Chapter 13 Disorders of the Pancreas The Nature of Disease: Pathophysiology for the Health Professions, 2nd ed. Thomas H. McConnell

NORMAL PANCREATIC PHYSIOLOGY The exocrine pancreas excretes digestive juice into the intestine. Protease secreted as inactive enzyme (zymogen) Lipase and amylase secreted as active enzyme The endocrine pancreas excretes hormones into blood. Alpha cells: glucagon. Functional opposite of insulin, stimulates liver glycogen >> glucose. Raises blood glucose Beta cells: insulin. Opens cell membrane to glucose. Lowers blood glucose Delta cells: somatostatin. Inhibits glycogen formation and insulin secretion. Raises blood glucose PP cells: pancreatic polypeptide, acts on stomach to stimulate juices and slow intestinal motility

Figure 13.1 The pancreas and its anatomic relationships Figure 13.1 The pancreas and its anatomic relationships. Cross-section of the upper abdomen. View from inferior to pancreas, looking superiorly

Figure 13.2 Anatomic detail of the pancreas

Figure 13.3 Glucose, glycogen, insulin, and glucagon metabolism Figure 13.3 Glucose, glycogen, insulin and glucagon metabolism. Insulin promotes lower blood glucose by increasing peripheral cell glucose uptake. Glucagon promotes higher blood glucose by stimulating glycogen breakdown into glucose and glucose synthesis from amino acids. (Adapted with permission from McConnell TH, Hull KL. Human Form Human Function: Essentials of Anatomy & Physiology. Baltimore (MD): Wolters Kluwer Health; 2011.)

PANCREATITIS Acute pancreatitis causes reversible injury. Chronic alcohol abuse causes 2/3 of cases. Half of patients have gallstones. Chronic pancreatitis is associated with irreversible pancreatic injury. Repeated bouts of acute pancreatitis 5% of patients with stones develop pancreatitis.

Figure 13.4 The pathogenesis of acute pancreatitis Acinar injury or duct obstruction releases enzymes into tissue, where the enzymes digest fat and blood vessels.

Figure 13.5 Acute pancreatitis Figure 13.5 Acute pancreatitis. Dissection of esophagus, stomach, duodenum, gallbladder, and pancreas. The gallbladder is full of gallstones, and the surface of the pancreas is covered with an acute inflammatory exudate. Gallstones are an important cause of pancreatitis.

Figure 13.6 Acute hemorrhagic pancreatitis Figure 13.6 Acute hemorrhagic pancreatitis. Multiple crosssections of the pancreas. Pancreatic injury or duct obstruction releases enzymes that digest fat and blood vessels, causing local hemorrhage.

Figure 13.7 The consequences of pancreatitis Figure 13.7 The consequences of pancreatitis. The consequences of acute and chronic pancreatitis are compared.

Figure 13.8 Gross anatomy of chronic pancreatitis Figure 13.8 Gross anatomy of chronic pancreatitis. The pancreas is abnormally pale, dense, and fibrotic, and the pancreatic duct is dilated from chronic obstruction. The white marker indicates the opening of the pancreatic duct into the duodenum where a pancreatic stone (removed) obstructed the lumen.

Figure 13.9 Complications of chronic pancreatitis

DIABETES Diabetes mellitus is not a single disease entity. Euglycemia, prediabetes, diabetes Type I diabetes is an autoimmune disease. 10% of cases, less genetic influence, normal peripheral cell insulin sensitivity, rapid teen onset, decreased beta cells, low blood insulin, not obese, difficult glucose control, ketoacidosis common Type II diabetes is a multifactorial disease. 90% of cases, more genetic influence, decreased peripheral cell insulin sensitivity, slow adult onset, obese, normal beta cells, normal to high blood insulin, glucose control easier, ketoacidosis uncommon Other causes: pregnancy, steroid Rx

DIABETES—(cont.) The complications of diabetes are mainly caused by hyperglycemia. Glycoproteins >> accelerate atherosclerosis, cause diabetic microangiopathy, retinal and kidney disease The diagnosis of diabetes should be made according to established criteria. Treatment of diabetes depends on calorie and insulin management.

Figure 13.10 Comparison of age distribution in Type I and Type II diabetes diabetes. The figure shows the age at onset and relative numbers of new cases of both types of diabetes. Type II diabetes appears much later and is much more common than Type I.

Table 13.1 Diabetes Types I/II Compared

Figure 13.11 The pathogenesis of Type I diabetes Figure 13.11 The pathogenesis of Type I diabetes. Type I diabetes is caused by autoimmune destruction of beta cells, which is induced by some type of environmental insult in genetically susceptible people.

Figure 13.12 The pathogenesis of Type II diabetes Figure 13.12 The pathogenesis of Type II diabetes. The primary mechanisms are peripheral tissue resistance to the effect of insulin, beta-cell inadequacy, and strong genetic susceptibility.

Figure 13.13 Metabolic derangements in diabetes Figure 13.13 Metabolic derangements in diabetes. Insulin deficiency prevents tissue metabolism of glucose and liver storage of glucose as glycogen; hyperglycemia is the result. Instead of glucose, tissues burn fat, which produces a large amount of acid. Excess glucose spills into urine and carries water with it; dehydration is the result. Either severe dehydration or excessive amounts of acid can cause diabetic coma.

Figure 13.14 Long-term complications of diabetes

Figure 13.15 Diabetic nephrosclerosis Figure 13.15 Diabetic nephrosclerosis. A. Normal kidney. B. Diabetic nephrosclerosis. Note the small size of the diseased kidney.

Figure 13.16 Diabetic retinopathy Figure 13.16 Diabetic retinopathy. Funduscopy of the right eye.

PANCREATIC NEOPLASMS Cystic neoplasms are uncommon and usually benign. Pancreatic carcinoma is common and lethal. Islet cell tumors are usually benign and functional.

Figure 13.17 Pancreatic carcinoma Figure 13.17 Pancreatic carcinoma. This example is in the tail of the gland; most occur in the head.

Figure 13.18 Complications of carcinoma of the pancreas