Inflammation of the Pancreas: Causes

  • Blood type – blood type B (1.53-fold increased risk of chronic pancreatitis; this is due to increased serum lipase activity (1.48-fold)).

Pathogenesis (disease development)

It is believed that the inflammatory process is triggered and maintained by autodigestion (self-digestion) of the organ by enzymes such as trypsinogen, chymotrypsinogen, proelastase and others. In this process, a so-called reaction cascade takes place – enzymes activate each other. Acute pancreatitis (AP) is a sudden onset inflammation that causes edema of the pancreas and consequent cellular damage, which leads to the release of digestive enzymes. These then in turn lead to edema as well as necrosis (tissue death). Further activation of e.g. kallikrein can lead to shock symptoms, which further worsens the clinical picture. Exocrine pancreatic insufficiency (EPI; disease of the pancreas associated with insufficient production of digestive enzymes), resulting in maldigestion (“poor digestion”) with diarrhea (diarrhea), steatorrhea (fatty stools), weight loss, and micronutrient (vital substance) deficiencies, may occur after acute pancreatitis; after chronic pancreatitis, the time of onset is unpredictable. After 10 years, exocrine insufficiency occurs in more than half of chronic pancreatitis patients and after 20 years in almost all patients (more than half of the organ must be destroyed for steatorrhea to occur; occurs only when lipase secretion is reduced by more than 90-95%). Chronic pancreatitis is the sequelae of inadequately treated acute pancreatitis. In turn, various forms can be distinguished, such as pancreatitis with circumscribed necrosis or diffuse fibrosis (pathological proliferation of connective tissue). Chronic pancreatitis leads to exocrine pancreatic insufficiency (see above) and endocrine pancreatic insufficiency, i.e., insulin deficiency diabetes.

Etiology (Causes)

Causes of pancreatitis at a glance:

  • Acute pancreatitis:
  • Chronic pancreatitis – 70-90% of cases chronic alcohol abuse.
  • Less common causes of pancreatitis are:
    • Genetic stress:
      • Genes associated with chronic pancreatitis (very rare):
        • PRSS1: cationic trypsinogen.
        • CFTR: “Cystic fibrosis transmembrane conductance regulator”
        • SPINK1: serine protease inhibitor, Kazal type 1.
        • CTRC: chymotrypsinogen C
        • CPA1: carboxypeptidase A1
      • Hereditary pancreatitis (autosomal dominant inheritance with variable expressivity and an incomplete penetrance; very rare).
      • Pancreas divisum (most common congenital malformation of the pancreas; can be detected on endoscopic retrograde cholangiopancreaticography (ERCP) in 7.5-10% of cases); approximately 5% develop symptoms; there are three different variants:
        • Complete pancreatic divisium (70% of cases): both pancreatic ducts are separated from each other; drainage of pancreatic secretion (pancreatic secretion) occurs almost exclusively via the minor papilla (small mucosal elevation in the descending part of the duodenum, where the additional duct of the pancreas opens)
        • Incomplete pancreas divisum (20% of cases): there is still a small caliber connecting duct between ductus pancreaticus major and minor (pancreatic duct).
        • Reverse pancreas divisum (10% of cases): there is a complete pancreas divisum, in which the dorsal and ventral plant are mirrored horizontally; Ductus pancreaticus minor (small pancreatic duct) opens here via the major papilla.
    • Metabolic disorders:
    • Viral infections e.g. hepatitis, mumps.
    • Papillary obstruction (eg, papillary stenosis, duodenal obstruction).
    • Parasites (e.g., ascariasis, echinococcus).
    • Trauma injuries, accidents), e.g., surgical trauma.

Biographical causes

  • Genetic alterations (30-35% of cases).
    • Mutations of CFTR (cystic fibrosis transmembrane conductance regulator), SPINK (serine protease inhibitor type Kasal), or chymotrypsin C.
    • Hereditary (inherited) form of pancreatitis (1% of cases) – autosomal dominant disease, heterozygous mutations in the cationic trypsinogen (PRSS1) gene on chromosome 7 (penetrance: -80%) or the serine protease inhibitor (SPINK1) gene or the pancreatic secretory trypsin inhibitor (PSTI) gene on chromosome 5 [affect chronic pancreatitis].
    • Genetic disorders
      • Hemochromatosis (iron storage disease): congenital or hereditary hemochromatosis (HH; primary hemochromatosis) – genetic, autosomal recessive inheritance (4 (5) types are now distinguished, with type 1 (mutation in the HFE gene) being the most common in Europe: 1: 1,000); may lead to chronic pancreatitis
      • Cystic fibrosis (ZF) – genetic disease with autosomal recessive inheritance, characterized by the production of secretions in various organs to be tamed.
  • Malformations
    • Pancreas divisum – congenital “divided” pancreas (see “Causes of pancreatitis at a glance” above for details).
    • Strictures (high-grade stenosis (narrowing) of the lumen of a hollow organ) of the pancreas
    • Duodenal diverticulum – congenital outpouching of the duodenum.
  • Blood type – blood type B (1.53-fold increased risk of chronic pancreatitis; the reason is increased activity of serum lipase (1.48-fold)).
  • Pregnancy – can lead to fatty liver, among other things. However, pancreatitis can also occur in an uncomplicated pregnancy and is then usually associated with gallstone disease

Behavioral causes

  • Nutrition
  • Pleasure food consumption
    • Alcohol* (alcohol abuse/abuse; > 80 g alcohol/day for 6-12 years).
    • Tobacco (smoking):
      • Possibly increases the risk of acute pancreatitis
      • Increases the risk for chronic pancreatitis and accelerates progression (progression) of the disease
  • Blunt abdominal trauma – e.g., impact to the abdomen – important risk factor, especially in children.
  • Overweight (BMI ≥ 25; obesity) – is not only a risk factor in the development of local (local) and systemic complications, but also increases mortality

Disease-related causes

  • Bacterial infections such as mycoplasma, campylobacter, leptospires, legionella, mycobacterium tuberculosis, mycobacterium-avium complex.
  • Cholecystolithiasis* (gallstone disease).
  • Chronic renal insufficiency
  • Ulcerative colitis – chronic inflammatory bowel disease (colon and rectum).
  • Diabetes mellitus
  • Enteritis (inflammation of the intestine)
  • Hemolytic uremic syndrome (HUS) – triad of microangiopathic hemolytic anemia (MAHA; form of anemia in which erythrocytes (red blood cells) are destroyed), thrombocytopenia (abnormal decrease in platelets/platelets), and acute kidney injury (AKI); Mostly occurring in children in the context of infections; most common cause of acute renal failure requiring dialysis in childhood.
  • Helminthiasis (worm diseases): askaris, clonorchis; cause obstructive pancreatitis (e.g., obstruction of the bile duct)
  • Hepatitides – viral inflammation of the liver.
  • Hypercalcemia (calcium excess), primary or secondary.
  • Hyperlipoproteinemia (dyslipidemia) – Hypertriglyceridemia (serum triglyceride concentration > 200 mg/dl).
  • Hyperparathyroidism (hyperparathyroidism), primary – leads to hypercalcemia (calcium excess).
  • Hypothermia shock, hypoxia – lack of oxygen in shock.
  • Kawasaki syndrome – acute, febrile, systemic illness characterized by necrotizing vasculitis (vascular inflammation) of small and medium-sized arteries.
  • Collagenoses and vasculitides (vascular inflammation) – for example, in systemic lupus erythematosus, necrotizing angiitis.
  • Crohn’s disease – chronic inflammatory bowel disease; it usually runs in relapses and can affect the entire digestive tract; characteristic is the segmental affection of the intestinal mucosa (intestinal mucosa), that is, it may be affected several intestinal sections that are separated by healthy sections from each other
  • Cystic fibrosis (cystic fibrosis) – genetic defect, which is manifested mainly by the production of too viscous mucus.
  • Papillary obstruction (e.g., papillary stenosis, duodenal obstruction, periampullary carcinoma/as periampullary carcinomas, pancreatic head carcinoma, cholangiocellular carcinoma (CCC, cholangiocarcinoma, bile duct carcinoma, bile duct cancer) and ampullary carcinoma are summarized).
  • Parasites in bile ducts, such as ascariasis, echinococcus, clonorchiasis.
  • Purpura Schönlein-Henoch
  • Reye syndrome – acute encephalopathy (pathological change of the brain) with concomitant fatty liver hepatitis (fatty liver inflammation) after a passed viral infection in young children; occurs on average one week after the previous illness has resolved
  • Ulcus duodeni (duodenal ulcer).
  • Vasculitis – inflammatory rheumatic diseases characterized by a tendency to inflammation of the (mostly) arterial blood vessels.
  • Viral infections such as mumps, rubella, hepatitis A, B, C, Coxsackie B virus, echoviruses, adenovirus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), human immunodeficiency virus (HIV).

* Main risk factors – Alcohol abuse and gallstone disease together cause approximately 70-80% of all acute pancreatitis (inflammation of the pancreas). Laboratory diagnoses – Laboratory parameters that are considered independent risk factors.

  • Apolipoprotein CII deficiency
  • Hypercalcemia (calcium excess)
  • Hypertriglyceridemia: risk increases for acute pancreatitis (reference value: nonfasting triglyceride level < 89 mg/dl (1 mmol/l)):
    • + 60% at 89-176 mg/dl (1.00-1.99 mmol/l).
    • + 130 % at 177-265 mg/dl (2.00-2.99 mmol/l)
    • + 190 % at 266-353 mg/dl (3.00-3.99 mmol/l)
    • + 290 % at 354-442 mg/dl (4.00-4.99 mmol/l)
    • + 770 % at ≥ 442 mg/dl (≥ 5.00 mmol/l)

Medications

The following is a list of medications that can lead to pancreatitis [very rare! : 0.05% of cases] (No claim to completeness! ):

* Correlation probable * * Possible causal relationship.

Operations – Investigations

  • Abdominal surgery – postoperative pancreatitis, e.g., after gastric resection (surgical removal of part of the stomach).
  • Intraoperative endoscopic examinations – reflection of the biliary & pancreatic ducts, e.g., after ERCP (endoscopic retrograde cholangiopancreaticography); papillotomy (cleavage of the papilla duodeni major together with the sphincter apparatus/sphincter apparatus (sphincter oddi)); pancreatic biopsy (tissue sampling from the pancreas).
  • Condition after kidney transplantation – pancreatitis develops in about 3% of kidney transplant recipients.

Environmental exposure – intoxications (poisonings).

  • Organophosphates (e.g. E605)

In the Anglo-Saxon world, the mnemonic “I GET SMASHED” is used to memorialize the triggers of pancreatitis, an acronym for: I: idiopathic, G: gallstones, E: ethanol, T: trauma, S: steroids, M: mumps, A: autoimmune, S: scorpion toxin, H: hypercalcemia, hypertriglyceridemia, E: ERCP, D: drugs.