1. Pancreatic Function Tests
Physiology of pancreas.
Diseases of the pancreas.
Cystic fibrosis.
Pancreatic carcinoma.
Pancreatitis.
Tests of pancreatic function.
Secretin/CCK.
Fecal fat analysis.
Sweat electrolyte determinations.
Serum enzymes: amylase and lipase.
Other tests of pancreatic function.

2. Case 1
A 53-year old man, who admitted to a heavy alcohol intake for many years, developed severe abdominal pain which radiated through to the back. He had no previous history of GIT disease. On examination, the patient was mildly shocked and his abdomen was tender in the epigastric area. There was no evidence of either intestinal obstruction or perforation. Blood was taken for urgent biochemical examinations.

3. Case 1
Urea 10mmol/L Creatinine 90µmol/L Calcium 2.10 mmol/L Albumin 30 g/L Glucose 12 mmol/L Amylase 5000 IU/L ˂ 300

4. Case 1 What is the likely diagnosis of this patient?
Can we use the elevated amylase level alone for the diagnosis?
Why is the urea raised without the increase in creatinine?
Why is the protein low?
Comment on the hypocalcemia.
The amylase alone cannot be used for the diagnosis.
Pancreatitis.
In this case the history is very suggestive of pancreatitis.
The slightly raised urea, can be explained by renal hypoperfusion due to shock.
Loss of protein rich exudates into the peritoneal cavity causes a fall in plasma proteins.
Low albumin might contribute to hypocalcemia, the formation of insoluble calcium salts of fatty acids, released within and around the inflamed pancreas.
Hyperglycemia may occur, but usually transient.

5. Physiology of pancreas
Digestive gland.
Endocrine and exocrine tissues.
Endocrine: hormone-releasing.
Islets of Langerhans
Four different cell types
Four different hormones: insulin, glucagon, gastrin and somatostatin
Exocrine: enzyme releasing
1.5-2 L/day of fluid
Rich in digestive enzymes
Empty into the duodenum

8. The pancreas is a large gland that is involved in the digestive process and located outside of the gastrointestinal.
It is composed of both endocrine and exocrine tissue.
The endocrine functions of the pancreas include production of insulin and glucagon which are involved in carbohydrate metabolism.
Exocrine function involves the production of many enzymes used in the digestive process.

9. The pancreas is composed of two morphologically and functionally different tissues: endocrine tissue and exocrine tissue

10. Endocrine function
The endocrine (hormone-releasing) component is by far the smaller of the two and consists of the islets of Langerhans, which are spherical or ovoid clusters composed of at least four different cell types.
The islet cells secrete:
Insulin
Glucagon
Gastrin
Somatostatin
Gastrin
Gastrin is a major physiological regulator of gastric acid secretion
It also has an important trophic or growth-promoting influence on the gastric mucosa.
Somatostatin
A hormone widely distributed throughout the body, especially in the hypothalamus and pancreas.
It acts as an important regulator of endocrine and nervous system function by inhibiting the secretion of several other hormones such as growth hormone, insulin and gastrin.

11. Exocrine function
The larger, exocrine pancreatic component (enzyme-secreting) secretes about L/day of fluid, which is rich in digestive enzymes, into ducts that ultimately empty into the duodenum.
This digestive fluid is produced by pancreatic acinar cells.
Protein rich, pancreatic fluid is clear, colorless and watery, with alkaline pH; pH can reach up to 8.3 which is used eventually to neutralize the hydrochloric acid.
Bicarbonate and chloride vary reciprocally  150 mmol/L.
Digestive enzymes secreted by the pancreas.
Proteolytic enzymes: trypsin, chymotrypsin, elastase, collagenase, leucine aminopeptidase, carboxypeptidases.
Lipid-digesting enzymes: lipase and lecithinase.
Carbohydrate-splitting: amylase.
Ribonucleases.

12. This digestive fluid is produced by pancreatic acinar cells (grape-like clusters), which line the pancreas and are connected by small ducts.
These small ducts empty into progressively larger ducts, eventually forming one major pancreatic duct and a smaller accessory duct.
The major pancreatic duct and the common bile duct open into the duodenum

14. Control of pancreatic activity
Pancreatic activity is under both nervous and endocrine control.
Nervous control:
Vagus nerve can cause small amount of pancreatic fluid secretion when food is smelled or seen, and these secretions may increase as the bolus of food reaches the stomach.
Endocrine control: Most of the pancreatic action, however, is under the hormonal control.
Secretin: is mainly produced in mucosa of duodenum:
Secretin stimulates the release of bicarbonate-rich fluid which protects the lining of the intestine from damage.
It inhibits gastrin activity in stomach.
The pancreatic fluid contains few digestive enzymes.

15. Control of pancreatic activity
2. Cholecystokinin (CCK):
Is secreted from mucosal epithelial cells in the first segment of the small intestine (duodenum).
Stimulates delivery of digestive enzymes from the pancreas and bile from the gallbladder into the small intestine.
Is stimulated by the presence of fats or amino acids in the duodenum.
Releases enzymes into the pancreatic fluid.

16. Diseases of the pancreas
Cystic fibrosis
Pancreatic carcinoma
Pancreatitis

17. Cystic fibrosis Inherited autosomal recessive disorder.
The disease is relatively common and occurs in about 1 of 1600.
Cystic fibrosis affects multiple parts of the body, it is characterized by dysfunction of mucous and exocrine glands throughout the body.
It can be presented as: intestinal obstruction of the newborn, excessive pulmonary infections in children, pancreatogenous malabsorption in adults.
The small and large ducts and the acni dilate and convert into small cysts filled with mucus.
Fibrous scaring with corresponding decrease in function leading prevention of pancreatic secretions reaching the duodenum.
As the disease progresses, there is increased destruction and fibrous scarring of the pancreas.

18. Cystic fibrosis is transmitted as an autosomal recessive disorder.

19. The cystic fibrosis gene known as CFTR (cystic fibrosis transmembrane conductor regulator) occurs on chromosome 7, and more than 900 mutations causing this disorder have been identified; however, some occur more commonly than others.

20. Cystic fibrosis
Cystic fibrosis affects multiple parts of the body including the pancreas, the sweat glands, and the lungs. 

21. Cystic fibrosis
Normal People have a small layer of salt water in the large airways of their lungs. 
This layer of salt water is under the mucus layer which lines the airways. 
The mucus layer in the airways helps to clear dust and other inhaled particles from the lungs
In people without cystic fibrosis, working cystic fibrosis proteins allow salt (chloride) to enter the air space and water follows by osmosis.  The mucus layer is dilute and not very sticky.

22. In people with cystic fibrosis, non-working cystic fibrosis proteins mean no salt (chloride) enters the air space and water doesn't either.  The mucus layer is concentrated and very sticky.

23. Cystic fibrosis

24. Pancreatic Carcinoma
Pancreatic carcinoma is the fifth most frequent form of fatal cancer.
More than 90% of patients die within 1 year of diagnosis.
Most pancreatic tumors arise as adenocarcinomas of the ductal epithelium. Because the pancreas has a rich supply of nerves, pain is a prominent feature of the disease.
If the tumor arises in the tail of the pancreas, detection does not often occur until an advanced stage of the disease because of its central location and the associated vague symptoms.
Cancer of the head of the pancreas is usually detected earlier because of its proximity to the common bile duct.
Signs of these tumors are jaundice, weight loss, anorexia, and nausea.
Jaundice is associated with signs of posthepatic hyperbilirubinemia (intrahepatic cholestasis) and low levels of fecal bilirubin, resulting in clay colored stools.
Adenocarcinomas (Cancer that begins in cells that line the inside of organs, these organs make substances like hormones or milk).

25. Pancreatic Carcinoma
Islet cell tumors of the pancreas affect the endocrine capability of the pancreas.
If the tumor occurs in beta cells, hyperinsulinism is often seen, resulting in low blood glucose levels, sometimes followed by hypoglycemic shock.
Pancreatic α-cell tumors, which overproduce gastrin, are called gastrinomas; they cause Zollinger-Ellison syndrome.
These tumors are associated with watery diarrhea, recurring peptic ulcer, and significant gastric hypersecretion and hyperacidity.
Pancreatic α -cell glucagon-secreting tumors are rare; the hypersecretion of glucagon is associated with diabetes mellitus.

26. Zollinger-Ellison syndrome (ZES)
Is a rare disorder that causes tumors in the pancreas and duodenum and ulcers in the stomach and duodenum.
The tumors secrete the gastrin hormone that causes the stomach to produce too much acid, which in turn causes stomach and duodenal ulcers (peptic ulcers) and tumors.
The ulcers caused by ZES are less responsive to treatment than ordinary peptic ulcers.
Physicians diagnose ZES through blood tests to measure levels of gastrin and gastric acid secretion and the presence of ulcers by endoscopy.
The primary treatment for ZES is by proton pump inhibitors that suppress acid production and promote healing are the first line of treatment lansoprazole.
Surgery to treat peptic ulcers or to remove tumors in the pancreas or duodenum are other treatment options.
The primary treatment for ZES is medication to reduce the production of stomach acid.

27. Pancreatitis Pancreatitis is inflammation of the pancreas.
Autodigestion of the pancreas as a result of reflux of bile or duodenal contents into the pancreatic duct.
Pathologic changes: acute edema with large amounts of fluid accumulating, cellular infiltration, necrosis of the acinar cells, with hemorrhage, intrahepatic and extrahepatic pancreatic fat necrosis.
Pancreatitis is generally classified as:
Acute (no permanent damage to the pancreas).
Chronic (irreversible injury).
Relapsing/recurrent, which can also be acute or chronic.
It commonly occurs in midlife.
Painful episodes can occur intermittently and frequently accompanied by nausea and vomiting.

28. Pancreatitis
Pancreatitis is often associated with alcohol abuse or biliary tract disease or rarely hypercalcemia, which is often associated with hyperparathyroidism.
Patients with hyperlipoproteinemia and those with hyperparathyroidism are also at a significantly increased risk for this disease.
Other etiologic factors associated with acute pancreatitis include mumps, obstruction caused by biliary tract disease, gallstones, pancreatic tumors, tissue injury, atherosclerotic disease, shock, pregnancy, hypercalcemia, hereditary pancreatitis, immunologic factors associated with postrenal transplantation, and hypersensitivity.
Symptoms of acute pancreatitis include severe abdominal pain.
The etiology of chronic pancreatitis is similar to that of acute pancreatitis, but chronic excessive alcohol consumption appears to be the most common predisposing factor.

29. Pancreatitis
Laboratory findings include increased amylase, lipase and triglycerides.
Hypocalcemia may be found because of sudden removal of large amounts of calcium from the extracellular fluid because of impaired mobilization or as a result of calcium fixation by fatty acids liberated by increased lipase action on triglycerides.
Hypoproteinemia is due mainly to the notable loss of plasma into the peritoneal space.
A shift of arterial blood flow from the inflamed pancreatic cells to less affected or normal cells causes oxygen deprivation and tissue hypoxia in the area of damage, including the surrounding organs and tissue.

30. Malabsorption syndrome
Is associated with all pancreatic diseases.
Diminished pancreatic exocrine function  compromise digestion and absorption of ingested nutrients  the general malabsorption syndrome.
Malabsorption is associated with abdominal bloating and discomfort; the frequent passage of bulky, malodorous feces and weight loss.
Failure to digest or absorb fats, known as steatorrhea renders a greasy appearance to feces.
The malabsorption syndrome typically involves abnormal digestion or absorption of proteins, polysaccharides, carbohydrates, and other complex molecules, as well as lipids.
Disturbances of electrolytes, water, vitamins (particularly fat soluble vitamins), and minerals.
In addition to pancreatic exocrine deficiency, the malabsorption syndrome can be caused by biliary obstruction, which deprives the small intestine of the emulsifying effect of bile, and various diseases of the small intestine, which inhibit absorption of digested products.

31. Tests of pancreatic function
Depending on etiology and clinical picture, pancreatic function may be suspect when there is increased amylase and lipase.
Tests that used for detection of malabsorption: examination of stool for excess fat, D-xylose test, and fecal fat analysis.
Tests measuring other exocrine function: secretin, CCK, fecal fat, trypsin, and chymotrypsin.
Tests assessing changes associated with extrahepatic obstruction: bilirubin.
Endocrine-related tests that reflect changes in the endocrine cells of the pancreas: gastrin, insulin, and glucose.

32. Tests of pancreatic function
Direct evaluation of pancreatic fluid may include:
Measurement of the total volume of pancreatic fluid.
The amount or concentration of bicarbonate and enzymes, which requires pancreatic stimulation.
Stimulation may be accomplished using a pre-described meal or administration of secretin, which allows for volume and bicarbonate evaluation.
Secretin stimulation followed by CCK stimulation adds enzymes to the pancreatic fluid evaluation. The advantage of these tests is that the chemical and cytologic examinations are performed on actual pancreatic secretions which can often establish the presence, or at least the suspicion, of malignant neoplasms.

33. Tests of pancreatic function
Because of advances in imaging techniques, these stimulation tests are used less often.
Most of the tests have found clinical utility in excluding the pancreas from diagnosis.
The sweat test, used for screening cystic fibrosis, when used along with the clinical picture at the time of testing, can provide important diagnostic information.

34. Secretin/CCK test
Direct determination of the exocrine secretary capacity.
Intubation of the patient and fasting for 6-hours.
Pancreatic secretion is stimulated by I.V. administration of secretin followed by CCK.
Pancreatic secretions are collected.
pH, secretary rate, enzyme activities (trypsin, amylase, or lipase) and amount of bicarbonate are determined.
Assessment of enzymes must be taken in view of total volume output.
Decreased pancreatic flow is associated with pancreatic obstruction and increase in enzyme concentrations.
Low concentrations of bicarbonate and enzymes is associated with cystic fibrosis, chronic pancreatitis, pancreatic cysts, calcification and edema of pancreas.

35. Tests of pancreatic function

36. Lundh test
This is a direct test of pancreatic function in which duodenal contents are collected for two hours following a meal containing carbohydrate, protein and fat.
Low enzymatic activity-amylase, trypsin or lipase- indicates pancreatic insufficiency.
It is less informative than the secretin / CCK test because it does not differentiate between a decreased pancreatic response due to a reduced ability to secrete, or a reduced ability to transfer the stimulus, neutrally or hormonally.

37. Fecal fat analysis
Fecal lipids: fecal lipids are derived from four sources:
Unabsorbed ingested lipids.
Lipids excreted into the intestine (pre­dominantly in the bile).
Cells shed into the intestine.
Metabolism of intestinal bacteria.
Patients with lipid-free diets still excrete 1-4 g of lipids/24 hours.
With lipid-rich diet  normally up to 7 g/24 hours.
Increased fecal fat can be caused by biliary obstruction or disease of the small intestine.
Severe steatorrhea is due to exocrine pancreatic insufficiency or disease of the small intestine.
Qualitative and quantitative fecal fat analysis.

38. Fecal fat analysis Qualitative screening test for fecal fat
Fat soluble stains: Sudan III, Sudan IV which dissolve in and color lipid droplets.
Sudan Staining for fecal fat:
Neutral fats (triglycerides) and many other lipids stain yellow-orange to red with Sudan III because the dye is much more soluble in lipid than in water or ethanol.
Free fatty acids do not stain appreciably unless the specimen is heated in the presence of the stain with 36% acetic acid.

40. Fecal fat analysis Quantitative fecal fat analysis
The definitive test for steatorrhea is the quantitative fecal fat determination.
Usually 72-hour stool collection, although collection period may be increased to up to 5 days.
Gravimetric or titrimetric assay of fatty acids.

41. Sweat electrolyte determinations
Sodium and chloride concentration in sweat.
Significantly elevated concentrations of both ions occur in more than 99% of cystic fibrosis patients.
2-5 fold increase of sweat sodium and chloride in children.
Acquiring sweat specimens: pilocarpine nitarte administration by iontophoresis, collecting the sweat on a cotton gauze and then analysis of sweat.
Pilocarpine administration by iontophoresis is an efficient method for sweat collection and stimulation.
Iontophoresis employs an electric current that causes pilocarpine to migrate into a limited skin area.

44. Serum enzymes Amylase Diagnosis of acute pancreatitis.
It increases within few hours, reaches a peak in about 24 hours, returns back to normal in 3-5 days because of renal clearance.
Urine amylase is more sensitive indicator of acute pancreatitis.
The increase in the concentration cannot be correlated to the severity of the disease.
Amylase is an enzyme that helps digest carbohydrates. It is made in the pancreas and the glands that make saliva. When the pancreas is diseased or inflamed, amylase releases into the blood.
A test can be done to measure the level of this enzyme in your blood.
Amylase may also be measured with an amylase urine test.
α-Amylase[edit]
Alpha-Amylase Human salivary amylase: By acting at random locations along the starch chain, α-amylase breaks down long-chain carbohydrates, ultimately yielding maltotriose and maltose from amylose, or maltose, glucose and "limit dextrin" from amylopectin. Because it can act anywhere on the substrate, α-amylase tends to be faster-acting than β-amylase. In animals, it is a major digestive enzyme, and its optimum pH is 6.7–7.0.
In human physiology, both the salivary and pancreatic amylases are α-amylases.
The α-amylases form is also found in plants, fungi (ascomycetes and basidiomycetes) and bacteria (Bacillus)
β-amylase is also synthesized by bacteria, fungi, and plants

45. Serum enzymes Lipase Lipase increases in serum in acute pancreatitis.
Both amylase and lipase may be significantly increased in serum in many other conditions (eg, opiate administration, pancreatic carcinoma, intestinal infarction, obstruction or perforation, and pancreatic trauma).
Measurements of lipase has been reported to be a more specific test for acute pancreatitis more than amylase.
A combination of both has been reported to have specificity and approximately 90%.

46. Other Tests of Pancreatic Function
Gastrointestinal function
D-Xylose absorption test: a pentose sugar that does not require pancreatic enzymes for absorption. In a patient with a suspected malabsorption syndrome, a normal D-xylose points toward pancreatic insufficiency.
Radiographic tests
X-ray, ultrasound,…

47. The End