• review the exocrine and endocrine secretions of the pancreas;
• outline the diagnostic tests for pancreatitis;
• describe the control of pancreatic secretion;
• explain the effects of acute and chronic pancreatitis.
Jude is a 22-year-old woman who was taken to hospital one morning complaining of knife-like, severe upper-abdominal pain, nausea, vomiting and fever. She stated that she had been feeling quite well until this morning, when her symptoms came on suddenly. On questioning, the patient admitted that she routinely consumed very large amounts of alcohol and that she had drunk rather more than usual during the preceding two weeks as she was ‘celebrating’. In addition, she also revealed that her boyfriend had recently been admitted to hospital suffering from hepatitis.
What is likely to be the initial diagnosis of Tude’s symptoms and why?
Because of her symptoms and the illness suffered by Jude’s boyfriend, a tentative diagnosis of infectious hepatitis is initially made.
On further testing, a specimen of urine showed a normal colour and the patient did not appear to be jaundiced. In addition, a CT (computerized tomography) scan showed that her liver and bile duct were normal, and she had no history of stomach (peptic) ulcers.
Are the results in Part 2 consistent with the initial diagnosis? Give reasons for your answer.
No. Jude showed no signs of jaundice, such as a yellow tinge to the skin. In addition, her scans, which could have indicated a problem with her liver or gall stones, revealed a normal liver and bile duct.
What signs could indicate that Tude was jaundiced and why is the colour of her urine significant?
Signs of jaundice: jaundice gives a yellowish colour to the skin and mucous membranes, usually easiest to see in the cornea. The yellow colour is due to the presence of breakdown products of haemoglobin such as bilirubin in tissues, which the liver usually removes from the blood. Jaundice is indicative of liver disease, obstruction of the bile ducts or haemolytic disease. Bilirubin stains not only the tissues but also all body fluids, including plasma and urine, and the patient’s urine can become really dark.
On admission to the ward Jude had blood samples taken for biochemical tests. Her serum amylase activity was markedly increased and after a day her lipase was also significantly raised. The pattern of change in Jude’s enzymes was as follows: amylase rose quite quickly over the 3-12 hours after onset of symptoms and fell back to the normal value in three to four days; this rise was sharp and prominent. The increase in lipase was slower and more prolonged, lasting about seven days. Jude was given pain relief, and an intravenous catheter was inserted for a glucose and saline drip, with orders that she be given nothing by mouth.
With appropriate pain control, Jude soon felt better and her recovery was complete.
What is the ultimate diagnosis of Jude’s symptoms?
The revised diagnosis is pancreatitis as the patient did not appear to be jaundiced and a specimen of urine showed a normal colour. Her pain and other symptoms are consistent with pancreatic inflammation.
Why do you think there was an instruction to give Jude nothing by mouth? And why was a mixture of glucose and saline given intravenously?
Nothing is given by mouth, to minimize stimulation of the pancreas. Secretion of fluid and enzymes from the pancreas is stimulated by the presence of chyme in the small intestine. Fluids given by mouth will enter the duodenum and stimulate pancreatic secretion; this must be reduced to a minimum in order to reduce further irritation of the inflamed pancreas and to ‘rest’ the tissue. The fluids which will be needed to replace water lost through vomiting are therefore given by the intravenous route. In some patients gastric fluids secreted by the chief and parietal cells of the gastric mucosa are aspirated from the stomach, to ensure nothing passes into the duodenum. Glucose and saline are administered intravenously to maintain blood glucose in the normal range, to ensure that the patient is adequately hydrated and has a urine output.
What is the function of amylase in the human gut and which other gut structures produce an amylase?
Alpha-amylase (a-amylase) is concerned with the digestion of starch to disaccharides and other products in the gut. The salivary glands also produce a-amylase, the parotid glands producing the greatest amount.
List the digestive enzymes (at least five) which are produced by the pancreas.
Pancreatic exocrine tissue produces amylase, lipase and a range of serine proteases, enzymes such as trypsin (which is also elevated in pancreatitis), chy-motrypsin and elastase, also nucleases, carboxypeptidase and aminopeptidase.
In pancreatitis the pancreas is damaged by some of these enzymes. Why is the normal pancreas not affected by the enzymes it produces?
The normal pancreas is not damaged by the enzymes it produces because they are produced and stored in an inactive form, for example trypsinogen and chymotrypsinogen.
When trypsinogen enters the small intestine, it is converted to trypsin by enterokinase. The trypsin produced then converts chymotrypsinogen and other proteolytic enzymes to their active form.
Outline the actions of amylase on the gut contents, naming the products of digestion.
Actions of a-amylase on gut content: a-amylase hydrolyses the 1,4-a-glyco-sidic bonds of glucose polymers in starches. The products are the disaccharide maltose and oligosaccharides. Digestion to monosaccharides is completed when the chyme contacts the intestinal mucosa, as maltase is present in the brush border of these cells. Maltase converts maltose to glucose. A large amount of starch is consumed in the average diet, so amylase is an important digestive enzyme.
The low concentration of amylase normally found in the blood has been produced in small amounts by many tissues, but the greatest amounts are produced by the pancreas and the parotid salivary gland.
What factors normally control pancreatic enzyme secretion?
Normally, pancreatic secretion is stimulated by eating. The factors involved are both nervous and hormonal. Pancreatic secretion is increased by vagal (parasympathetic) stimulation and inhibited by sympathetic stimulation. Cholecystokinin (CCK), released from the wall of the duodenum, stimulates pancreatic juice, which is rich in enzymes. Secretin (the first hormone to be discovered, by Bayliss and Starling), which is also produced in the duodenum, stimulates a pancreatic fluid with a high bicarbonate content.
Comment on the tests which aid diagnosis in suspected pancreatitis.
The most useful tests in suspected pancreatitis are biochemical: the tests involve measurements of the concentration of amylase and lipase in blood. Increased blood levels of a-amylase can be found in a number of other conditions, for example disease of the ovaries, but elevated amylase is most often seen in acute and chronic pancreatitis. During acute attacks, the blood can contain three to five times more amylase and lipase than normal and the pattern of change is characteristic.
The pancreas has both endocrine and exocrine cells. What is the difference between endocrine and exocrine secretions?
Endocrine secretions are hormones, substances made in a location from which they are carried in blood to their site of action elsewhere. Exocrine secretions are produced and secreted into another organ or onto the body surface, usually via ducts which carry them to their site of action.
Which hormones are produced by the pancreas?
The pancreas produces hormones in areas of endocrine tissue: the islets of Langerhans. The major hormones are insulin, from the beta-cells (/J-cells), and glucagon, from alpha-cells (a-cells). Delta cells produce somatostatin.
Comment on the relationship between the development of pancreatitis and alcohol consumption.
Excessive alcohol consumption damages the pancreas. Patients usually develop pancreatitis after many years of excessive alcohol consumption, but occasionally it can occur after only one year of heavy drinking. There is no safe level of alcohol intake, below which no damage to the pancreas can occur: even moderate or social drinkers are at risk. Some people have more than one attack of pancreatitis and recover well from each, but in a few individuals acute pancreatitis can be severe, and a life-threatening illness develops.
Why do you think a high amylase and lipase concentration was found in Jude’s blood?
Reasons for observing high concentrations of amylase and lipase in the blood: consumption of large amounts of alcohol appears to cause inflammation of and damage to the pancreatic exocrine cells. Some researchers think that pancreatic cells may become sensitized to alcohol and be further affected even if only very small amounts of alcohol are taken. Following secretory cell damage, the enzymes leak out into surrounding areas, irritating the secretory cells, causing further enzyme release, then oedema, haemorrhage and cell death. Trypsin and chymotrypsin appear to initiate the process and in turn activate other pro-enzymes, which damage tissues further. The large quantity of released enzymes passes into tissue fluids and into the plasma, causing the blood concentration of amylase to rise rapidly following pancreatic damage. This pattern, of rapid rise in amylase and the slower, more sustained rise in lipase, is characteristic of pancreatitis and is a simple test which aids differential diagnosis of the condition.
Explain why chronic pancreatitis leads to malnutrition and weight loss.
In pancreatitis the cells which produce enzymes are damaged and the quantity of enzymes entering the duodenum is reduced. At some point there will be an inadequate amount of enzyme to deal with carbohydrate and, particularly, with lipids in the diet. A considerable portion of the daily calorie intake will not be digested or absorbed, and fat-soluble vitamin absorption will be compromised. Patients will suffer from malabsorption, particularly of fats. In a normal individual <7% of dietary fat passes through the gut undigested. Patients with pancreatic insufficiency may excrete >20% of their dietary fat unchanged, a condition known as steatorrhoea. Faeces which contain large quantities of undigested fat float in water and also smell very unpleasant. When high alcohol consumption continues year on year, a chronic pancreatitis may develop causing increasing and irreversible loss of pancreatic tissue. The secretion of enzymes into the duodenum is then permanently reduced to a very low level. Since these patients often replace meals with alcohol, their food intake is unlikely to be well balanced. The combination of inadequate digestion and absorption of nutrients with an inadequate dietary intake leads to deficiency of both specific nutrients and total calories, resulting in malnutrition and weight loss.
Patients maybe prescribed an enzyme supplement, which is added to food to allow digestion of dietary fat. This both reduces the steatorrhoea and helps the patient to regain lost weight.
• The pancreas secretes a variety of enzymes into the gut. These include: proteolytic enzymes, such as trypsin and chymotrypsin, lipase and amylase. The salivary glands also produce an amylase. The major hormones produced by the pancreas are insulin, glucagon and somatostatin.
• Inflammation of the pancreas, pancreatitis, can be a consequence of excessive alcohol intake and causes severe pain. In chronic pancreatitis the exocrine cells which produce enzymes are damaged and smaller quantities of enzyme are released into the gut so that a major portion of the diet remains undigested and is not absorbed. Patients suffer malnutrition and weight loss.
• Pancreatic secretion is controlled by nervous and hormonal factors. Both vagal stimulation and the hormones secretin and CCK, released from the duodenum, stimulate secretion. In acute pancreatitis nothing is given by mouth, in order to minimize pancreatic stimulation and to rest the pancreas. Fluid and glucose are given intravenously to maintain hydration.
• Certain biochemical changes are useful in diagnosing pancreatitis: pancreatic damage results in amylase and lipase being released into the blood. Amylase concentration rises over 3-12 hours and returns to normal in three to four days. The rise in lipase is slower and restoration of normal blood levels takes longer.
• Hepatitis could result in symptoms similar to those experienced in this case study, but would be likely to cause jaundice, a yellow skin colouration which is due to the presence of haemoglobin breakdown products in the tissues.