**Abstract**

Pancreatic insufficiency, both acute and chronic, is an important cause of maldigestion and malnutrition caused by impaired exocrine pancreatic function. Many causes are able to determine pancreatic insufficiency which, depending on the severity, can manifest itself with very diversified symptoms. The chapter will illustrate the diagnostic and monitoring methods of pancreatic pathology in the acute and chronic phases. Great attention will be given to oral nutrition, in its various forms, including enteral and peranterior artificial nutrition. Finally, we will discuss the most appropriate pharmacological therapy to optimise food absorption in the different phases of the disease. Each of the aspects considered takes into account the most recent literature and the clinical experience of the authors.

**Keywords:** acute pancreatitis, chronic pancreatitis, artificial nutrition, pancreatic insufficiency, pancreas diet

## **1. Introduction**

### **1.1 Symptoms and causes of acute pancreatitis**

Pancreatitis is an inflammatory process, either acute or chronic, resulting from the outset, caused by digestive enzymes, of a process of self-digestion of the pancreas, and resulting in a complex inflammatory pattern which is extremely challenging for patients. Since even organs and systems located far from the pancreas can be variably involved in such pattern, the manifestations and the intensity of the disease may prove extremely severe, to the point of endangering the patient's life [1, 2].

A healthy pancreas synthesises over 10 digestive enzymes in the acinal cells, while the pancreatic ducts host the production of bicarbonate, whose function is that of neutralising the acid content of the stomach when it reaches the duodenum. The increased pH makes the duodenum the ideal environment for the pancreatic and the jejunal digestive brush border enzymes. Complex factors contribute to the stimulation of the exocrine pancreas, including the intake of highly caloric food (>500 kcal), the presence of free fatty acids in the duodenum, the intake of essential aminoacids (phenylalanine, valine, methionine, tryptophane) and solid rather than liquid or

semi-liquid dietary consumption (slower gastric emptying). The exocrine stimulation mainly occurs through the vagus nerve and the secretion of cholecystokinin (CCK) [3–5].

The onset of Acute Pancreatitis may be sudden, with pain ranging from mild to severe and often accompanied by fever, nausea and vomiting. The intensity of the pain, typically located in the epigastric area, is not always correlated with the disease severity and may radiate towards the back, the chest or the hips (**Tables 1** and **2**) [6, 7].

Data regarding the severity of the clinical picture and that of any complications are essential in the prognosis. Scores have been elaborated aimed at quantifying the severity of the clinical picture (Ranson's score; Harmless Acute Pancreatitis Score [HAPS]; Modified Glasgow Acute Pancreatitis Severity Score; Atlanta Score for Acute Pancreatitis 2013; Bedside Index for Severity in Acute Pancreatitis) [8–12]. These scores are frequently associated with systemic assessment scores such as the Marshall Score (**Table 3**) [13]. Predictive symptoms of clinical worsening in patients with Acute Pancreatitis are: body temperature < 36 o > 38°C (<96 or > 100°F), heart rate > 90/min, respiratory rate > 20/min, white blood cells <4 x 109/L or > 12 x 109 L (<4 or > 12 K/mm3).


artery occlusion).

**Table 1.**

*Symptoms and signs of acute pancreatitis.*


### **Table 2.**

*Frequency of signs and symptoms in acute pancreatitis.*


*Note: score* ≥ *2 over a period of more than 48 hours, for any one of the three organ systems: persistent organ failure; score* ≥ *2 over a period of less than 48 hours: transient organ failure.*

### **Table 3.**

*Modified Marshall system to evaluate organ failure.*

The main aetiopathological mechanisms involved in Acute Pancreatitis are summarised in **Figure 1** [14]. Their main cause is the obstruction, due to the presence of gallstones, of the biliary tract or pancreatic duct (40–70% of cases). The second

**Figure 1.** *Main mechanisms involved in acute pancreatitis.*


### **Table 4.**

*Main causes of acute pancreatitis.*

most frequent cause is alcohol consumption (25–35% of cases). Other less common causes are hyper-triglyceridemia (>1.000 mg/dL) and the presence of benign or malign Pancreatic tumours (**Table 4**). The immune system appears to play an important role in the progression of Acute Pancreatitis, since the release of proinflammatory mediators during the self-digestion phase might result in Necrotizing Pancreatitis. In this context, the small intestine barrier may become permeable to the transit of bacteria (bacterial translocation) from the enteric lumen to the lymphatic and blood systems, allowing Multiple Organ Dysfunction Syndrome to occur (**Figure 2**) [15, 16].

### **1.2 General aspects of pancreatitis treatment**

Acute Pancreatitis can be classified according to clinical severity (**Table 5**) [2]. While in cases of Mild or Moderate Acute Pancreatitis organ failure and/or pancreatic necrosis hardly occur, in Medium-Severe cases there may be pancreas tissue necrosis without persistent organ failure; in severe cases, the disease progression can have an initial phase with local inflammation of the pancreas associated with a systemic inflammatory response related to the syndrome/organ failure, and a later phase with local complications and/or persistent organ damage. It is estimated that about 15–20% of the patients present a Severe Pancreatitis profile with organ failure (>8 hours). Another 20% present a Necrotizing Pancreatitis profile defined as focal areas of nonviable pancreatic parenchyma (>3 cm in size or > 30% of the pancreas) [18].

Being this distinction among Mild, Medium and Severe Pancreatitis obviously reductive and not always immediate, Acute Pancreatitis is diagnosed, in presence of abdominal pain in patients with a medical history and/or familiarity for the disease, by monitoring pancreatic health (serum amylase or lipase at least three times higher than the highest value within the normal range). Abdominal Imaging (CT or MRI) is generally crucial for the diagnosis (**Table 6**) [19, 20].

The treatment is aimed at reducing the systemic inflammatory response so as to prevent, where possible, organ failure and systemic complications. There being no

**Figure 2.** *Multi-organic mechanisms involved in acute pancreatitis.*


### **Table 5.**

*Grading severity of acute pancreatitis according to Atlanta criteria 2012 [17].*


### **Table 6.**

*Diagnostic aspects in patients with pancreatitis.*

specific pharmacological treatment to this date, hydro-electrolyte re-balancing, use of analgesics, antibiotics and management of metabolic complications (hyperglycemia and hypocalcemia) are at the core of today's treatment.

Overall, Mild Acute Pancreatitis should be treated with fluids, analgesics and antibiotics for a few days only in presence of infectious complications (never for prophylactic purposes), whereas Severe Acute Pancreatitis requires an accurate inspection, since patients must undergo surgical removal of gallstones, re-activation of the bilious-pancreatic ducts and, in rare cases, elimination of the necrotic tissue through partial or total removal of the the pancreas and/or attached organs [21].

### **1.3 Evaluation of the nutritional status**

Maximum catabolism with negative nitrogen balance is not uncommon, especially in the most severe cases of Acute Pancreatitis [22, 23]. The resulting high increase in calorie (Resting Energy Expenditure) and protein need might rapidly lead, if not promptly managed, to malnutrition (**Figure 3**) [24]. Malnutrition, being associated with severe weight loss, lean body mass loss and decreased functional capacity due to sarcopenia, is likely to affect quality of life and clinical outcomes [25]. Possibly asthenia and/or loss of appetite, leading to reduced calorie-protein intake, contribute to weight loss, hence to malabsorption and maldigestion. In case of sudden weight loss (10% of habitual weight in about 3–6 months), malnutrition might pair with the main disease, leading to acute or chronic complications which may worsen the patient's prognosis (**Table 7**).

Therefore, the aetiology of malnutrition is heterogeneous and may depend on the severity of the disease, the patient's ability to eat food and the catabolic state. Old age and immobilisation may contribute to raise the risk of malnutrition (**Figure 4**) [26]. Full-blown malnutrition becomes a disease which adds up to the underlying disease. Patients with Acute Pancreatitis should be considered at high risk of malnutrition.

To confirm this, literature shows that about 30% of patients with Acute Pancreatitis are malnourished and that they do not receive adequate nutritional support, which makes accurate Nutritional Screenings such as the Nutritional Risk Screening 2002 (NRS-2002) necessary in order to objectively evaluate the risk of hypo/malnutrition. **Table 8** shows some of the most employed Screening Tools.

**Figure 3.** *Relationship between energy intake and expenditure (see text).*
