**Abstract**

Chronic pancreatitis is an inflammatory disease that causes irreversible anatomical changes including infiltration of inflammatory cells, fibrosis and pancreatic calcification with destruction of the structure of the gland, leading to abdominal pain, endocrine and exocrine dysfunction. Pancreatic exocrine insufficiency (PEI) prevalence in chronic pancreatitis varies between 40 and 94%. PEI is diagnosed by direct and indirect tests. Nutritional status is assessed by anthropometric indicators; laboratory tests—hemoglobin, plasma proteins (albumin, prealbumin, retinol-binding protein, transferrin), fat-soluble vitamins A, D, E, K; micronutrients. Pancreatic enzyme replacement therapy (PERT) is a fundamental part of PEI treatment. An optimal PERT could prevent serious PEI complications such as metabolic bone disease, adverse cardiovascular events, cachexia, poor quality of life and mortality. A periodic screening for PEI complications with a respect to their primary and secondary prophylaxis is mandatory. Diabetes mellitus secondary to pancreatic disease is defined as pancreatogenic diabetes or type 3c diabetes mellitus. Patients with chronic pancreatitis are at increased risk for pancreatic cancer influenced by smoking, alcohol abuse, chronic inflammation and pancreatic stellate cells over-proliferation. However, chronic pancreatitis could be further complicated with splenic vein thrombosis, pseudocysts, duodenal or biliary obstruction, pseudoaneurysm and pancreatic duct stones which might require endoscopic or surgical treatment.

**Keywords:** chronic pancreatitis, pancreatic exocrine insufficiency, enzyme replacement therapy, pancreatogenic diabetes, pseudocysts, splenic vein thrombosis, duodenal or biliary obstruction, pseudoaneurysm, pancreatic duct stones

#### **1. Introduction**

Chronic pancreatitis (CP) is an inflammatory disease that causes irreversible anatomical changes and damage including infiltration of inflammatory cells, fibrotic processes and calcifications formation with destruction of the gland structure and thus affects normal nutrients digestion and absorption. The clinically early phase is characterized by pain and recurrent acute pancreatitis episodes and complications, and the late phase by exo- and/or endocrine insufficiency. In 2016, a

new definition of CP was proposed, according to which CP is a fibro-inflammatory syndrome, affecting people with genetic, environmental and/or other risk factors, resulting in a persistent pathological response as a result of parenchymal injury or stress. In addition, some of the following features of advanced CP may be present in each patient: pancreatic atrophy, fibrosis, pain syndrome, ductal stricture, calcifications, pancreatic exocrine/endocrine insufficiency and dysplasia. The frequency of CP per year in the European population is 5–10/100,000. Alcohol abuse is the most observed cause. Recurrent episodes of acute pancreatitis and heredity as a contributing factor may result into CP development [1–7].

Pain is the most frequent symptom in CP patients, leading to quality of life impairment. It pathogenesis is still poorly understood. Multimodal approach, including lifestyle changes, medical therapy, pancreatic endoscopic and surgical procedures, and other non-pharmacological options are recommended [8, 9].

The pancreatic enzymes lipase, amylase, trypsin and chymotrypsin, released predominantly by the duodenal mucosa exposure of nutrients—especially lipids, are at a great importance for the macronutrient digestion. Their secretion comprises the following three phases—maximum, stable and basic secretion. Pancreatic enzymes amount and action duration depend on the caloric content maldigestion, the food type and its physical properties [1, 6, 7, 10, 11].

Pancreatic exocrine insufficiency (PEI) due to a progressive loss of acinar cells is a functional limitation of pancreatic enzyme and bicarbonate secretion, regardless its etiology, leading to digestive process deficiency. Main pathological mechanisms in adults are (1) Insufficient pancreatic secretory capacity, (2) Decreased gland stimulation, (3) Impaired enzymes release in the duodenum. The causes are divided into primary (chronic pancreatitis, cystic fibrosis, pancreatic agenesia, congenital pancreatic hypoplasia, Shwachman-Diamond syndrome, Johanson-Blizzard syndrome, pancreatic lipomatosis or atrophy, isolated lipase or co-lipase deficiency, pancreatic carcinoma, pancreatic resection) and secondary (reduced cholecystokinin releasing, somatostatinoma or exogenous administration of somatostatin, gastrinoma, (sub) total gastrectomy, resections and Billroth II anastomosis, periampullary tumors) [11–15].

Although not studied in-depth, the reported prevalence of PEI in patients with CP varies widely between 40 and 94%. The onset of PEI depends on the CP etiology and is about 10–15 years (5–6 years for alcoholic CP) after initiating the pathological CP processes, which is explained by the large functional reserve capacity. Decompensation occurs when the enzyme secretion is reduced by 90–95%. However, in some patients PEI symptoms such as malnutrition and/or abdominal symptoms (diarrhea, flatulence, pain), steatorrhea, body weight loss are first appearance of the disease [1, 7, 16–18].

Although steatorrhea is a typical symptom of a severe PEI, no clinical symptom unambiguously proves or excludes PEI. Steatorrhea may be absent or caused by pancreatic duct obstruction, low duodenal pH, decreased contact time due to increased motility, small intestinal bacterial overgrowth. Fat-soluble vitamin insufficiency, protein malnutrition, increased risk of osteoporosis and fractures, life-threatening complications such as cardiovascular events are further PEI complications [2, 5, 19–22].

An up-to-date assessment of pancreatic exocrine function allows diagnosis of PEI, initiation of pancreatic enzyme replacement therapy (PERT) and its monitoring. Pancreatic exocrine secretion can be assessed by direct and indirect methods. Direct tests are based on determination of volume, bicarbonates and/ or enzymes in the stimulated pancreatic gland by intravenous administration of hormones or their peptide analogs. These methods are invasive because duodenal

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*Up-To-Date View on the Clinical Manifestations and Complications of Chronic Pancreatitis*

intubation and a duodenal juice sample are required. Most indirect methods, which evaluate either the digestive ability of the pancreas or the pancreatic secretion by quantification of pancreatic enzymes, are non-invasive, but some require blood sampling and are then considered invasive. The clinical benefit of each method is based on diagnostic accuracy, relevance in clinical practice and cost

Pancreatic enzyme replacement therapy is an essential part of PEI treatment. Nowadays a majority of patients with PEI might be asymptomatic, receiving none or suboptimal PERT. They are at increased risk of PEI complications and impaired quality of life. Patients' compliance should be ensured. Periodical monitoring of PERT by nutritional assessment and BMI is mandatory with a respect to primary

Pancreatogenic diabetes or type 3c diabetes mellitus develops secondary to pancreatic disease. Recently, DM type 3c is a more recognizable entity due to new proposed criteria. It is a complex disease, further complicated by the presence of comorbidities such as maldigestion and accompanying malnutrition. Metformin is a treatment of choice. Annually screening for type 3c DM by fasting glucose levels and HbA1c is of a great importance in patients with CP regardless the grade of

Many studies are conducted to demonstrate the association between CP with tropical and hereditary etiology and DM with pancreatic cancer development. The pathogenesis of malignant transformation on the basis of CP remains unclear. Biomarkers and imaging modalities are used to distinguish inflammation form

The management of the miscellaneous CP complications pseudocysts, splenic vein thrombosis, duodenal and biliary obstruction, pseudoaneurysm, pancreatic calculi

**2. Clinical manifestations of chronic pancreatitis and their management**

Abdominal pain is a predominant symptom, affecting 80–90% of patients with CP. Pain significantly reduce quality of life. Pathogenesis is still poorly understood. Multifactorial mechanisms are proposed, including inflammation; duct obstruction followed by hypertension and ischemia; neuronal damage—neuropathic and dysfunctional pain due to hypersensitivity, central and spinal nociceptive neurons alterations. Alcohol and tobacco have contributing role for pain exacerbation. Pancreatic pain covers the characteristics of visceral pain—diffuse severe dull persistent pain, usually with epigastrium location and further radiation to the back, left or right hypochondria. Pain is not necessarily linked to a new acute episode and often worsens with food intake. Pain could be recurrent, during acute episodes and prolonged. Questionnaire scales could be used for pain characterization: Izbicki pain score, brief pain inventory (validated for CP), quantitative sensory testing. According to newest guidelines a multi-modal approach, including lifestyle changes, medical therapy and non-pharmacological approaches, is recommended. Alcohol and tobacco cessation should be advised in all patients. PERT could release pain in patients with ductal obstruction as oral enzymes reduce cholecystokinin levels and therefore decrease pancreatic juice secretion, leading otherwise to duct hypertension. A combination of antioxidants is useful to reduce the oxidative stress and damage. According to the published in 1986 WHO stepwise analgesic's approach is recommended. Simple

and secondary prophylaxis of risk factors [1, 6, 18, 26–30].

pathological structural changes [17, 18, 20, 31, 32].

consists of their screening and treating [23].

*DOI: http://dx.doi.org/10.5772/intechopen.84738*

[20, 23–25].

neoplasia [33, 34].

**2.1 Abdominal pain**

#### *Up-To-Date View on the Clinical Manifestations and Complications of Chronic Pancreatitis DOI: http://dx.doi.org/10.5772/intechopen.84738*

intubation and a duodenal juice sample are required. Most indirect methods, which evaluate either the digestive ability of the pancreas or the pancreatic secretion by quantification of pancreatic enzymes, are non-invasive, but some require blood sampling and are then considered invasive. The clinical benefit of each method is based on diagnostic accuracy, relevance in clinical practice and cost [20, 23–25].

Pancreatic enzyme replacement therapy is an essential part of PEI treatment. Nowadays a majority of patients with PEI might be asymptomatic, receiving none or suboptimal PERT. They are at increased risk of PEI complications and impaired quality of life. Patients' compliance should be ensured. Periodical monitoring of PERT by nutritional assessment and BMI is mandatory with a respect to primary and secondary prophylaxis of risk factors [1, 6, 18, 26–30].

Pancreatogenic diabetes or type 3c diabetes mellitus develops secondary to pancreatic disease. Recently, DM type 3c is a more recognizable entity due to new proposed criteria. It is a complex disease, further complicated by the presence of comorbidities such as maldigestion and accompanying malnutrition. Metformin is a treatment of choice. Annually screening for type 3c DM by fasting glucose levels and HbA1c is of a great importance in patients with CP regardless the grade of pathological structural changes [17, 18, 20, 31, 32].

Many studies are conducted to demonstrate the association between CP with tropical and hereditary etiology and DM with pancreatic cancer development. The pathogenesis of malignant transformation on the basis of CP remains unclear. Biomarkers and imaging modalities are used to distinguish inflammation form neoplasia [33, 34].

The management of the miscellaneous CP complications pseudocysts, splenic vein thrombosis, duodenal and biliary obstruction, pseudoaneurysm, pancreatic calculi consists of their screening and treating [23].
