stomach rotates longitudinal line parallel to the gastrohepatic omentum.

Associations

• wandering spleen ¹⁷
• congenital diaphragmatic hernia
• diaphragmatic eventration
• laparoscopic adjustable gastric banding ¹⁸

Gastric volvulus signs and symptoms

Patients may present with the classic triad of Borchardt:

• severe sudden epigastric pain
• intractable retching without vomiting
• inability to pass a nasogastric tube

Chronic symptoms are more common in patients with mesentero-axial volvulus.

A patient’s clinical presentation depends on the speed of onset, the type of stomach rotation (volvulus), and the completeness of the foregut obstruction. The presentation of an acute gastric volvulus can be quite severe with acute epigastric abdominal pain associated with severe retching. In 1904, Borchardt described the triad of acute epigastric pain, retching with the inability to vomit, and the difficulty or inability to pass a nasogastric tube. This triad occurs in up to 70% of patients who present with an acute organoaxial volvulus. The nasogastric tube passes easily in patients who present with an acute mesenteroaxial volvulus, as the lower esophageal sphincter remains open. The opposite is appreciated with organoaxial volvulus, as the nasogastric tube is more difficult to pass, due to the involvement of more proximal structures including the lower esophageal sphincter, the fundus, or the cardia. Patients who present with chronic, intermittent, and vague signs and symptoms of upper abdominal pain, nausea, dysphagia, early satiety vomiting, and hiccups may have a chronic partial or intermittent gastric volvulus.

Gastric volvulus diagnosis

The diagnosis of a gastric volvulus can be suspected with a good history and physical exam; however, diagnosis can be difficult. The diagnosis of a gastric volvulus may be confirmed radiologically when patients are symptomatic. Plain chest x-ray films that are suspicious for a gastric volvulus are those that demonstrate a spherical stomach or a double air-fluid level on upright chest films and the retrocardiac air-fluid level above the diaphragm on lateral chest film. Albas et al. described 4 radiologic findings predictive for a gastric volvulus on an upper gastrointestinal (GI) contrast study by showing gastric air-fluid level above the diaphragm, a paucity of distal bowel gas, reversal of the relative position of the greater curvature of the stomach, and a downward pointing pylorus. A barium swallow may be helpful as an adjunct to chest x-ray. Computed tomography (CT) scans of the chest, abdomen, and pelvis can also be diagnostic. CT scan of the chest, abdomen, and pelvis can provide information about the nature of volvulus, and other intraabdominal organs that may be involved, thus assisting pre-operative planning.

Gastric volvulus treatment

The traditional treatment for a patient presenting with an acute gastric volvulus has been an immediate operation reducing and untwisting the volvulus. This remains the gold standard; however, attempted medical management may be useful in patients that are a very high risk for surgery. Immediate surgical resection is required for necrosis or perforation of the stomach. Simultaneously, the diaphragmatic hernia should be reduced and closed. The stomach is then fixed to the anterior abdominal wall with suture, or by the placement of a gastrostomy tube. Open surgery, or the combination of laparoscopic and endoscopic surgical techniques, have good results. Laparoscopy, when used to repair chronic and intermittent gastric volvulus, is often be less morbid than an open operation. Patients who are fit enough to undergo a surgical procedure should proceed to have their chronic gastric volvulus repaired because of the high morbidity and mortality (30% to 50%) associated with strangulated gastric volvulus.

Good results have also been reported with conservative treatment of an acute gastric volvulus in elderly patients if they are not presenting in extremis. Conservative treatment has also been used to help patients with intermittent and chronic volvulus. The patient should be kept sitting upright, and a nasogastric tube should be gently inserted to decompress the stomach. The patient should be adequately resuscitated and re-evaluated often. Some high-risk, elderly patients can be treated endoscopically with decompression and reduction of the stomach, and placement of a percutaneous gastrostomy tube to gastropexy the stomach to the abdominal wall. Percutaneous gastrostomy placement can be done as an adjunct in ill patients with chronic or intermittent volvulus, or that may have other critical issues that need to be handled before definitive surgery, for example, sepsis from another source.

Midgut volvulus

A midgut volvulus of malrotated bowel can potentially occur at any age but in approximately 75% of cases occur within a month of birth ¹⁹. Most of these are within the first week ²⁰, with 90% occuring within 1 year ²¹. Typically the infant is entirely normal for a period before suddenly presenting with bilious vomiting. If the midgut volvulus does not spontaneously reduce, then the venous obstruction created by the superior mesenteric vein wrapped around the superior mesenteric artery results in venous obstruction and gradual onset of ischemia and eventual necrosis. As this occurs, the abdomen becomes swollen as fluid accumulates in the lumen of the bowel, and becomes tender. Eventually, peritonitis and shock become established.

Midgut volvulus occurs as a complication of intestinal malrotation. A midgut volvulus is usually part of a vascular compromise in the intestinal mesentery in intestinal malrotation. Anomalies of rotation and fixation are twice as common in males as in females ²². They are classified as non-rotation, incomplete rotation, reverse rotation, and anomalous fixation of the mesentery.

A small portion patients that present with malrotation will demonstrate chronic obstructive symptoms. These symptoms may result from Ladd bands across the duodenum or, occasionally, from intermittent volvulus. Symptoms include intermittent abdominal pain and intermittent vomiting, which may occasionally be bilious. Infants with malrotation may demonstrate a failure to thrive, and they may be diagnosed initially as having gastroesophageal reflux disease (GERD).

Urgent surgical repair (Ladd procedure) is required to prevent ischemia or to resect infarcted bowel loops. If resection is performed stomas are usually created. Additionally, the Ladd bands are divided and the mesenteric pedicle widened. In some instances, pexy (surgical fixation) of the duodenum and cecum may be performed although it is unclear if this is of benefit in preventing recurrence ²³. It should be noted that normal anatomical positioning is not achieved; the duodenum and small bowel remain on the right, and the cecum and colon are on the left side of the abdomen ²³.

Figure 4. Midgut volvulus

Footnote: 6 weeks old infant with bilious vomiting and abdominal pain. Contrast has been administered via a nasogastric tube to a child. It passes from the stomach into the duodenum. Contrast demonstrates a malplaced duodenojejunal flexure and a corkscrew appearance of the jejunum. This confirms both malrotation and volvulus. The duodenojejunal flexure should usually be located to the left of midline at the level of the duodenal cap. Here it is not, indicating that there is malrotation. The lumen is narrowed and passes directly inferiorly in a corkscrew pattern. Findings are of midgut volvulus secondary to intestinal malrotation.

Midgut volvulus causes

During fetal development, the intestines develop as three portions. These are foregut, midgut, and hindgut. The midgut portion of the intestines undergoes normal rotation during the four weeks and six weeks of gestation. The fetal midgut intestines develop so rapidly that the abdominal cavity cannot house the all the intestines. Therefore, a portion of intestines herniates into the umbilical cord. The intestines herniate back into the abdominal cavity with a 270-degree counter-clockwise rotation around the bloody supply to midgut, the superior mesenteric artery. The fourth portion of the duodenum and proximal jejunum of the intestines acquires a C-loop, with the development of the ligament of Treitz, and is superior to the superior mesenteric artery. The cecal portion of the intestine becomes fixed to the retroperitoneum, superior to the superior mesenteric artery, in a diagonal axis at approximately the level of the T12 vertebra to the level of the right of the L5 vertebra.

Genetic mutations likely disrupt the signaling critical for normal intestinal rotation. For instance, mutations in the gene BCL6 leading to the absence of left-sided expression of its transcript result in malrotation. In an incomplete rotation, the cecum remains in the epigastrium, and the fibrotic band forms from the duodenum to the retroperitoneum as the cecum continues to form. The band, also knowns as Ladd’s bands, crosses over the duodenum, connecting the cecum to the lateral abdominal wall. The Ladd’s band creates a potential point of obstruction.

The mesenteric takeoff is then confined to the epigastrium leading to a narrow pedicle, constricting all the branches of the superior mesenteric artery that supplies the midgut. A volvulus can occur around the mesentery which then obstructs the proximal jejunum and causes ischemia to the midgut. Obstruction and bowel ischemia can then ensue if the problem is not promptly corrected surgically.

Associations

These include ²⁵:

• gastroschisis
• omphalocele
• diaphragmatic hernia
• duodenal or jejunal atresia

Midgut volvulus signs and symptoms

Midgut volvulus can happen at any age, but most commonly occurs during the first few weeks of life. Bilious emesis is usually the first sign of volvulus. Infants that present with bilious vomiting, acute duodenal obstruction, or abdominal tenderness associated with hemodynamic deterioration must be rapidly evaluated to ensure that they do not have intestinal malrotation along with volvulus, as this should raise particular suspicions for this diagnosis. If left untreated, vascular compromise of the midgut initially causes bloody stools but eventually results in circulatory collapse. Physical exam findings for the advanced disease will show signs of peritonitis suggestive of intestinal ischemia with erythema and edema of the abdominal wall which will lead to shock and death if left untreated. An index of suspicion for this condition must be high, as the abdominal signs are minimal early in the disease process. Plain abdominal x-rays show a paucity of gas throughout the intestine with a few scattered air-fluid levels. When these findings are present, the patient should undergo immediate fluid resuscitation to ensure adequate perfusion and urine output followed by prompt exploratory laparotomy. In cases where the child is stable, consider laparoscopy.

In older children and adults, abdominal pain is the most common symptom and may present with abrupt onset over hours or days or as chronic intermittent pain over weeks, months, or years. Intermittent vomiting, chronic diarrhea, malabsorption, or failure to thrive comprises other potential presenting symptoms.

Midgut volvulus diagnosis

The patient may not always appear ill, and the plain films may suggest partial duodenal obstruction. Upper gastrointestinal series that shows incomplete rotation with the duodenojejunal junction displaced to the right is the best indication of obstruction. The duodenum may show a corkscrew effect diagnosing volvulus or complete duodenal obstruction, with the small bowel looping entirely on the right side of the abdomen. A barium enema may show a displaced cecum, but this sign is unreliable, especially in a small infant in whom the cecum is normally in a somewhat higher position than in an older child.

Midgut volvulus treatment

When volvulus is suspected, early surgical intervention is mandatory if the ischemic process is to be prevented or reversed. Volvulus occurs clockwise and is therefore untwisted counterclockwise; which one can remember with the phrase “turning back the hands of time.”

Follow by a Ladd procedure, named after William Edward Ladd, the pediatrician who first performed the procedure in 1936. This operation does not correct the malrotation but instead helps to open the narrow mesenteric pedicle to prevent volvulus from recurring. The Ladd procedure is performed by lysing the band formed between the cecum and the lateral abdominal wall as well as duodenum and terminal ileum, which allows the superior mesenteric artery to relax. This maneuver allows the duodenum to relax into the right lower quadrant and the cecum into the left lower quadrant; these structures do not need to be secured with a suture. An appendectomy (removal of the appendix) is also done to circumvent errors in the event patient has diagnostic imaging.

When a patient presents with advanced ischemia, a simple reduction of the volvulus without the Ladd procedure should be performed followed by a “second-look” laparotomy which is performed 24 to 36 hours later to evaluate the vascular integrity of the small intestines.

A transparent plastic silo may be placed to facilitate constant evaluation of the intestine and to plan for the timing of re-exploration. If a necrotic bowel is present, then the surgeon can conservatively resect it to ensure adequate length for feeding and prevention of short-gut syndrome. With early diagnosis and correction, the prognosis is excellent. Delay can lead to mortality or short-gut syndrome requiring intestinal transplantation.

Midgut volvulus prognosis

Prognosis is dependent on the state of the small bowel and presence of systemic shock. In cases where no ischemia of the bowel is present, and the child is otherwise well, the prognosis is extremely good. Overall a mortality of 3-9% is reported ²³.

Small bowel obstruction for adhesions is seen a distant complication in 5-10% of cases.

Volvulus causes

Volvulus occurs when redundant and loose mesentery twist around an axis. Volvulus is associated with intestinal malrotation, an enlarged colon, a long mesentery, Hirschsprung disease, pregnancy, abdominal adhesions, and chronic constipation. In adults, the sigmoid colon is most affected, with the cecum being second most affected. In children, the small intestine is more commonly involved.

Volvulus is typically caused by two mechanisms:

1. chronic constipation and
2. a high-fiber diet

In both the instances, the sigmoid colon becomes dilated and heavy making it susceptible to torsion. With repeated attacks of torsion, the mesentery shortens. The chronic inflammation leads to the formation of adhesions which then entrap the sigmoid colon into fixed twisted position.

In cecal volvulus, the predominant symptom is small bowel obstruction (nausea, vomiting, and lack of flatus), because the obstructing point is close to the ileocecal valve and small intestine.

In sigmoid volvulus, although pain may be present, constipation may be more prominent.

Volvulus causes severe pain with an accumulation of gas and fluid in the portion of the bowel obstructed resulting in necrosis of the affected intestinal wall, acidosis, and death. This is known as a closed loop obstruction. Acute volvulus requires immediate surgical intervention to untwist the affected segment of bowel.

Volvulus may occur in patients with Duchenne muscular dystrophy due to the smooth muscle dysfunction.

Volvulus symptoms

Patients with volvulus are usually debilitated and bedridden. Many of these individuals have a history of neuropsychiatry dysfunction, and thus, a medical history is usually unavailable.

Signs and symptoms of volvulus include pain, bloating, vomiting, constipation, bloody stool, fever, and significant pain when the abdomen is palpated. Depending on the duration of the condition, there may be signs of peritonitis and bleeding per rectum. The severe abdominal distension can also compromise respiration in some patients.

Volvulus complications

Complications of volvulus include gangrene, strangulation, perforation fecal peritonitis, and recurrent volvulus.

Volvulus diagnosis

Diagnosis usually is made by taking a thorough history and performing a physical examination; it is confirmed by radiographic studies. The diagnosis of colonic volvulus usually is included in the differential diagnosis which also includes bowel obstruction, mesenteric ischemia, and malignancy.

Abdominal plain x-rays may be confirmatory for a volvulus, especially if a “bent inner tube” or a “coffee bean” sign are seen. These refer to the appearance of the air-filled closed loop of the colon which forms the volvulus. A barium enema is used to demonstrate a “bird’s beak” at the point where the segment of proximal bowel and distal bowel rotate to form the obstructing volvulus. This area will show an acute and sharp tapering that has the appearance of a bird’s beak. If a perforation is suspected, barium should be avoided due to its potentially lethal effects when distributed throughout the free intraperitoneal cavity. Gastrografin, which is safer, can be substituted for barium.

In approximately 80% of colonic obstructions, a carcinoma invading the wall of the intestine is found to be the cause of the obstruction. This is usually easily diagnosed with CT scan and endoscopic biopsies.

Volvulus treatment

Initial treatment for sigmoid volvulus is sigmoidoscopy or a barium enema. Due to a high recurrence rate, a bowel resection within two days is recommended. In a cecal volvulus, part of the bowel often needs to be removed.

Treatment for sigmoid volvulus includes sigmoidoscopy. If the mucosa of the sigmoid looks normal, place a rectal tube for decompression, correct electrolytes, ensure adequate fluids, and optimize cardiac, renal and pulmonary abnormalities. The patient should then be taken for surgical repair. If surgery is not performed, there is a high rate of recurrence of volvulus and obstruction. For patients with signs of sepsis or an acute abdominal catastrophe, immediate surgery and resection are advised. In a cecal volvulus, the cecum may be returned to a normal position and then sutured in place via a procedure known as cecopexy. If the bowel is obviously necrotic, then resection with an ileostomy or a colostomy is necessary.

Volvulus surgery

Over the years many surgical techniques have been developed to treat cecal and sigmoid volvulus. In general, conservative procedures where the bowel is adhered with sutures are often associated with higher recurrence rates compared to procedures that involve resection of the bowel. Whether to do the surgery via an open or laparoscopic method depends on surgeon preference and experience. Elderly patients may benefit from minimally invasive procedures.

Volvulus prognosis

Delay in diagnosis and treatment of volvulus is associated with a high morbidity and mortality. The mortality is 30% to 40% in patients in whom treatment of cecal volvulus is delayed.

The recommended interval between endoscopic decompression and surgical intervention is 48 to 72 hours. This allows time for investigation, resuscitation, and intervention to reduce surgical risk ¹.

• Even when volvulus is successfully treated with endoscopic decompression and surgical resection, mortality is still 12% to 15%.
• 50% of patients who undergo endoscopic decompression alone experience recurrence.
• Endoscopic decompression alone for sigmoid volvulus carries a recurrence rate of 40% to 50% and a mortality of 25% to 30% after surgical treatment of the recurrence.

1. Bhimji SS, Cooper W. Volvulus. [Updated 2018 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441836[↩][↩][↩]
2. Le CK, Qaja E. Cecal Volvulus. [Updated 2018 Nov 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470305[↩][↩][↩][↩][↩][↩][↩]
3. Kaushal-Deep SM, Anees A, Khan S, Khan MA, Lodhi M. Primary cecal pathologies presenting as acute abdomen and critical appraisal of their current management strategies in emergency settings with review of literature. Int J Crit Illn Inj Sci. 2018 Apr-Jun;8(2):90-99.[↩]
4. Lung BE, Yelika SB, Murthy AS, Gachabayov M, Denoya P. Cecal bascule: a systematic review of the literature. Tech Coloproctol. 2018 Feb;22(2):75-80.[↩]
5. Dane B, Hindman N, Johnson E, Rosenkrantz AB. Utility of CT Findings in the Diagnosis of Cecal Volvulus. AJR Am J Roentgenol. 2017 Oct;209(4):762-766.[↩]
6. Miura da Costa K, Saxena AK. A systematic review of the management and outcomes of cecal and appendiceal volvulus in children. Acta Paediatr. 2018 Dec;107(12):2054-2058.[↩]
7. Gomes CA, Soares C, Catena F, Di Saverio S, Sartelli M, Gomes CC, Gomes FC. Laparoscopic Management of Mobile Cecum. JSLS. 2016 Oct-Dec;20, 4.[↩]
8. Ramírez-Ramírez MM, Villanueva-Sáenz E, Ramírez-Wiella-Schwuchow G. [Elective laparoscopic right colectomy for caecal volvulus: case report and literature review]. Cir Cir. 2017 Jan – Feb;85(1):87-92.[↩]
9. Lieske B, Antunes C. Sigmoid Volvulus. [Updated 2018 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441925[↩][↩]
10. Vandendries C, Jullès MC, Boulay-Coletta I et-al. Diagnosis of colonic volvulus: findings on multidetector CT with three-dimensional reconstructions. Br J Radiol. 2010;83 (995): 983-90. doi:10.1259/bjr/35714052[↩]
11. Brant WE, Helms CA. Fundamentals of Diagnostic Radiology. Lippincott Williams & Wilkins. (2007) ISBN:0781761352.[↩][↩]
12. Sigmoid volvulus. https://radiopaedia.org/cases/sigmoid-volvulus-6?lang=us[↩]
13. Salati U, Mcneill G, Torreggiani WC. The coffee bean sign in sigmoid volvulus. Radiology. 2011;258 (2): 651-2. doi:10.1148/radiol.101882[↩][↩]
14. Lopez PP, Megha R. Gastric Volvulus. [Updated 2018 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507886[↩]
15. Gastric volvulus. https://radiopaedia.org/cases/gastric-volvulus-3?lang=us[↩]
16. Menuck L. Plain film findings of gastric volvulus herniating into the chest. AJR Am J Roentgenol. 1976;126 (6): 1169-74.[↩]
17. Liu HT, Lau KK. Wandering spleen: an unusual association with gastric volvulus. AJR Am J Roentgenol. 2007;188 (4): W328-30. doi:10.2214/AJR.05.0672[↩]
18. Kicska G, Levine MS, Raper SE et-al. Gastric volvulus after laparoscopic adjustable gastric banding for morbid obesity. AJR Am J Roentgenol. 2007;189 (6): 1469-72. doi:10.2214/AJR.05.1547[↩]
19. Peterson CM, Anderson JS, Hara AK et-al. Volvulus of the gastrointestinal tract: appearances at multimodality imaging. Radiographics. 29 (5): 1281-93. doi:10.1148/rg.295095011[↩]
20. Devos AS, Blickman JG, Blickman JG. Radiological Imaging of the Digestive Tract in Infants and Children. Springer Verlag. (2007) ISBN:3540407332.[↩]
21. Fischer JE, Bland KI. Mastery of surgery. Lippincott Williams & Wilkins. (2007) ISBN:078177165X[↩]
22. Coste AH, Bhimji SS. Midgut Volvulus. [Updated 2018 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441962[↩]
23. Fischer JE, Bland KI. Mastery of surgery. Lippincott Williams & Wilkins. (2007) ISBN:078177165X.[↩][↩][↩]
24. Midgut volvulus. https://radiopaedia.org/cases/midgut-volvulus?lang=us[↩]
25. Weissleder R, Wittenberg J, Harisinghani MG et-al. Primer of diagnostic imaging. Mosby Inc. (2007) ISBN:0323040683.[↩]

What is leukocytosis

Leukocytosis is an increase in the number of white blood cells to more than 11,000 cells per mm³ (11.0 × 10⁹ per L) of blood in nonpregnant adults ¹. Leukocytosis in the range of approximately 50,000 to 100,000 per mm³ (50.0 to 100.0 × 10⁹ per L) is sometimes referred to as a leukemoid reaction. This level of elevation can occur in some severe infections, such as Clostridium difficile infection, sepsis, organ rejection, or in patients with solid tumors ². Leukocytosis greater than 100,000 per mm³ is almost always caused by leukemias or myeloproliferative disorders ³. Leukocytes are white blood cells that exist in the blood, the lymphatic system, and tissues and are an important part of your body’s defense system. Leukocytes help protect you against infections and they have a role in inflammation, allergic responses, and protection against cancer. The white blood cell (WBC) count totals the number of leukocytes in a person’s sample of blood. It is one test among several that is included in a complete blood count (CBC), which is often used in the general evaluation of a person’s health.

If you have had your spleen removed, you may have a persistent mild to moderate increase in white blood cell (WBC) count.

Intense exercise or severe emotional or physical stress can cause leukocytosis, but the white blood cell (WBC) count is not used to evaluate these conditions. Pregnancy in the final month and labor may also be associated with leukocytosis.

In the U.S. population, white blood cell (WBC) counts are related to one’s age, sex, ethnicity, and smoking status. It is not uncommon for the elderly to fail to develop leukocytosis as a response to infection.

There are many drugs that cause both increased and decreased white blood cell (WBC) counts.

Blood is made up of a few different types of cells suspended in fluid called plasma. In addition to leukocytes (white blood cells), there are red blood cells and platelets. All of these blood cells are produced in your bone marrow and subsequently released into the blood to circulate. There are five types of leukocytes, and each has a different function.

Three types of leukocytes are referred to as “granulocytes” because of the granules present in their cytoplasm. These granules release chemicals and other substances as part of the immune response. Granulocytes include neutrophils, which normally make up the largest number of circulating leukocytes, eosinophils, and basophils. The other two types of leukocytes are monocytes and lymphocytes. Lymphocytes are further divided into three subtypes: B lymphocytes that produce antibodies (also known as immunoglobulins), T lymphocytes, and natural killer cells (NK cells).

When there is an infection or an inflammatory process somewhere in your body, the bone marrow produces more leukocytes, releasing them into the blood, and through a complex process, they move to the site of infection or inflammation. As the condition resolves, the production of leukocytes by the bone marrow subsides and the number of leukocytes drops to normal levels again.

In addition to infections and inflammation, there are a number of conditions that can affect the production of leukocytes by the bone marrow or the survival of leukocytes in the blood, such as cancer or an immune disorder, resulting in either increased or decreased numbers of leukocytes in the blood. The white blood cell count, along with the other components of the complete blood count (CBC), alerts a health practitioner to possible health issues. Results are often interpreted in conjunction with additional tests such as a white blood cell differential and a blood smear review. A differential may inform the health practitioner as to which type of leukocyte may be low or high, and a blood smear can reveal the presence of abnormal and/or immature populations of leukocyte.

If results indicate a problem, a wide variety of other tests maybe performed in order to help determine the cause. A health practitioner will typically consider an individual’s signs and symptoms, medical history, and results of a physical examination to decide what other tests may be necessary. For example, as needed, a bone marrow biopsy will be performed to evaluate the bone marrow status.

Figure 1. Leukocytes (white blood cells)

Types of leukocytes

All leukocytes have nuclei, which distinguishes them from the other blood cells, the anucleated red blood cells and platelets (Figure 1). Leukocytes differ in size, the nature of their cytoplasm, the shape of the nucleus, and their staining characteristics, and they are named for these distinctions. Two pairs of broadest categories classify them either by structure (granulocytes or agranulocytes) or by cell division lineage (myeloid cells or lymphoid cells) (see Figure 3). These broadest categories can be further divided into the five main types: neutrophils, eosinophils, basophils, lymphocytes, and monocytes ⁴. These types are distinguished by their physical and functional characteristics. Monocytes and neutrophils are phagocytic. Further subtypes can be classified; for example, among lymphocytes, there are B cells, T cells, and NK (natural killer) cells.

Normally, five types of leukocytes are in circulating blood. For example, leukocytes with granular cytoplasm are called granulocytes, whereas those without cytoplasmic granules are called agranulocytes (see Figure. 3).

A typical granulocyte is about twice the size of a red blood cell. Members of this group include neutrophils, eosinophils, and basophils. Granulocytes develop in red bone marrow as do red blood cells, but they have short life spans, averaging about 12 hours.

Neutrophils have fine cytoplasmic granules that appear light purple in neutral stain. The nucleus of an older neutrophil is lobed and consists of two to five sections (segments, so these cells are sometimes called segs) connected by thin strands of chromatin (Figure 4). Younger neutrophils are also called bands because their nuclei are C-shaped. Neutrophils account for 54% to 62% of the leukocytes in a typical blood sample from an adult.

Eosinophils contain coarse, uniformly sized cytoplasmic granules that appear deep red in acid stain (Figure 4). The nucleus usually has only two lobes (termed
bilobed). Eosinophils make up 1% to 3% of the total number of circulating leukocytes.

Basophils are similar to eosinophils in size and in the shape of their nuclei, but they have fewer, more irregularly shaped cytoplasmic granules that appear deep
blue in basic stain (Figure 4). Basophils usually account for less than 1% of the circulating leukocytes.

The leukocytes of the agranulocyte group include monocytes and lymphocytes. Monocytes generally arise from red bone marrow. Lymphocytes are formed in the organs of the lymphatic system, as well as in the red bone marrow.

Monocytes, the largest blood cells, are two to three times greater in diameter than red blood cells. Their nuclei are round, kidney-shaped, oval, or lobed. They usually make up 3% to 9% of the leukocytes in a blood sample and live for several weeks or even months.

Lymphocytes are only slightly larger than red blood cells. A typical lymphocyte has a large, round nucleus surrounded by a thin rim of cytoplasm. These cells account for 25% to 33% of circulating leukocytes. Lymphocytes may live for years.

Blood composition

Note: Blood is a complex mixture of formed elements in a liquid extracellular matrix, called blood plasma. Note that water and proteins account for 99% of the blood plasma.

Note: Blood consists of a liquid portion called plasma and a solid portion (the formed elements) that includes red blood cells, white blood cells, and platelets. When blood components are separated by centrifugation, the white blood cells and platelets form a thin layer, called the “buffy coat,” between the plasma and the red blood cells, which accounts for about 1% of the total blood volume. Blood cells and platelets can be seen under a light microscope when a blood sample is smeared onto a glass slide.

Normal Leukocyte Life Cycle and Responses

The life cycle of leukocytes includes development and differentiation, storage in the bone marrow, margination within the vascular spaces, and migration to tissues. Stem cells in the bone marrow produce cell lines of erythroblasts, which become red blood cells; megakaryoblasts, which become platelets; lymphoblasts; and myeloblasts. Lymphoblasts develop into various types of T and B cell lymphocytes. Myeloblasts further differentiate into monocytes and granulocytes, a designation that includes neutrophils, basophils, and eosinophils (Figure 2 and 3). Once white blood cells have matured within the bone marrow, 80% to 90% remain in storage in the bone marrow. This large reserve allows for a rapid increase in the circulating white blood cell count within hours. A relatively small pool (2% to 3%) of leukocytes circulate freely in the peripheral blood ²; the rest stay deposited along the margins of blood vessel walls or in the spleen. Leukocytes spend most of their life span in storage. Once a leukocyte is released into circulation and peripheral tissues, its life span ranges from two to 16 days, depending on the type of cell.

Figure 2. Bone marrow anatomy

Footnote: Anatomy of the bone. The bone is made up of compact bone, spongy bone, and bone marrow. Compact bone makes up the outer layer of the bone. Spongy bone is found mostly at the ends of bones and contains red marrow. Bone marrow is found in the center of most bones and has many blood vessels. There are two types of bone marrow: red and yellow. Red marrow contains blood stem cells that can become red blood cells, white blood cells, or platelets. Yellow marrow is made mostly of fat.

Figure 3. White blood cells development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell

Figure 4. White blood cells development

Leukocytosis normal range

The normal range for white blood cell (WBC) counts changes with age and pregnancy (Table 1) ⁵. Healthy newborn infants may have a white blood cell (WBC) count from 13,000 to 38,000 per mm³ (13.0 to 38.0 × 10⁹ per L) at 12 hours of life ¹. By two weeks of age, this decreases to approximately 5,000 to 20,000 per mm³ (5.0 to 20.0 × 10⁹ per L), and gradually declines throughout childhood to reach adult levels of 4,500 to 11,000 per mm³ (4.5 to 11.0 × 10⁹ per L) by about 21 years of age ⁵. There is also a shift from relative lymphocyte to neutrophil predominance from early childhood to the teenage years and adulthood ⁶. During pregnancy, there is a gradual increase in the normal white blood cell (WBC) count (third trimester 95% upper limit = 13,200 per mm³ [13.2 × 109 per L] and 99% upper limit = 15,900 per mm3 [15.9 × 109 per L]), and a slight shift toward an increased percentage of neutrophils ⁷. In one study of afebrile postpartum patients, the mean white blood cell (WBC) count was 12,620 per mm3 (12.62 × 109 per L) for women after vaginal deliveries and 12,710 per mm3 (12.71 × 10⁹ per L) after cesarean deliveries. Of note, positive bacterial cultures were not associated with leukocytosis or neutrophilia, making leukocytosis an unreliable discriminator in deciding which postpartum patients require antibiotic therapy ⁸. Patients of black African descent tend to have a lower white blood cell (WBC) count (by 1,000 per mm³ [1.0 × 10⁹ per L]) and lower absolute neutrophil counts ⁹.

Table 1. White Blood Cell Count Variation with Age and Pregnancy

Differentiation by Type of White Blood Cell

Changes in the normal distribution of types of white blood cells (WBCs) can indicate specific causes of leukocytosis (Table 2) ¹⁰. Although the differential of the major types of white blood cells (WBCs) is important for evaluating the cause of leukocytosis, it is sometimes helpful to think in terms of absolute, rather than relative, leukopenias and leukocytoses. To calculate the absolute cell count, the total leukocyte count is multiplied by the differential percentage. For example, with a normal white blood cell (WBC) count of 10,000 per mm³ (10.0 × 10⁹ per L) and an elevated monocyte percentage of 12, the absolute monocyte count is 12% or 0.12 times the white blood cell (WBC) count of 10,000 per mm³, yielding 1,200 per mm³ (1.2 × 10⁹ per L), which is abnormally elevated.

Table 2. Normal White Blood Cell Distribution

Leukocytosis causes

Leukocytosis, an increase in the number of white blood cells to more than 11,000 cells per microliter (11.0 × 10⁹ per L) of blood, is often caused by the normal response of the body to help fight an infection, or to some drugs such as corticosteroids. However, an increase in the number of white blood cells is also caused by cancers of the bone marrow (such as leukemia) or by the release of immature or abnormal white blood cells from the bone marrow into the blood.

The most common type of leukocytosis is neutrophilia (an increase in the absolute number of mature neutrophils to greater than 7,000 per mm³ [7.0 × 10⁹ per L]), which can arise from infections, stressful conditions, chronic inflammation, medication use, and other causes (see Table 3 below) ². Lymphocytosis (when lymphocytes make up more than 40% of the white blood cell (WBC) count or the absolute count is greater than 4,500 per mm3 [4.5 × 10⁹ per L]) can occur in patients with pertussis, syphilis, viral infections, hypersensitivity reactions, and certain subtypes of leukemia or lymphoma. Lymphocytosis is more likely to be benign in children than in adults ⁶. Epstein-Barr virus infection, tuberculosis or fungal disease, autoimmune disease, splenectomy, protozoan or rickettsial infections, and malignancy can cause monocytosis (monocytes make up more than 8% of the white blood cell (WBC) count or the absolute count is greater than 880 per mm³ [0.88 × 10⁹ per L]) ¹⁰.

Table 3. Nonmalignant Causes of Neutrophilia

Footnote: After patient characteristics, causes are listed in approximate order of frequency.

Abbreviations: CRP = C-reactive protein; WBC = white blood cell.

Eosinophilia (eosinophil absolute count greater than 500 per mm³ [0.5 × 10⁹ per L]), although uncommon, may suggest allergic conditions such as asthma, urticaria, atopic dermatitis or eosinophilic esophagitis, drug reactions, dermatologic conditions, malignancies, connective tissue disease, idiopathic hypereosinophilic syndrome, or parasitic infections, including helminths (tissue parasites more than gut-lumen parasites) ¹¹. Isolated basophilia (number of basophils greater than 100 per mm³ [0.1 × 10⁹ per L]) is rare and unlikely to cause leukocytosis in isolation, but it can occur with allergic or inflammatory conditions and chronic myelogenous leukemia (Table 4) ¹².

Table 4. Selected Conditions Associated with Elevations in Certain White Blood Cell Types

Nonmalignant causes

A reactive leukocytosis, typically in the range of 11,000 to 30,000 per mm³ (11.0 to 30.0 × 10⁹ per L), can arise from a variety of etiologies. Any source of stress can cause a catecholamine-induced demargination of white blood cells, as well as increased release from the bone marrow storage pool. Examples include surgery, exercise, trauma, burns, and emotional stress ¹³. One study showed an average increase in white blood cells of 2,770 per mm³ (2.77 × 10⁹ per L) peaking on postoperative day 2 after knee or hip arthroplasty ¹⁴. Medications known to increase the white blood cell (WBC) count include corticosteroids, lithium, colony-stimulating factors, beta agonists, and epinephrine. During the recovery phase after hemorrhage or hemolysis, a rebound leukocytosis can occur.

Leukocytosis is one of the hallmarks of infection. In the acute stage of many bacterial infections, there are primarily mature and immature neutrophils; sometimes, as the infection progresses, there is a shift to lymphocyte predominance. The release of less-mature bands and metamyelocytes into the peripheral circulation results in the so-called “left shift” in the white blood cell (WBC) differential. Of note, some bacterial infections paradoxically cause neutropenias, such as typhoid fever, rickettsial infections, brucellosis, and dengue ¹⁵. Viral infections may cause leukocytosis early in their course, but a sustained leukocytosis is not typical, except for the lymphocytosis in some childhood viral infections.

An elevated white blood cell (WBC) count is a suggestive, but not definitive, marker of the presence of significant infection. For example, the sensitivity and specificity of an elevated white blood cell (WBC) count in diagnosing acute appendicitis are 62% and 75%, respectively ¹⁶. For diagnosing serious bacterial infections without a source in febrile children, the discriminatory value of leukocytosis is less than that of other biomarkers, such as C-reactive protein or procalcitonin ¹⁷. Although a white blood cell (WBC) count greater than 12,000 per mm³ (12.0 × 10⁹ per L) is one of the criteria for the systemic inflammatory response syndrome (or sepsis when there is a known infection), leukocytosis alone is a poor predictor of bacteremia and not an indication for obtaining blood cultures ¹⁸.

Other acquired causes of leukocytosis include functional asplenia (predominantly lymphocytosis), smoking, and obesity. Patients with a chronic inflammatory condition, such as rheumatoid arthritis, inflammatory bowel disease, or a granulomatous disease, may also exhibit leukocytosis. Genetic causes include hereditary or chronic idiopathic neutrophilia and Down syndrome.

Malignant causes

Leukocytosis may herald a malignant disorder, such as an acute or chronic leukemia or a myeloproliferative disorder, such as polycythemia vera, myelofibrosis, or essential thrombocytosis ¹⁹. Many solid tumors may lead to a leukocytosis in the leukemoid range, either through bone marrow involvement or production of granulocyte colony-stimulating or granulocyte-macrophage colony-stimulating factors ²⁰. Chronic leukemias are most commonly diagnosed after incidental findings of leukocytosis on complete blood counts in asymptomatic patients. Patients with features suggestive of hematologic malignancies require prompt referral to a hematologist/oncologist (Table 5) ²¹.

Table 5. Findings Suggestive of Hematologic Malignancies in the Setting of Leukocytosis

Leukocytosis diagnosis

A systematic approach to patients with leukocytosis includes identifying historical clues that suggest potential causes (Figure 5). Fever and pain may accompany infections or malignancies; other constitutional symptoms, such as fatigue, night sweats, weight loss, easy bruising, or bleeding, might suggest malignancy ²¹. Previous diagnoses or comorbid conditions that cause chronic inflammation should be noted, as well as recent stressful events, medication use, smoking status, and history of splenectomy or sickle cell anemia. A history of an elevated white blood cell (WBC) count is important, because duration will help determine the likely cause. Leukocytosis lasting hours to days has a different differential diagnosis (e.g., infections, acute leukemias, stress reactions) than a case that persists for weeks to months (e.g., chronic inflammation, some malignancies).

The physical examination should note erythema, swelling, or lung findings suggestive of an infection; murmurs suggestive of infective endocarditis; lymphadenopathy suggestive of a lymphoproliferative disorder; or splenomegaly suggestive of chronic myelogenous leukemia or a myeloproliferative disorder; petechiae or ecchymoses; or painful, inflamed joints suggestive of connective tissue disease or infection.

Initial laboratory evaluation should include`a repeat complete blood count to confirm the elevated white blood cell (WBC) level, with differential cell counts and a review of a peripheral blood smear. The peripheral smear should be examined for toxic granulations (suggestive of inflammation), platelet clumps (which may be misinterpreted as white blood cells), the presence of immature cells, and uniformity of the white blood cells. On evaluation of a leukocytosis with lymphocyte predominance, a monomorphic population is concerning for chronic lymphocytic leukemia, whereas a pleomorphic (varying sizes and shapes) lymphocytosis is suggestive of a reactive process ²². With all forms of leukocytosis, concurrent abnormalities in other cell counts (erythrocytes or platelets) suggest a primary bone marrow process and should prompt hematology/oncology evaluation.

As indicated by the history and examination findings, physicians should consider performing cultures of blood, urine, and joint or body fluid aspirates; rheumatology studies; a test for heterophile antibodies (mononucleosis spot test); and serologic titers. Radiologic studies may include chest radiography (to identify infections, some malignancies, and some granulomatous diseases) and, as indicated by history, computed tomography or bone scan. If hematologic malignancy is suspected, additional confirmatory testing may include flow cytometry, cytogenetic testing, or molecular testing of the bone marrow or peripheral blood.

If your have leukocytosis, the other tests might your doctor might order include:

Other general tests to check your health may include a comprehensive metabolic panel (CMP). Depending on your signs, symptoms, medical history, physical exam and suspected condition, your healthcare provider may choose to order a variety of other tests. A few general examples include:

• Bacterial infection: a culture of the affected area (e.g., urine culture, sputum culture, blood culture), strep test
• Viral infection: tests for mononucleosis, EBV
• Inflammation: CRP, ESR
• Autoimmune diseases: ANA
• Allergies: Allergy tests
• Leukemia: Bone marrow biopsy, immunophenotyping (e.g., flow cytometry), chromosome analysis

Figure 5. Algorithm for the evaluation of leukocytosis

Abbreviations: ANA = antinuclear antibodies; CRP = C-reactive protein; ESR = erythrocyte sedimentation rate

Leukocytosis symptoms

A white blood cell (WBC) count is normally ordered as part of the complete blood count (CBC), which may be performed when an individual undergoes a routine health examination. The test may be done when someone has general signs and symptoms of an infection and/or inflammation such as:

• Fever, chills
• Body aches, pain
• Headache
• A variety of other signs and symptoms, depending on the site of suspected infection or inflammation

Testing may be performed when there are signs and symptoms that a health practitioner thinks may be related to a blood disorder, autoimmune disorder, or an immune deficiency.

A white blood cell (WBC) may be ordered often and on a regular basis to monitor an individual who has been diagnosed with an infection, blood or immune disorder or another condition affecting white blood cells (WBCs). It may also been ordered periodically to monitor the effectiveness of treatment or when a particular therapy is known to affect white blood cells (WBCs), such as radiation or chemotherapy.

Leukocytosis treatment

Once the cause of your leukocytosis is found, your doctor can recommend ways to treat it. In most cases, treatment for leukocytosis is not necessary.

In extreme instances of hyperleukocytosis syndrome (e.g., acute leukemia), leukapheresis, hydration, and urine alkalinization to facilitate uric acid excretion are indicated; however, perform these treatments only in consultation with a hematologist, oncologist, or both. Direct treatment toward the underlying etiology.

Leukemic hyperleukocytosis may cause clinically significant complications when the WBC count exceeds 100,000/μL in acute myelogenous leukemia and 300,000/μL in acute lymphoblastic leukemia. Therefore, in patients with these findings, measures to reduce the WBC count are advisable. However, a decrease in leukocyte count that is too rapid carries a risk of severe tumor lysis syndrome and should be avoided.

Leukapheresis or exchange blood transfusion is a treatment of choice for this purpose, with hydration, urine alkalinization, and administration of allopurinol or rasburicase (uric acid oxydase) to reduce serum uric acid and minimize tumor lysis syndrome. When rasburicase is used, urine alkalinization is not recommended.

A study by Nguyen et al. ²³ indicated that supportive care and conservative management can discourage early hyperleukocytosis-related morbidity and mortality in children with acute lymphoblastic leukemia, possibly negating the need for leukapheresis. A study by Choi et al. ²⁴, meanwhile, found no evidence that in patients with acute leukemia (myelogenous or lymphoblastic) and hyperleukocytosis, leukapheresis improves early mortality rates or reduces the incidence of either tumor lysis syndrome or disseminated intravascular coagulopathy.

Promptly institute definitive treatment with appropriate chemotherapy. A study by Mamez et al. ²⁵ indicated that the administration of oral hydroxyurea before chemotherapy can lower the rate of early death in hyperleukocytic patients with acute myelogenous leukemia. The study, which involved 160 patients, found the hospital mortality rate for patients who received pre-chemotherapy hydroxyurea to be 19%, compared with 34% for those who received no hydroxyurea prior to chemotherapy. However, the two treatment groups did not differ with regard to disease-free survival.

1. Evaluation of Patients with Leukocytosis. Am Fam Physician. 2015 Dec 1;92(11):1004-1011. https://www.aafp.org/afp/2015/1201/p1004.html[↩][↩][↩][↩][↩][↩]
2. Cerny J, Rosmarin AG. Why does my patient have leukocytosis? Hematol Oncol Clin North Am. 2012;26(2):303–319, viii.[↩][↩][↩]
3. Jain R, Bansal D, Marwaha RK. Hyperleukocytosis: emergency management. Indian J Pediatr. 2013;80(2):144–148.[↩]
4. LaFleur-Brooks, M. (2008). Exploring Medical Language: A Student-Directed Approach (7th ed.). St. Louis, Missouri, US: Mosby Elsevier. p. 398. ISBN 978-0-323-04950-4.[↩]
5. Hoffman R, Benz EJ Jr, Silberstein LE, Heslop H, Weitz J, Anastasi J. Hematology: Basic Principles and Practice. 6th ed. Philadelphia, Pa.: Elsevier/Saunders; 2013:table 164–20.[↩][↩][↩]
6. Chabot-Richards DS, George TI. Leukocytosis. Int J Lab Hematol. 2014;36(3):279–288.[↩][↩]
7. Lurie S, Rahamim E, Piper I, Golan A, Sadan O. Total and differential leukocyte counts percentiles in normal pregnancy. Eur J Obstet Gynecol Reprod Biol. 2008;136(1):16–19.[↩]
8. Dior UP, Kogan L, Elchalal U, et al. Leukocyte blood count during early puerperium and its relation to puerperal infection. J Matern Fetal Neonatal Med. 2014;27(1):18–23.[↩]
9. Lim EM, Cembrowski G, Cembrowski M, Clarke G. Race-specific WBC and neutrophil count reference intervals. Int J Lab Hematol. 2010;32(6 pt 2):590–597.[↩]
10. Berliner N. Leukocytosis and leukopenia. In: Goldman L, Schafer AI, eds. Goldman’s Cecil Medicine. 24th ed. Philadelphia, Pa.: Elsevier/Saunders; 2012.[↩][↩][↩]
11. Ustianowski A, Zumla A. Eosinophilia in the returning traveler. Infect Dis Clin North Am. 2012;26(3):781–789.[↩]
12. Munker R. Leukocytosis, leukopenia, and other reactive changes of myelopoiesis. In: Munker R, Hiller E, Glass J, Paquette R, eds. Modern Hematology: Biology and Clinical Management. 2nd ed. Totowa, N.J.; Humana Press; 2007.[↩]
13. Iskandar JW, Griffeth B, Sapra M, Singh K, Giugale JM. Panic-attack-induced transient leukocytosis in a healthy male: a case report. Gen Hosp Psychiatry. 2011;33(3):302.e11–302.e12[↩]
14. Deirmengian GK, Zmistowski B, Jacovides C, O’Neil J, Parvizi J. Leukocytosis is common after total hip and knee arthroplasty. Clin Orthop Relat Res. 2011;469(11):3031–3036[↩]
15. Potts JA, Rothman AL. Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations. Trop Med Int Health. 2008;13(11):1328–1340.[↩]
16. Yu CW, Juan LI, Wu MH, Shen CJ, Wu JY, Lee CC. Systematic review and meta-analysis of the diagnostic accuracy of procalcitonin, C-reactive protein and white blood cell count for suspected acute appendicitis. Br J Surg. 2013;100(3):322–329.[↩]
17. Yo CH, Hsieh PS, Lee SH, et al. Comparison of the test characteristics of procalcitonin to C-reactive protein and leukocytosis for the detection of serious bacterial infections in children presenting with fever without source: a systematic review and meta-analysis. Ann Emerg Med. 2012;60(5):591–600.[↩]
18. Dellinger RP, Levy MM, Rhodes A, et al.; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580–637.[↩]
19. Davis AS, Viera AJ, Mead MD. Leukemia: an overview for primary care. Am Fam Physician. 2014;89(9):731–738.[↩]
20. Granger JM, Kontoyiannis DP. Etiology and outcome of extreme leukocytosis in 758 nonhematologic cancer patients: a retrospective, single-institution study. Cancer. 2009;115(17):3919–3923.[↩]
21. Racil Z, Buresova L, Brejcha M, et al. Clinical and laboratory features of leukemias at the time of diagnosis: an analysis of 1,004 consecutive patients. Am J Hematol. 2011;86(9):800–803.[↩][↩]
22. George TI. Malignant or benign leukocytosis. Hematology Am Soc Hematol Educ Program. 2012;2012:475–484.[↩]
23. Nguyen R, Jeha S, Zhou Y, et al. The Role of Leukapheresis in the Current Management of Hyperleukocytosis in Newly Diagnosed Childhood Acute Lymphoblastic Leukemia. Pediatr Blood Cancer. 2016 May 17.[↩]
24. Choi MH, Choe YH, Park Y, et al. The effect of therapeutic leukapheresis on early complications and outcomes in patients with acute leukemia and hyperleukocytosis: a propensity score-matched study. Transfusion. 2018 Jan. 58 (1):208-16 [↩]
25. Mamez AC, Raffoux E, Chevret S, et al. Pre-treatment with oral hydroxyurea prior to intensive chemotherapy improves early survival of patients with high hyperleukocytosis in acute myeloid leukemia. Leuk Lymphoma. 2016 Feb 5. 1-8.[↩]