Pancreatic Parameters

The pancreas is a composite organ containing a distinctive combination of cell lineages. The exocrine tissue comprises acinar cells, which secrete digestive enzymes into the intestine. The endocrine function is performed by the islets of Langerhans, which consist of distinct cell types secreting 4 different hormones into the circulation (α-cells, glucagon; β-cells, insulin; δ-cells, somatostatin; and γ-cells, pancreatic polypeptide). Endocrine hormones, as well as some exocrine enzymes, can be measured in body fluids and provide important diagnostic information in acute and chronic pancreatic disease.

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Overview

Pancreas

The pancreas is an organ positioned across the posterior aspect of the abdomen, behind the stomach and has 2 major functions:

  • Endocrine: islets of Langerhans
  • Exocrine: performed by structures made of the acini and intercalating ducts 
The pancreas

The pancreas

Image: “The pancreas” by CDC. License: CC BY 3.0

Endocrine pancreas physiology

The islets of Langerhans, scattered throughout the pancreas, have different types of cells, which correspond to the following hormones:

  • Insulin (originating from B cells or β-cells)
  • Glucagon (originating from A cells or α-cells)
  • Somatostatin (originating from D cells or δ-cells)
  • Pancreatic polypeptide (originating from PP cells or γ-cells)

Functions and stimuli differ with each hormone.

Exocrine pancreas physiology

  • Digestive activity
  • Production of pancreatic enzymes and bicarbonate
  • Enzymes:
    • Amylase (digestion of carbohydrates/starch)
    • Lipases (digestion of fats):
      • Lipase
      • Phospholipase A2
      • Nonspecific esterase
    • Proteases (stored as inactive forms/proenzymes to prevent autodigestion):
      • Trypsinogen → trypsin (digests proteins and activates other proenzymes)
      • Proelastase → elastase (digests connective tissue, particularly elastin)
      • Chymotrypsinogen → chymotrypsin (digests proteins)
      • Procarboxypeptidase → carboxypeptidase (digests proteins)
    • Nucleases (degrade nucleic acids):
      • DNase
      • RNase
  • Regulation:
    • Cholecystokinin: 
      • Stimulates acinar secretion
      • Triggered by gastric acid, long-chain fatty acids, and essential amino acids
    • Secretin:
      • From S cells of duodenal mucosa
      • Release stimulated by gastric acid/decline in pH (< 4.5), prompting production and secretion of bicarbonate
  • Inhibitory neuropeptides:
    • Somatostatin
    • Pancreatic polypeptide, peptide YY,  neuropeptide Y
    • Enkephalin
    • Pancreastatin
    • Calcitonin gene-related peptide
    • Glucagon

Endocrine Pancreas

Insulin

  • Released from B cells with C peptide (detaches before insulin secretion)
  • Hormonal effects:
    • Promotes absorption of glucose from the blood into liver, fat, and skeletal muscle cells
    • Regulates the metabolism of carbohydrates, fats, and protein
  • Associated tests: 
    • Serum C peptide:
      • Gives an index of B cell function
      • A low level indicates low endogenous-insulin production.
    • Serum insulin:
      • ↓ In type 1 diabetes mellitus (autoimmune destruction of β-cells, which leads to an almost complete lack of insulin)
      • ↓ In type 2 diabetes mellitus (nonautoimmune destruction of β-cells, which causes partial insulin deficiency)
      • ↑ In insulinoma (pancreatic tumor producing insulin)
      • ↑ In insulin resistance (metabolic syndrome)
      • ↑ In β-islet cell hypertrophy
      • ↑ In congenital hyperinsulinism

Somatostatin

  • Also known as growth hormone-inhibiting hormone
  • Produced in the CNS
  • Hormone functions are generally inhibitory on the following:
    • Endocrine and exocrine secretion
    • Neurotransmission and cell proliferation 
    • GI motility
  • Associated test is plasma somatostatin:
    • Increased levels in the following condition or situation:
      • Somatostatinoma (triad of diabetes, cholelithiasis, and diarrhea/steatorrhea)
      • Other neuroendocrine tumors
      • Similar stimuli increase insulin secretion (glucose and amino acids)
    • Decreased levels in chronic gastritis (persistent Helicobacter pylori infection)

Glucagon

  • Peptide hormone produced by the pancreas in response to hypoglycemia
  • Inhibited by insulin, somatostatin, and secretin
  • Hormonal effects (generally to increase glucose levels):
    • Promotion of glycogenolysis 
    • Promotion of neoglucogenesis
    • Inhibition of hepatic glycogenesis
  • Associated test is plasma glucagon:
    • Increased in the following conditions:
      • Glucagonoma (migratory erythema, glucose intolerance, anemia, and malnutrition)
      • Glucagonoma as a part of multiple endocrine neoplasia (MEN) type 1
      • Diabetes mellitus
      • Stress-related conditions (e.g., sepsis, acute myocardial infarction, trauma, acute pancreatitis, burns)
      • Renal failure
      • Hepatic cirrhosis or hepatocellular carcinoma
    • Decreased levels in pancreatectomy

Pancreatic polypeptide

  • Synthesized and secreted by PP cells (also known as F cells or γ-cells) of the pancreas
  • Hormonal effects: 
    • Inhibition of pancreatic exocrine secretion, gallbladder contraction, and gut motility 
    • May influence food intake by regulating hunger and satiety
  • Secretion increased via vagal stimulation:
    • Following a protein meal
    • Fasting
    • Exercise
    • Hypoglycemia
  • Secretion decreased by:
    • Somatostatin
    • IV glucose
  • Associated test is plasma pancreatic polypeptide:
    • Increased in the following conditions:
      • Anorexia nervosa
      • Pancreatic neuroendocrine tumors
    • Decreased in the following conditions:
      • Chronic pancreatitis
      • Prader-Willi syndrome and other forms of obesity

Exocrine Pancreas

Pancreatic amylase

  • Facilitates the breakdown of dietary starch into smaller polysaccharides
  • Most abundant isoforms:
    • S form (primarily salivary origin)
    • P form (derived from the pancreas)
  • Associated test is serum or plasma amylase:
    • Usual serologic tests cannot discriminate the 2 isoforms.
    • In acute pancreatitis, the level rises within 6–12 hours and normalizes within 5 days.
    • Elevated in the following conditions:
      • Acute pancreatitis (strong indicator if > 3x more than normal value)
      • Complications of pancreatitis (pseudocysts, abscess)
      • Other pancreatic conditions: trauma, surgery, carcinoma
      • Endoscopic retrograde cholangiopancreatography
      • Cystic fibrosis
      • Salivary pathology
      • GI pathology (intestinal perforation/obstruction)
      • Ectopic pregnancy
      • Macroamylasemia (amylase bound to macromolecules)
      • Drugs (salicylates, estrogens, thiazides, sulfonamides)
      • Renal failure (amylase is eliminated by the kidneys)

Pancreatic lipase

  • Hydrolyzes triglycerides into glycerol and free fatty acids
  • Activity is inhibited by bile acids. 
  • Requires the presence of another enzyme, colipase, which prevents bile salts from causing deactivation
  • Associated test is serum lipase:
    • Longer half-life than amylase (up to 14 days to normalize) due to renal reabsorption
    • In acute pancreatitis, increase is noted within 4–8 hours.
    • Elevated in all pancreatic conditions with increased amylase
    • Predominant increase in lipase can be seen in:
      • Alcoholic pancreatitis
      • Acute on chronic pancreatitis (normal amylase due to depletion of gland)
      • Delayed presentation of acute pancreatitis (due to longer half-life)
      • Hypertriglyceridemia-induced pancreatitis

Pancreatic elastase (elastase-1)

  • Belongs to the family of serine proteases
  • Sensitive and specific test for pancreatic function:
    • Remains undegraded or stable during intestinal transit
    • Stool levels reflect pancreatic exocrine function and directly correlate with concentration in the pancreatic fluid.
  • Associated test is fecal elastase-1:
    • A fecal elastase-1 test < 200 μg/g is abnormal.
    • Elevated in acute pancreatitis 
    • Decreased levels in chronic exocrine pancreatic insufficiency due to:
      • Cystic fibrosis
      • Chronic pancreatitis

Other tests

  • Serum trypsinogen: 
    • Sensitive test for advanced exocrine insufficiency (↓ levels)
    • Less reliable in mild exocrine insufficiency 
    • Can increase in acute pancreatitis and other nonpancreatic, abdominal pathology
  • Fecal chymotrypsin: 
    • Less sensitive and specific than fecal elastase-1
    • Decreased sensitivity for mild exocrine insufficiency
    • Can be diluted in the case of diarrhea

Clinical Relevance

  • Acute pancreatitis: an inflammatory disease of the pancreas due to autodigestion. Acute pancreatitis is commonly associated with gallstones and excessive alcohol use. Patients typically present with epigastric pain, which radiates to the back. Diagnosis requires 2 of the following 3 criteria: characteristic abdominal pain, characteristic radiology findings, and serum amylase and lipase 3x the upper limit of normal. Management includes aggressive IV hydration, analgesia, nutritional support, and treatment of the underlying cause.
  • Chronic pancreatitis: results from persistent inflammation, fibrosis, and irreversible cell damage to the pancreas, causing a loss of endocrine and exocrine gland function. The most common etiologies are alcohol abuse and pancreatic duct obstruction. Patients often present with recurrent epigastric abdominal pain, nausea, and features of malabsorption syndrome (diarrhea, steatorrhea, and weight loss). Characteristic CT findings include pancreatic atrophy, dilated pancreatic ducts, and pancreatic calcifications. Therapy focuses on alcohol cessation, dietary changes, pain management, and treatment of pancreatic insufficiency.
  • Cystic fibrosis: an autosomal recessive, hereditary disease of the exocrine glands affecting primarily the lungs and digestive system due to a spectrum of defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The mutation leads to an inability to properly transport chloride. The result is dehydrated, thick, viscus mucus, which obstructs mucus glands in the affected organs and systems. Pancreatic insufficiency is one of the presenting features of cystic fibrosis.

References

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  2. Barrett, K.E., & Barman, S.M., & Brooks, H.L., & Yuan, J.J.(Eds.), (2019). Endocrine functions of the pancreas & regulation of carbohydrate metabolism. Ganong’s Review of Medical Physiology, 26e. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2525&sectionid=204296197
  3. Bliss, E.S., Whiteside, E. (2018). The Gut-Brain Axis, the Human Gut Microbiota and Their Integration in the Development of Obesity. Front Physiol. 9:900. doi: 10.3389
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