Pancreas Function & Chemical Pathology

Pancreas Function & Chemical Pathology

• The pancreas is an elongated, flattened pyramidal organ mostly located behind the stomach.
• The tail of the pancreas points towards the spleen, and the head is nestled in the duodenal loop.
• The pancreas is a soft, easily traumatized gland located behind the peritoneum (membrane lining the abdominal cavity).

Exocrine Secretions

• Exocrine secretions are drained through ductules that combine into a single pancreatic duct.
• In most individuals, this pancreatic duct joins the common bile duct at the Ampulla of Vater.
• The exocrine acinar cells account for more than 98% of the pancreatic mass.

Endocrine Hormones

• About 1% of the pancreas consists of clusters of cells called the islets of Langerhans.
• These cells produce the endocrine hormones.
• 1 million islets are present in the pancreas.
• Pancreatic endocrine secretions from the islets of Langerhans include the hormones: Glucagon, Insulin, Somatostatin, and Pancreatic polypeptide.

Normal Pancreatic Exocrine Secretion

• The pancreas produces at least 22 digestive enzymes, 15 of which are proteases.
• Pancreatic enzymes act on three major dietary sources of energy: proteins, lipids, and complex carbohydrates.
• The functional unit of the exocrine pancreas consists of acini that store most digestive enzymes in inactive forms (zymogens) within zymogen granules.

Proenzymes and Protease Inhibitors

• The proenzyme forms of proteolytic enzymes prevent autodigestion of the zymogen granules, acinar cells, and the pancreas itself.
• The pancreas also secretes protease inhibitors to neutralize any improperly activated enzymes.
• Congenital deficiency of trypsinogen inhibitors can cause inherited predisposition to acute pancreatitis.

Enterokinase Activation

• In the duodenum, a brush-border enzyme called enterokinase converts trypsinogen to trypsin.
• Free trypsin then activates other pancreatic proenzymes into their active forms.

Normal Pancreatic Fluid Secretion

• A normal adult secretes approximately 2 to 3 liters of pancreatic juice per day.
• This fluid contains bicarbonate ions (120-300 mmol/day).
• Pancreatic juice also contains enzymes like amylase and lipase (500,000 to 1 million U/L).

Control of Exocrine Pancreatic Secretions

• Exocrine secretions are regulated by both neural and hormonal pathways.
• Upper GI tract hormones (cholecystokinin (CCK), secretin, and gastrin) affect pancreatic juice secretion.
• Ingestion of ethanol or distention of the duodenum by chyme lead to the release of these hormones.

Pathological Conditions

• Diseases of the pancreas can be categorized into islet disorders (e.g., diabetes, glucagon excess), exocrine insufficiency, inflammatory disorders (e.g., acute/chronic pancreatitis), and neoplastic disorders (e.g., adenocarcinomas, islet cell tumors).

Endocrine Pancreatic Disorders

• Diabetes mellitus (DM) is a major endocrine disorder characterized by either inadequate insulin secretion (type 1 diabetes) or insulin resistance (type 2 diabetes).
• Pancreatic islet cell tumors often produce excessive hormones, leading to diverse clinical syndromes.

Exocrine Pancreatic Disorders

• Acute pancreatitis is an inflammatory disorder associated with activation of local pancreatic enzymes, leading to tissue destruction.
• Common causes include alcohol abuse and biliary tract obstruction (e.g., gallstones).

Inflammatory or Necrotic Pancreatic Injury

• Acute pancreatitis is a serious condition that can lead to life-threatening emergencies in severe forms.

Acute Pancreatitis Causes

• Common reasons for acute pancreatitis include alcohol abuse and biliary tract obstruction by gallstones.
• About 75% of cases of acute pancreatitis are caused by these two factors

Acute Pancreatitis Tests

• ALT above 150 U/L is a predictor for gallstone pancreatitis.
• Severity of pancreatitis is associated with elevated mortality risk.
• Serum amylase and lipase levels are used in diagnosis, but not for predicting pancreatitis severity.

CRP in Pancreatitis

• C-reactive protein (CRP) is a useful inflammatory marker to assess prognosis, but not for diagnosis.

Ranson's Criteria for Acute Pancreatitis

• These clinical criteria help predict the prognosis and mortality risk of acute pancreatitis.

Chronic Pancreatitis

• Chronic pancreatitis is a consequence of repeated acute pancreatitis, and in some cases, leads to extensive gland destruction, possibly resulting in diabetes.
• Increased serum amylase and lipase activities are seen during acute exacerbation, but between episodes, levels might be below normal (up to 60% of cases).

Cystic Fibrosis

• Cystic fibrosis is an autosomal recessive inherited disease caused by mutations in chloride transport genes.
• CFTR protein dysfunction leads to viscous, low-volume pancreatic secretions, resulting in obstruction.

Pancreatic Insufficiency

• Pancreatic exocrine function loss/reduction in the late stages manifests as severe gastrointestinal disturbances, such as diarrhea, constipation, and malabsorption leading to weight loss and a condition known as cachexia.
• Significant symptoms typically appear when about 85% to 90% of acinar tissue is lost.

Common Causes of Pancreatic Insufficiency

• In children, the most common cause is cystic fibrosis.
• In adults, chronic pancreatitis is the common cause.

Pancreatic Neoplasms

• Adenocarcinomas, arising from ductal epithelial cells, are the most common pancreatic cancers and have a poor prognosis.
• Islet cell tumors make up a small portion (1%) of pancreatic neoplasms, and their clinical features often depend on the excessive production of specific hormones.

Insulinoma

• Insulinoma, a rare but common type of islet cell tumor, produces excessive insulin, resulting in hypoglycemia.

Glucagonoma

• Glucagonomas, characterized by distinctive combinations of hyperglycemia, weight loss, and skin rashes, are tumors that produce glucagon.

Exocrine Pancreatic Tests

• Duodenal fluid analysis is the best sample to evaluate pancreatic function.
• Measurements of bicarbonate and pancreatic enzymes (especially amylase, lipase, and chymotrypsin) are possible through this method, but it is difficult to obtain.

Tests on Feces

• Stool tests are not always a reliable reflection of minor disorders of pancreatic acinar tissue, and the accuracy severely reduced after 85% to 90% loss of acinar tissue
• Tests for trypsin and chymotrypsin in stool are less sensitive. measuring elastase 1 in stool may be unreliable.

Indirect Test of Pancreatic Function

• N-benzoyl-tyrosyl-para-aminobenzoic acid (NBT-PABA) is a well-known indirect pancreatic function test.
• Pancreatic enzyme tests (e.g., amylase and lipase) in blood are used as indicators of cellular injury to the pancreas.

Change in Analytes with Disease

• Imaging studies are often used, but diagnosis is usually based on increased serum amylase, lipase, and immunoreactive trypsin.
• The gradient of amylase between the pancreas and plasma is high, making amylase a sensitive test for pancreatic injury

Amylase and Lipase

• Increased serum amylase and lipase, along with immunoreactive trypsin, are typical in pancreatitis diagnosis.
• The amylase/plasma gradient is high, thus amylase provides a sensitive marker for pancreatic injury.

Lipase

• Lipase is a more specific indicator for pancreatitis than amylase.
• Current guidelines suggest using only one of these enzymes (lipase is often preferred).

Cancer Markers

• CA19-9 is the most used tumor marker for pancreatic cancer.
• It isn't cancer-specific, and has abnormal levels with other types of biliary obstruction or conditions like cirrhosis.
• CA19-9 is helpful in evaluating patient response to treatment, especially in advanced pancreatic cancer cases.

Endocrine Tumor Markers

• Approximately 20% of islet cell tumors do not produce detectable hormones.
• These tumors can secrete hormones like Insulin, Glucagon, Gastrin, Vasoactive intestinal peptide (VIP), Adrenocorticotropic hormone, Secretin, Serotonin, and Calcitonin.

Insulin

• Insulin levels are reported as a ratio to glucose.
• A ratio above 0.3 indicates inappropriate insulin production.
• High insulin-to-glucose ratios, along with high C-peptide levels, are strong indicators of insulinoma.
• Exogenous insulin administration creates a high insulin-to-glucose ratio but undetectable C-peptide.

Glucagon

• Glucagonoma diagnosis depends on plasma glucagon measurements
• A high glucagon level (usually greater than 1000 pg/mL) is a key criterion for these tumors, though levels above 500 pg/mL may occur in other conditions like renal failure, starvation, or pancreatitis.

Explore the anatomy and functions of the pancreas, focusing on its roles in both exocrine secretions and endocrine hormone production. This quiz covers key concepts including the structure of the pancreas, its duct system, and the importance of islets of Langerhans in hormone regulation.