L7 Pancreas

1. Pancreas Overview

• Location and Structure:

  • Abdominal organ, located behind the stomach.

  • 15 cm long, divided into head, body, and tail.

  • Head: Located in the curvature of the duodenum.

  • Body: Longest part.

  • Tail: Ends near the spleen.

• Ducts:

  • Main Pancreatic Duct: Joins the common bile duct to form the hepatopancreatic ampulla, which opens into the duodenum.

  • Accessory Pancreatic Duct: Also drains into the duodenum.

2. Pancreatic Histology

• Exocrine Pancreas:

  • Fluids secreted onto an epithelial surface

    • Acinar Cells: Secrete digestive enzymes (e.g., proteases, amylase, lipase).

    • Duct Cells: Secrete bicarbonate (HCO3−) to neutralize acidic chyme.

• Endocrine Pancreas:

  • Islets of Langerhans:

    • Alpha Cells (α): Secrete glucagon.

    • Beta Cells (β): Secrete insulin.

    • Delta Cells (δ): Secrete somatostatin.

    • PP Cells: Secrete pancreatic polypeptide

      • regulates gastric secretions

3. Pancreatic Juice

• Composition:

  • Bicarbonate (HCO3−): Neutralizes stomach acid (pH ~8).

  • Digestive Enzymes:

    • Proteases: Released as zymogens (e.g., trypsinogen activated to trypsin).

    • Amylase: Breaks down carbohydrates.

    • Lipase: Breaks down fats.

    • Nucleases: Break down nucleic acids.

• Regulation:

  • Cholecystokinin (CCK): Stimulates enzyme secretion from acinar cells.

  • Secretin: Stimulates bicarbonate secretion from duct cells.

• Pancreatic Secretion and Release

  1. Chyme Enters Duodenum:

     • Chyme (partially digested food) enters the duodenum from the stomach.

  2. Release of Hormones:

     • Cholecystokinin (CCK) and Secretin are released from duodenal enteroendocrine cells in response to chyme.

  3. Hormones Enter Bloodstream:

     • CCK and Secretin travel through the bloodstream to reach their target organs.

  4. CCK Actions:

     • Stimulates Pancreas: CCK induces the secretion of enzyme-rich pancreatic juice from acinar cells.

     • Stimulates Gallbladder: CCK causes the gallbladder to contract and the hepatopancreatic sphincter to relax, allowing bile to enter the duodenum.

  5. Secretin Actions:

     • Stimulates Pancreas: Secretin causes the secretion of bicarbonate-rich pancreatic juice from duct cells to neutralize acidic chyme.

     • Stimulates Liver: Secretin (along with bile salts) increases bile production in the liver.

  6. Vagal Nerve Stimulation:

     • During the cephalic and gastric phases, the vagus nerve causes weak contractions of the gallbladder, preparing it for bile release.

4. Functions of the Pancreas

• Insulin:

  • Produced by beta cells.

  • Functions:

    • Liver: Promotes glycogen synthesis (glycogenesis), inhibits glycogen breakdown (glycogenolysis).

    • Muscle: Increases glucose uptake and glycogen synthesis.

    • Adipose Tissue: Increases glucose uptake and fat storage.

  • Regulation: Released in response to high blood glucose levels.

• Glucagon:

  • Produced by alpha cells.

  • Functions:

    • Liver: Promotes glycogen breakdown (glycogenolysis) and gluconeogenesis.

    • Adipose Tissue: Promotes fat breakdown (lipolysis).

  • Regulation: Released in response to low blood glucose levels.

• Somatostatin:

  • Produced by delta cells.

  • Function: Inhibits the release of both insulin and glucagon.

• Pancreatic Polypeptide:

  • Produced by PP cells.

  • Function: Regulates gastric secretions and appetite.

5. Blood Glucose Regulation

• Insulin and Glucagon:

  • Counter-Regulatory Hormones: Insulin lowers blood glucose, while glucagon raises it.

  • Negative Feedback:

    • Insulin: Released when blood glucose is high; inhibits glucagon release.

    • Glucagon: Released when blood glucose is low; inhibited by insulin.

  • WHY?

    • To mobilise glycogen when glucose is needed by the muscles during stress

    • when glucose in the diet is in short supply

• Nervous System Role:

  • Parasympathetic Nervous System: Stimulates insulin release during digestion.

    • Acetylcholine is released

  • Sympathetic Nervous System: Stimulates glucagon release and inhibits insulin realease during stress or exercise.

    • Noradrenaline is released

• Other Hormones:

  • Adrenaline: Promotes glycogenolysis in the liver and muscles.

  • Cortisol: Promotes gluconeogenesis and reduces glucose utilization by cells.

6. Glucose Sensing in Beta Cells

• GLUT2 Transporter: Facilitates glucose entry into beta cells.

• Glucokinase: Phosphorylates glucose, initiating metabolism.

• ATP Production: Increased ATP closes potassium channels, leading to membrane depolarization and calcium influx, triggering insulin secretion.

7. Pancreatic Hormone Receptors

• Glucagon Receptor:

  • GPCR (G-protein coupled receptor).

  • Activates adenylate cyclase, producing cAMP, which activates protein kinase A (PKA).

• Insulin Receptor:

  • Receptor Tyrosine Kinase (RTK).

  • Phosphorylates intracellular proteins, initiating signaling pathways that promote glucose uptake and metabolism.

8. Pancreatic Diseases

• Diabetes Mellitus:

  • Affects 2% of the western population

    • Type 1 Diabetes (T1DM):

      • Cause: Autoimmune destruction of beta cells.

      • Treatment: Insulin injections.

    • Type 2 Diabetes (T2DM):

      • Cause: Insulin resistance.

        • Cells do not respond to insulin even when insulin levels are normal.

      • Treatment: Diet, exercise, and medications.

    • Gestational Diabetes (GDM):

      • Occurs during pregnancy; usually resolves after delivery.

• Diabetes Insipidus:

  • Cause: Lack of vasopressin (ADH) or kidney insensitivity to ADH.

  • Symptoms: Excessive thirst and dilute urine.

• WHY MUST INSULIN BE ADMINISTERED BY INJECTION AND NOT ORALLY?

  • Since insuline is a peptide hormone, it would would eventually be destroyed by the stomach acid and proteolytic enzymes from the small intestine if taken orally

  • It’s a large molecule that cannot be absored by the GI tract

• WHY MAY INSULIN TREATMENT ITSELF BE HAZARDOUS?

  • Risks:

    • Overdose may result in hyperglycemia (high blood sugar levels)

    • Potentially cause weight gain, since insuline promotes fat storage and glucose uptakes by the cells

    • Improper management on the long term may lead to dabetic neuropathy due to blood sugar levels fluctuations

• Hyperinsulinism:

  • Cause: Benign tumor of the pancreas.

  • Symptoms: Low blood glucose, leading to anxiety, sweating, and coma.

• Pancreatitis:

  • Causes: Gallstones, alcohol, or high triglyceride levels.

  • Symptoms: Inflammation of the pancreas, leading to severe pain.

  • Resulted in more than 100,000 deaths worldwide and increasing

• Pancreatic Cancer:

  • Types:

    • Exocrine:

      • Adenocarcinoma (most common).

      • 85% of pancreatic cancers

      • starts in the pancreas head

      • Acinar cells carcinoma (5%)

        • increased production of enzymes.

    • Neuroendocrine:

      • Pancreatic neuroendocrine tumours

        • could be malignant or benign

        • could be functioning or non-functioning

      • Often diagnosed late, with low survival rates.