Pancreatitis: An Overview of its Pathophysiology and Diagnostic Tests

Pancreatitis: An Overview of its Pathophysiology and Diagnostic Tests 

By: Zara Saad

Abstract 

Pancreatitis is a condition caused by the inflammation of the pancreas; it is characterized by swelling that results from the immune system’s activity. This inflammation can lead to discomfort, changes, and pain in the functioning of the affected organ or tissues. It may occur when digestive enzymes or juices begin to attack the pancreas itself. The objective of this article is to enhance the understanding of the pathophysiology of pancreatitis. Additionally, it will investigate the diagnostic assessments conducted on patients suspected of having this condition. 

Introduction 

1. Anatomy and Functions of the Pancreas

The pancreas is a vital glandular organ that plays a crucial role in the overall functioning of the body [1]. It is situated posterior to the stomach, on the left side of the abdominal cavity, and is in proximity to the initial segment of the small intestine, known as the duodenum. Anatomically, the pancreas is categorized into three sections: the head, body, and tail. The pancreatic parenchyma has a lobular structure and consists of  a significant number of secretory vesicles- they constitute approximately 80–85% of the organ's total mass. The discharge ducts are essential for the pancreas's functionality. Each vesicle is equipped with an efferent duct that interconnects with others. They ultimately lead to the main duct. This principal duct, referred to as the pancreatic duct, originates in the tail of the pancreas, extends along the entire length of the organ, and culminates in the duodenum at the greater papilla. Additionally, there exists an accessory pancreatic duct, which connects to the pancreatic duct in about 70% of individuals. The substances secreted by the pancreas are conveyed through both ducts to the greater duodenal papilla [2].

The pancreas serves two critical roles within the body: its endocrine function, which involves the production of hormones that regulate blood glucose levels and glandular secretions, and its exocrine function, which pertains to its role as a digestive gland[2][3].

The endocrine function is carried out by the islets of Langerhans, which produce hormones including insulin, proinsulin, amylin, C-peptide, somatostatin, pancreatic polypeptide (PP), and glucagon. Insulin is responsible for reducing blood sugar levels, while glucagon acts to increase them. Conversely, the exocrine function encompasses the synthesis of enzymes that constitute the iso-osmotic, alkaline pancreatic juice, facilitating the digestion of food within the intestines. The acinar cells generate the enzymatic components of this juice, which is transported to the duodenum via the pancreatic ducts. Additionally, goblet cells secrete mucus within the pancreatic ducts. The composition of pancreatic juice comprises enzymes that break down proteins, fats, carbohydrates, and nucleic acids, along with electrolytes and a minor quantity of mucus[2].

2. Types and Causes of Pancreatitis 

Pancreatitis refers to the inflammation of the pancreas, which can manifest as either acute or chronic. Acute pancreatitis is characterized by a sudden onset of inflammation that persists for a brief period, allowing the pancreas to recover afterward. However, recurrent episodes of acute pancreatitis may progress to chronic pancreatitis, which can result in significant complications, and can even be fatal in severe instances. Chronic pancreatitis, on the other hand, is a prolonged form of inflammation that fluctuates over time, leading to irreversible damage to the pancreas. This condition often results in scarring of the pancreatic tissue and, in severe cases, may impair the pancreas's ability to produce essential enzymes and insulin[4].

Pancreatitis is typically not attributed to infectious agents; rather, it is often instigated by etiological factors such as gallstones and excessive alcohol intake[5]. Gallstones, which are formed in the gallbladder, may dislodge and obstruct the bile duct, preventing pancreatic enzymes from reaching the small intestine and causing them to reflux into the pancreas. This reflux leads to irritation of pancreatic cells, resulting in the inflammation which is characteristic of pancreatitis[4]. Additionally, intricate interactions between genetic and environmental factors may influence the onset and progression of the disease. Other potential causes of pancreatitis include abdominal trauma or surgical procedures, elevated levels of triglycerides in the bloodstream, high calcium levels, certain medications like estrogens, steroids, and thiazide diuretics, infections such as mumps, hepatitis A or B, and salmonella, as well as conditions like cystic fibrosis, tumors, or specific genetic abnormalities[1][5].

Pathophysiology 

1. Acute Pancreatitis  

The two primary types of acute pancreatitis are alcoholic and biliary forms[7]. In biliary acute pancreatitis, a temporary blockage of the common bile duct due to impacted stones can lead to a reflux into the pancreatic duct. This reflux increases the permeability of the duct and allows cytotoxic substances to leak into the surrounding tissues. Consequently, this results in compartmental disturbances and improper activation of enzymes within pancreatic cells.

In alcoholic pancreatitis, long-term cellular injury, obstruction of pancreatic ducts, and heightened ductal permeability with the leakage of harmful agents significantly contribute to its pathophysiology. Chronic pancreatitis often develops as a result of prolonged alcohol abuse. Once initiated by various etiological factors, the pathophysiological processes of acute pancreatitis may follow a similar trajectory. Digestive enzymes become activated and are released into intracellular, intraductal, and interstitial spaces. Trypsin, recognized as the key enzyme in the activation cascade, is believed to play a crucial role. Furthermore, lipolytic enzymes may also participate in the pathophysiological mechanisms. Phospholipase A is known to generate lysolecithin, which can damage cellular membranes.[6][7].

2. Chronic Pancreatitis 

Chronic pancreatitis (CP) is a persistent inflammatory condition of the pancreas, marked by the gradual fibrotic destruction of the pancreatic secretory tissue. Although the underlying causes and risk factors vary, mechanisms such as necrosis, apoptosis, inflammation, and duct obstruction play significant roles in the disease's progression. This fibrotic process ultimately results in a progressive deterioration of the pancreas's lobular structure and morphology, distortion of the major ducts, and significant alterations in the arrangement and composition of the islets. Consequently, these changes lead to irreversible morphological and structural damage, impairing both exocrine and endocrine functions[8][9].

Tropical chronic pancreatitis is an idiopathic, juvenile, non-alcoholic variant of chronic pancreatitis that is notably prevalent in the developing regions of the tropics. This form can be categorized into two distinct classifications: tropical calcific pancreatitis and fibrocalculous pancreatic diabetes. Tropical calcific pancreatitis represents the early pre-diabetic phase of the condition, primarily affecting younger individuals. It is characterized by intense abdominal pain, pancreatic calcification, and indications of pancreatic dysfunction, with no diabetes mellitus present at the time of diagnosis. In contrast, fibrocalculous pancreatic diabetes signifies the advanced diabetic stage of the disease. Research has indicated that the etiology of both tropical calcific pancreatitis and fibrocalculous pancreatic diabetes is associated with genetic mutations in the SPINK1 gene; however, the potential impact of environmental factors remains uncertain[8].

Diagnostic Tests and Evaluation

Accurate diagnostic techniques and the proper evaluation of the severity of acute pancreatitis are crucial for selecting an appropriate treatment approach and forecasting the clinical progression of the condition[10]. This process is essential in averting potentially life-threatening complications and preventing organ dysfunction or failure. As per established guidelines, the diagnosis of acute pancreatitis relies on blood tests to measure serum lipase and amylase levels, along with imaging modalities such as magnetic resonance cholangiopancreatography (MRCP), computed tomography (CT), and ultrasound (US)[1][10][11].

1. Laboratory Tests

Currently, the most relevant laboratory tests utilized in diagnosing acute pancreatitis (AP) include serum lipase and serum amylase [10][. Research indicates that serum lipase serves as a more dependable marker for AP compared to serum amylase. Additionally, urinary strip tests for trypsinogen-2 and trypsinogen activation peptide (TAP) provide a reliable means for early diagnosis of AP. Other enzymes, such as pancreatic isoamylase, immunoreactive trypsin, chymotrypsin, and elastase, do not surpass lipase in diagnostic efficacy and are often more cumbersome and costly. The assessment of these enzymes should be limited to cases where the diagnosis remains uncertain. It is important to note that neither enzyme’s quantity correlates with the severity of AP nor can they accurately forecast the subsequent clinical trajectory of the patient[10][12].

2. Ultrasonography

Gallstones and alcohol consumption account for approximately 70–80% of acute pancreatitis cases. Differentiating these etiologies is crucial due to their distinct management approaches. Ultrasonography is the primary imaging technique employed for all patients suspected of having acute pancreatitis, owing to its accessibility, cost-effectiveness, and lack of radiation exposure. This imaging method is particularly useful in diagnosing acute biliary pancreatitis, helping to rule out alcohol as the primary cause. It facilitates the evaluation of the biliary tract and the identification of biliary stones within the common bile duct (CBD)[13].

3. Endoscopic Ultrasound (EUS)

Endoscopic ultrasound (EUS) is a refined version of standard ultrasound that offers minimal invasiveness and high precision. It is the preferred method for examining the pancreas and biliary tract. For acute pancreatitis, EUS is employed to determine the underlying etiological cause of the condition following the decline of the acute episode. However, its application during the time the patient is hospitalized appears to be uncommon.

4. Computed Tomography 

Computed Tomography (CT) can be used as a diagnostic tool for pancreatitis. It is used to determine the severity of the condition and to identify any complications. This is an imaging technique which is highly regarded for its quick scanning capabilities and excellent spatial resolution. These qualities make it effective in detecting pancreatitis, identifying local complications and evaluating the inflammation’s intensity, hence providing an insight to the overall severity of the condition[1][10]. 

5. Magnetic Resonance Imaging 

Magnetic Resonance Imaging (MRI) and Magnetic Resonance Cholangiopancreatography (MRCP) are employed for the non-invasive assessment of the pancreatic and biliary systems. These technologies are instrumental in elucidating the causes of pancreatitis. They have several benefits which include the absence of exposure to radiation, no requirement for a contrast agent and no need for premedication. Furthermore, there’s minimal risk of complications and scans can be conducted during an episode of acute pancreatitis particularly[10]. 

Conclusion

Pancreatitis can be a severe condition but with the proper treatment, it can be overcome. It is imperative both as a preventative and curative measure to reduce the excessive intake of alcohol so the chances of developing pancreatitis are minimised. Patients may also opt for gallbladder or gallstone removal surgery.

References

1. https://www.hopkinsmedicine.org/health/conditions-and-diseases/pancreatitis#:~:text=Pancreatitis%20is%20the%20swelling%20(inflammation,The%20pancreas%20is%20a%20gland.

2. https://pmc.ncbi.nlm.nih.gov/articles/PMC9005876/ - Pancreas—Its Functions, Disorders, and Physiological Impact on the Mammals’ Organism by Monika Karpińska 1,*, Marian Czauderna

3. Yamada T., Hasler W. L., Inadomi J. M. (2005). “Structural anomalies and hereditary diseases of the pancreas,” in Gastroenter-ology, ed. Yamada Y. (Philadelphia, PA: Lippincott Williams & Wilkins; ), 80–90. [Google Scholar]

4. https://www.mayoclinic.org/diseases-conditions/pancreatitis/symptoms-causes/syc-20360227 

5. https://pmc.ncbi.nlm.nih.gov/articles/PMC6514487/-Etiology and Risk Factors of Acute and Chronic Pancreatitis by Frank Ulrich Weiss 1,*, Felix Laemmerhirt 1, Markus M Lerch 

6. https://pubmed.ncbi.nlm.nih.gov/8119636/#:~:text=The%20pathophysiology%20of%20acute%20pancreatitis,an%20activation%20of%20pancreatic%20enzymes. - Glasbrenner B, Adler G. Pathophysiology of acute pancreatitis. Hepatogastroenterology. 1993 Dec;40(6):517-21. PMID: 8119636.

7. https://pubmed.ncbi.nlm.nih.gov/2205058/ - [Pathophysiology of acute pancreatitis] by R Lüthen 1, C Niederau

8. https://pmc.ncbi.nlm.nih.gov/articles/PMC3831204/#B3 - Pathophysiology of chronic pancreatitis by Christina Brock 1,2, Lecia Møller Nielsen 1,2, Dina Lelic 1,2, Asbjørn Mohr Drewes 1,2

9. https://pubmed.ncbi.nlm.nih.gov/17351799/ - The M-ANNHEIM classification of chronic pancreatitis: introduction of a unifying classification system based on a review of previous classifications of the disease by Alexander Schneider 1, J Matthias Löhr, Manfred V Singer

10. https://pmc.ncbi.nlm.nih.gov/articles/PMC9406704/ - Diagnosis and Treatment of Acute Pancreatitis by Julia Walkowska 1, Nicol Zielinska 1, R Shane Tubbs 2,3,4,5,6,7, Michał Podgórski 8, Justyna Dłubek-Ruxer 8, Łukasz Olewnik 1,*

11. https://pmc.ncbi.nlm.nih.gov/articles/PMC4814287/ - Clinical practice guideline: management of acute pancreatitis by Joshua A Greenberg 1, Jonathan Hsu 1, Mohammad Bawazeer 1, John Marshall 1, Jan O Friedrich 1, Avery Nathens 1, Natalie Coburn 1, Gary R May 1, Emily Pearsall 1, Robin S McLeod 1,✉

12. https://pubmed.ncbi.nlm.nih.gov/16024009/ - Clinical laboratory assessment of acute pancreatitis by Ahmed Z Al-Bahrani 1, Basil J Ammori

13. https://pubmed.ncbi.nlm.nih.gov/11037420/ - Evaluation of patients with acute right upper quadrant pain. American College of Radiology. ACR Appropriateness Criteria by R L Bree 1, P W Ralls, D M Balfe, D J DiSantis, S N Glick, M S Levine, A J Megibow, S Saini, W P Shuman, F L Greene, L A Laine, K Lillemoe