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Pancreas:Anatomy and Physiology

The pancreas is a glandular retroperitoneal organ that  weight 70-80 gm secretes digestive enzymes (internal secretions) and hormones (external secretions). In humans, the pancreas is a yellowish organ about 7 inches (17.8 cm) long and 1.5 inches. (3.8 cm) wide. The pancreas is divided in to head, neck, body and tail.

Under a microscope, stained sections of the pancreas reveal two different types of parenchyma tissue lightly staining clusters of cells are called islets of Langerhans, which produce hormones that underlie the endocrine functions of the pancreas. Darker staining cells form acini connected to ducts. Acinar cells belong to the exocrine pancreas and secrete digestive enzymes into the gut via a system of ducts. Pancreas is both an endocrine and an exocrine gland, in that it functions to both produce endocrinic hormones released into the circulatory system (such as insulin, and glucagon), primarily to control glucose metabolism, and also secretes digestive/exocrinic pancreatic juice which is secreted eventually via the pancreatic duct into duodenum. Digestive or exocrine function of pancreas is as significant to the maintenance of health as its endocrine function.

Two population of cells in the pancreatic parenchyma make up its digestive enzymes:

Ductal cells: Mainly responsible for production of bicarbonate (HCO3), which acts to neutralize the acidity of the stomach chyme entering duodenum through the pylorus.

Acinar cells: Mainly responsible for production of the inactivate pancreatic enzymes (zymogens) that once present in the small bowel, become activated and perform their major digestive functions by breaking down proteins, fat.

 Pancreatic juice, composed of the secretions of both ductal and acinar cells, is made up of the following digestive enzymes:

Trypsinogen, which is an inactive(zymogenic) protease that, once activated in the duodenum, into trypsin, breaks down proteins at the basic amino acids.

Chymotrypsinogen, which is a inactive(zymogenic) protease that once activated by duodenal enterokinase, breaks down proteins at their aromatic amino acids.

Carboxypeptidase, which is a protease that takes off the terminal amino acid group from a protein

Several elastases that degrade the protein elastin and some other proteins.

Pancreatic lipase that degrades triglycerides into fatty acids and glycerol.

Cholesterol esterase 

Phospholipase 

Several nucleases that degrade nucleic acids, like DNAase and RNAase

Pancreatic amylase that, besides starch, and glycogen, degrades most other carbohydrates.

Congenital Anomalies of the pancreas

Agenesis

Very rarely, the pancreas may be totally absent, a condition usually (but not invariably) associated with additional severe malformations that are incompatible with life.

Pancreas divisum

 is the most common clinically significant congenital pancreatic anomaly, with an incidence of 3% to 10%. It occurs when the fetal duct systems of the pancreatic primordia fail to fuse. As a result, the main pancreatic duct (Wirsung) is very short and drains only a small portion of the head of the gland, while the bulk of the pancreas drains through the minor sphincter. The relative stenosis caused by the bulk of the pancreatic secretions passing through the minor sphincter predisposes such individuals to chronic pancreatitis.

Annular pancreas

is a relatively uncommon variant on pancreatic fusion; the outcome is a ring of pancreatic tissue that completely encircles the duodenum. It can present with signs and symptoms of duodenal obstruction such as gastric distention and vomiting.

Ectopic Pancreas

Aberrantly situated, or ectopic, pancreatic tissue occurs in about 2% of the population; favored sites are the stomach and duodenum, followed by the jejunum, Meckel diverticulum, and ileum. These embryologic rests are typically small (millimeters to centimeters in diameter) and are located in the submucosa; they are composed of normal pancreatic acini with occasional islets. Though usually incidental and asymptomatic, ectopic pancreas can cause pain from localized inflammation, or-rarely-can cause mucosal bleeding. Approximately 2% of islet cell tumors arise in ectopic pancreatic tissue.

Congenital cysts

probably result from anomalous ductal development. In polycystic disease, kidney, liver, and pancreas can all contain cysts. Pancreatic cysts range from microscopic to 5 cm in diameter. In general, unilocular cysts tend to be benign, while multilocular cysts are more often neoplastic and possibly malignant.

Pancreatitis:

 Pancreatitis is inflammation of the pancreas. Normally, digestive enzymes secreted by the pancreas do not become active until they reach the small intestine. But when the pancreas is inflamed, the enzymes inside it attack and damage the tissues that produce them. Pancreatitis can be acute or chronic. Either form is serious and can lead to complications. In severe cases, bleeding, infection, and permanent tissue damage may occur.

acute pancreatitis

Acute pancreatitis is inflammation of the pancreas that occurs suddenly and usually resolves in a few days with treatment. Acute pancreatitis can be a life-threatening illness with severe complications. The most common cause of acute pancreatitis is the presence of gallstones that cause inflammation in the pancreas as they pass through the common bile duct. Chronic, heavy alcohol use is also a common cause. Acute pancreatitis can occur within hours or as long as 2 days after consuming alcohol. Other causes of acute pancreatitis include abdominal trauma, medications, infections, tumors, and genetic abnormalities of the pancreas.

Symptoms

Acute pancreatitis usually begins with gradual or sudden pain in the upper abdomen that sometimes extends through the back. The pain may be mild at first and feel worse after eating. But the pain is often severe and may become constant and last for several days. A person with acute pancreatitis usually looks and feels very ill and needs immediate medical attention. Other symptoms may include

a swollen and tender abdomen

nausea and vomiting

fever

a rapid pulse

Severe acute pancreatitis may cause dehydration and low blood pressure. The heart, lungs, or kidneys can fail. If bleeding occurs in the pancreas, shock and even death may follow.

Diagnosis

While asking about a person’s medical history and conducting a thorough physical examination, the doctor will order a blood test to assist in the diagnosis. During acute pancreatitis, the blood contains at least three times the normal amount of amylase and lipase, digestive enzymes formed in the pancreas. Changes may also occur in other body chemicals such as glucose, calcium, magnesium, sodium, potassium, and bicarbonate. After the person’s condition improves, the levels usually return to normal.

Diagnosing acute pancreatitis is often difficult because of the deep location of the pancreas. The doctor will likely order one or more of the following tests:

Abdominal ultrasound. Sound waves are sent toward the pancreas through a handheld device that a technician glides over the abdomen.

Computerized tomography (CT) scan. The CT scan is a noninvasive x ray that produces three-dimensional pictures of parts of the body. The person lies on a table that slides into a donut-shaped machine. The test may show gallstones and the extent of damage to the pancreas.

Endoscopic ultrasound (EUS). After spraying a solution to numb the patient’s throat, the doctor inserts an endoscope ,a thin, flexible, lighted tube down the throat, through the stomach, and into the small intestine. The doctor turns on an ultrasound attachment to the scope that produces sound waves to create visual images of the pancreas and bile ducts.

Magnetic resonance Imaging(MRI): A noninvasive test that produces cross-section images of parts of the body. After being lightly sedated, the patient lies in a cylinder-like tube for the test. The technician injects dye into the patient’s veins that helps show the pancreas, gallbladder, and pancreatic and bile ducts.

Treatment

Treatment for acute pancreatitis requires a few days’ stay in the hospital for intravenous (IV) fluids, antibiotics, and medication to relieve pain. The person cannot eat or drink so the pancreas can rest. If vomiting occurs, a tube may be placed through the nose and into the stomach to remove fluid and air.

Unless complications arise, acute pancreatitis usually resolves in a few days. In severe cases, the person may require nasogastric feeding—a special liquid given in a long, thin tube inserted through the nose and throat and into the stomach—for several weeks while the pancreas heals.

Before leaving the hospital, the person will be advised not to smoke, drink alcoholic beverages, or eat fatty meals. In some cases, the cause of the pancreatitis is clear, but in others, more tests are needed after the person is discharged and the pancreas is healed.

Therapeutic Endoscopic Retrograde Cholangiopancreatography (ERCP) for Acute and Chronic Pancreatitis

ERCP is a specialized technique used to view the pancreas, gallbladder, and bile ducts and treat complications of acute and chronic pancreatitis—gallstones, narrowing or blockage of the pancreatic duct or bile ducts, leaks in the bile ducts, and pseudocysts (accumulations of fluid and tissue debris).

Soon after a person is admitted to the hospital with suspected narrowing of the pancreatic duct or bile ducts, a physician with specialized training performs ERCP.

After lightly sedating the patient and giving medication to numb the throat, the doctor inserts an endoscope with a camera through the mouth, throat, and stomach into the small intestine. The endoscope is connected to a computer and screen. The doctor guides the endoscope and injects a special dye into the pancreatic or bile ducts that helps the pancreas, gallbladder, and bile ducts appear on the screen while x rays are taken.

People who undergo therapeutic ERCP are at slight risk for complications, including severe pancreatitis, infection, bowel perforation, or bleeding. Complications of ERCP are more common in people with acute or recurrent pancreatitis. A patient who experiences fever, trouble swallowing, or increased throat, chest, or abdominal pain after the procedure should notify a doctor immediately.

Complications

Gallstones that cause acute pancreatitis require surgical removal of the stones and the gallbladder. If the pancreatitis is mild, gallbladder removal( cholecystectomy)may proceed while the person is in the hospital. If the pancreatitis is severe, gallstones may be removed using therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Cholecystectomy is delayed for a month or more to allow for full recovery. If an infection develops, ERCP or surgery may be needed to drain the infected area( abscess). Exploratory surgery may also be necessary to find the source of any bleeding, to rule out conditions that resemble pancreatitis, or to remove severely damaged pancreatic tissue.

Pseudocysts that may develop in the pancreas can be drained using ERCP or EUS. If pseudocysts are left untreated, enzymes and toxins can enter the bloodstream and affect the heart, lungs, kidneys, or other organs.

Acute pancreatitis sometimes causes kidney failure. People with kidney failure need blood-cleansing treatments called dialysis or a kidney transplant.

In rare cases, acute pancreatitis can cause breathing problems. Hypoxia, a condition that occurs when body cells and tissues do not get enough oxygen, can develop. Doctors treat hypoxia by giving oxygen to the patient. Some people still experience lung failure and require a respirator for a while to help them breathe

chronic pancreatitis

Chronic pancreatitis is inflammation of the pancreas that does not heal or improve(it gets worse over time and leads to permanent damage). Chronic pancreatitis, like acute pancreatitis, occurs when digestive enzymes attack the pancreas and nearby tissues, causing episodes of pain. Chronic pancreatitis often develops in people who are between the ages of 30 and 40.

The most common cause of chronic pancreatitis is many years of heavy alcohol use. The chronic form of pancreatitis can be triggered by one acute attack that damages the pancreatic duct. The damaged duct causes the pancreas to become inflamed. Scar tissue develops and the pancreas is slowly destroyed.

Other causes of chronic pancreatitis are

hereditary disorders of the pancreas

cystic fibrosis(the most common inherited disorder leading to chronic pancreatitis)

hypercalcemia

hyperlipidemia or hypertriglyceridemia

some medicines

certain autoimmune conditions

unknown causes

Hereditary pancreatitis can present in a person younger than age 30, but it might not be diagnosed for several years. Episodes of abdominal pain and diarrhea lasting several days come and go over time and can progress to chronic pancreatitis. A diagnosis of hereditary pancreatitis is likely if the person has two or more family members with pancreatitis in more than one generation.

Symptoms

Most people with chronic pancreatitis experience upper abdominal pain, although some people have no pain at all. The pain may spread to the back, feel worse when eating or drinking, and become constant and disabling. In some cases, abdominal pain goes away as the condition worsens, most likely because the pancreas is no longer making digestive enzymes. Other symptoms include:

nausea

vomiting

weight loss

diarrhea

oily stools

People with chronic pancreatitis often lose weight, even when their appetite and eating habits are normal. The weight loss occurs because the body does not secrete enough pancreatic enzymes to digest food, so nutrients are not absorbed normally. Poor digestion leads to malnutrition due to excretion of fat in the stool.

Diagnosis

Chronic pancreatitis is often confused with acute pancreatitis because the symptoms are similar. As with acute pancreatitis, the doctor will conduct a thorough medical history and physical examination. Blood tests may help the doctor know if the pancreas is still making enough digestive enzymes, but sometimes these enzymes appear normal even though the person has chronic pancreatitis.

In more advanced stages of pancreatitis, when malabsorption and diabetes can occur, the doctor may order blood, urine, and stool tests to help diagnose chronic pancreatitis and monitor its progression.

After ordering x rays of the abdomen, the doctor will conduct one or more of the tests used to diagnose acute pancreatitis abdominal ultrasound, CT scan, EUS, and MRI.

Treatment

Treatment for chronic pancreatitis may require hospitalization for pain management, IV hydration, and nutritional support. Nasogastric feedings may be necessary for several weeks if the person continues to lose weight.

When a normal diet is resumed, the doctor may prescribe synthetic pancreatic enzymes if the pancreas does not secrete enough of its own. The enzymes should be taken with every meal to help the person digest food and regain some weight. The next step is to plan a nutritious diet that is low in fat and includes small, frequent meals. A dietitian can assist in developing a meal plan. Drinking plenty of fluids is also important.

People with chronic pancreatitis are strongly advised not to smoke or consume alcoholic, even if the pancreatitis is mild or in the early stages.

Complications

People with chronic pancreatitis who continue to consume large amounts of alcohol may develop sudden bouts of severe abdominal pain.

As with acute pancreatitis, ERCP is used to identify and treat complications associated with chronic pancreatitis such as gallstones, pseudocysts, and narrowing or obstruction of the ducts. Chronic pancreatitis also can lead to calcification of the pancreas, which means the pancreatic tissue hardens from deposits of insoluble calcium salts. Surgery may be necessary to remove part of the pancreas.

In cases involving persistent pain, surgery or other procedures are sometimes recommended to block the nerves in the abdominal area that cause pain.

When pancreatic tissue is destroyed in chronic pancreatitis and the insulin-producing cells of the pancreas, called beta cells, have been damaged, diabetes may develop. People with a family history of diabetes are more likely to develop the disease. If diabetes occurs, insulin or other medicines are needed to keep blood glucose at normal levels. A health care provider works with the patient to develop a regimen of medication, diet, and frequent blood glucose monitoring.

Injuries of pancreas:

 Injury to the pancreas, because of its retroperitoneal location, is a rare occurrence, most commonly seen with penetrating injuries (gun shot or stab wounds). Blunt trauma to the pancreas accounts for only 25% of the cases. Pancreatic injuries are associated with high morbidity and mortality due to accompanying vascular and duodenal injuries. Pancreatic injuries are not always easy to diagnose resulting in life threatening complications. Physical examination as well as serum amylase is not diagnostic following blunt trauma. Computed tomography (CT) scan can delineate the injury or transaction of the pancreas. Endoscopic retrograde pancreaticography (ERCP) is the main diagnostic modality for evaluation of the main pancreatic duct. Unrecognized ductal injury leads to pancreatic pseudocyst, fistula, abscess, and other complications. Management depends upon the severity of the pancreatic injury as well as associated injuries. Damage control surgery in hemodynamic unstable patients reduces morbidity and mortality.

Presentation

The type of injury (blunt or penetrating) and information about the injuring agent (eg, knife) help focus the clinician on the possibility of pancreatic injury.

During the physical examination, seat belt marks, flank ecchymoses, or penetrating injuries should alert the physician to the potential for pancreatic injury. Pancreatic injury can be frighteningly symptom free early in the post injury time frame and even silent in many cases. Rarely, a contained fracture of the spleen with retroperitoneal hematoma or leak manifests as dull epigastric pain or back pain, but the more common scenario is for patients to exhibit severe peritoneal irritation and a positive abdominal examination finding, usually caused by injury to other organs. Symptoms of injury to other structures commonly mask or supersede that of pancreatic injury, both early and late in the hospital course. Therefore, a high degree of clinical awareness is necessary to ensure that pancreatic injuries are not overlooked or missed, either early in the course of trauma or later in the ICU when the patient is not clinically improving as expected.

IndicationsCT scan findings of pancreatic trauma are generally categorized as direct signs (eg, pancreatic laceration) that tend to be specific but lack sensitivity and indirect signs (eg, peripancreatic fluid) that tend to be sensitive but lack specificity.[2]

Laboratory Studies

Blood work is unreliable when used to help diagnose blunt or penetrating trauma to the pancreas. Amylase and lipase levels may be within reference ranges, even in the presence of ductal disruption and pancreatic transection. Normal blood work findings do not guarantee or exclude pancreatic injury. Elevation in amylase levels is suggestive of pancreatic injury or inflammation but is not diagnostic. Elevated amylase levels in trauma may be from salivary glands, small bowel injury, ovarian injury, or a host of other sources. In some studies, amylase elevation was not observed until 3-4 hours after injury and, in some cases, not at all. Lipase levels are no more specific for pancreatic injury. This method has been used more frequently in children, but recent reports suggest that it may not be as cost-effective for screening pediatric pancreatic injuries as once thought.

Amylase detected in diagnostic peritoneal lavage (DPL) fluid is much more sensitive and specific for pancreatic injury than blood or serum amylase determinations. However, this study is not a standard or routine test in most institutions and may take significantly longer than anticipated to perform and to receive results unless previous arrangements or protocols are in effect with the diagnostic laboratory.

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Imaging Studies

Plain films of the abdomen may show pancreatic calcification from previous episodes of pancreatitis but are rarely of any benefit in detecting blunt trauma. These films can be valuable in detecting penetrating trauma by visualizing and localizing foreign bodies such as bullet fragments and projectile-induced bony injury. Frequently, these films can be obtained simultaneously with the bony pelvis films advocated by advanced trauma life support (ATLS) protocols in trauma victims by use of a larger x-ray plate and widening of the field of x-ray exposure.

Kidney, ureter, bladder (KUB) film or upright abdominal films rarely provide useful information and only serve to delay the implementation of further care or diagnostic measures.

While not specifically useful in the detection of pancreatic trauma, the upright chest film may show free air under the diaphragm, which is suggestive of an associated gastric, duodenal, or small bowel injury and is frequently associated with pancreatic injury.

CT scan

In a patient who is hemodynamically stable, a CT scan provides the safest and most comprehensive means of diagnosis of pancreatic injury. Laparotomy has a higher sensitivity but is not a reasonable screening test for all suspected cases of pancreatic injury.

A CT scan of the abdomen provides the simplest and least invasive diagnostic modality currently available to aid in the detection of a stable blunt pancreatic injury. However, this study is only rarely useful in acute penetrating injury.

A workup for patients who are stable and have knife wounds to the back or flank may include a CT scan, but a patient who is unstable must never be placed in the CT scanner, whether the injury is blunt or penetrating trauma.

CT scan is contraindicated in patients who are hemodynamically unstable or who have a penetrating trauma in which the decision for operative intervention has been made.

A CT scan of the pancreas is also useful in the follow-up care of patients with a pancreatic injury and trauma. Traumatic pancreatic cysts, pseudocysts, delayed ductal injury, pancreatic transection, pancreatitis, abscess, pancreatic necrosis, and splenic artery aneurysms may be noted after surgery or after the patient is released from the hospital.

Magnetic resonance imaging (MRI) is being used more frequently in assess injury to the ductal components but has not been prospectively compared to CT or other modalities.

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Other Tests

Intraoperative cholangiograms and pancreatic ductograms, especially with reflux into the pancreatic ducts (eg, Wirsung, Santorini), frequently provide information regarding the status of the injured pancreas when direct visualization is not helpful. Some authors recommend that these studies be performed during operative exploration, noting that they may help decrease complications due to missed pancreatic ductal injuries.

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Diagnostic Procedures

In the patient who is unstable, operative exploration provides the optimal diagnostic tool for pancreatic injury. As in blunt trauma, endoscopic retrograde cholangiopancreatography (ERCP) or intraoperative dye studies may provide more information in a select patient population.

ERCP is increasingly being used to help diagnose, both immediately and in delayed fashion, the presence of pancreatic ductal injuries. Some authors suggest early ERCP (ie, within 6-12 h of injury) to minimize delayed complications. While extremely helpful, this procedure has potential complications that can limit its usefulness in patients with pancreatic trauma. For it to be of benefit, the endoscopist must be skilled and experienced in its use in the injured and potentially severely ill trauma patient. This is especially true when used in the operating room in a patient with an open abdomen who is at risk for hypothermia with exposed abdominal contents.

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Histologic Findings

Histologic examination of the resected pancreas documents the presence of hemorrhage and, frequently, of crush injuries to the tissue. Occasionally, this examination may reveal chronic preexisting pancreatic conditions such as pancreatitis, saponification, scarring, or tumors.

Pancreatic cancer (Causes)

While it can seldom be explained why one person gets pancreatic cancer and another doesn t, it is clear that the disease is not contagious. No one can "catch" cancer from another person.

Although scientists do not know exactly what causes cancer of the pancreas, they are learning that some things increase a person s chance of getting this disease. Smoking is a major risk factor. Research shows that cigarette smokers develop cancer of the pancreas two to three times more often than nonsmokers. Quitting smoking reduces the risk of pancreatic cancer, lung cancer, and a number of other diseases.

 symptoms and signs

Pancreatic cancer has been called a "silent" disease because early pancreatic cancer usually does not cause symptoms. If the tumor blocks the common bile duct and bile cannot pass into the digestive system, the skin and whites of the eyes may become yellow, and the urine may become darker. This condition is called jaundice.

As the cancer grows and spreads, pain often develops in the upper abdomen and sometimes spreads to the back. The pain may become worse after the person eats or lies down. Cancer of the pancreas can also cause nausea, loss of appetite, weight loss, and weakness.

A rare type of pancreatic cancer, called islet cell cancer, begins in the cells of the pancreas that produce insulin and other hormones. Islet cells are also called the islets of Langerhans. Islet cell cancer can cause the pancreas to produce too much insulin or hormones. When this happens, the patient may feel weak or dizzy and may have chills, muscle spasms, or diarrhea.

These symptoms may be caused by cancer or by other, less serious problems. If an individual is experiencing symptoms, a doctor should be consulted.

Treatment

Treatment for pancreatic cancer depends on a number of factors. Among these are the type, size, and extent of the tumor as well as the patient s age and general health. A treatment plan is tailored to fit each patient s needs.

Cancer of the pancreas is curable only when it is found in its earliest stages, before it has spread. Otherwise, it is very difficult to cure. However, it can be treated, symptoms can be relieved, and the quality of the patient s life can be improved.

Pancreatic cancer is treated with surgery, radiation therapy, or chemotherapy. Researchers are also studying biological therapy to see whether it can be helpful in treating this disease. Surgery may be done to remove all or part of the pancreas. Sometimes it is also necessary to remove a portion of the stomach, the duodenum, and other nearby tissues. This operation is called a Whipple procedure. In cases where the cancer in the pancreas cannot be removed, the surgeon may be able to create a bypass around the common bile duct or the duodenum if either is blocked.

Radiation therapy uses high-powered rays to damage cancer cells and stop them from growing. Radiation is usually given 5 days a week for 5 to 6 weeks. This schedule helps to protect normal tissue by spreading out the total dose of radiation. The patient doesn t need to stay in the hospital for radiation therapy.

Radiation is also being studied as a way to kill cancer cells that remain in the area after surgery. In addition, radiation therapy can help relieve pain or digestive problems when the common bile duct or duodenum is blocked.

Chemotherapy uses drugs to kill cancer cells. The doctor may use just one drug or a combination. Chemotherapy may be given by mouth or by injection into a muscle or vein. The drugs enter the bloodstream and travel through the body. Chemotherapy is usually given in cycles; a treatment period followed by a recovery period, then another treatment period, and so on.