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Molecular, Biochemical, andMetabolic Abnormalities ofAcute Pancreatitis

Downloaded from https://onlinelibrary.wiley.com/doi/ by Universität Bern, Wiley Online Library on [22/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

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only transient clinical outcome was good (mortality below 1%), whereas persistent organ failure resulted in a mortality rate of 35%[1]. A better understanding of the pathogenesis of early multiorgan failure might therefore be essential for the development of new strategies for the prevention or treatment acute pancreatitis.

Pathogenesis ofPulmonary Failure

ARDS (acute respiratory distress syndrome), later termed ALI (acute lung injury) is a frequently occurring manifestation of organ dysfunction in an intensive care setting and can be the cause of death in critically ill patients. The exact incidence remains unknown but may be as high as 75 per 100,000 population in the USA[23]. Overall acute pancreatitis is a condition in which patients rarely develop ARDS (8%) of total, but severe attacks are frequently associated with acute lung injury (ALI) and respiratory failure (ARDS). The definition set in 1994 for ALI reads as follows: a syndrome of inflammation and increased permeability that is associated with a constellation of clinical, radiological, physiologic abnormalities that cannot be explained by, but may coexist with, left atrial or pulmonary capillary hypertension[24]. The distinction between ALI and ARDS is the degree of hypoxemia. The incidence of pulmonary complications in acute pancreatitis varies between 15% and 55% and their severity ranges from mild hypoxemia without clinical or radiological signs to severe ARDS. The major cause of hypoxemia is ventilation/perfusion mismatch, which results in right to left pulmonary shunting. In ARDS the injured lung is believed to go through three phases: exudative, proliferative, and fibrotic but the course of each phase and the overall disease progression are variable. The pathophysiological features of the lung in ARDS arise from severe injury to the alveolo- capillary unit. The histological features are dense eosinophilic hyaline membranes and alveolar collapse. The endothelial cells swell, the intercellular junctions widen and pinocytic vesicles increase, causing capillary leak and edema formation. Approximately 10% of patients with acute pancreatitis show alveolar edema on chest radiographs and one third of patients develop progressive hypoxemia during the first week of hospitalization[45]. The cause for the development of alveolar edema is an increase in microvascular permeability in the context of SIRS. This was shown by applying labelled transferrin as an indicator for lung vascular permeability within 48 hours after hospital admission, which was found to be significantly increased in the lung tissue of patients who had later died in the disease process [25]. A similar observation demonstrated an increase in the gallium- transferrin pulmonary leak index strongly correlated with the mortality rate[26].

Lankisch and coworkers determined the incidence of pulmonary infiltrates in 140 consecutive patients with acute pancreatitis with 26% within 24 hours after admission to hospital[27] (see Fig.16.1). The mortality rate of acute pancreatitis significantly correlated with the presence of pulmonary infiltrates and effusions. Logistic regression analysis showed that radiologic abnormalities were associated with a 15- fold increase in mortality rate. A reduced PaO2 on hospital admission has long been regarded as a prognostic factor for the severity of pancreatitis and is part of the Ranson Score, the Imrie Score, and the newly released UK guidelines, which recommend to hold peripheral oxygen saturation above 95% to prevent organ failure as a treatment goal[28].

With respect to the pathophysiology of ARDS in acute pancreatitis two case series showed that massive cytokine release may have a contributing role in SIRS. Especially IL- 8was reported to be significantly higher in patients at admission who later developed acute severe lung injury [29]. In pleural effusions TNF- α, IL- 1, IL- 6, and PMN- elastase were significantly higher in serum in ARDS patients, which may point to a direct impact of these cytokines on the development of ARDS but could also occur because of a diminished excretion of cytokines into pleural effusions[30].

Phospholipase A2 (PLA- 2) has long been regarded as a major culprit for acute lung injury in acute pancreatitis. Out of numerous phospholipase A2 (PLA- 2) subtypes, PLA- 2 type I and PLA- 2 type II, have been implicated in the pathogenesis of pancreatitis. PLA- 2 type I is expressed by pancreatic acini (cytoplasmic PLA- 2 type Ib). Data from Creutzfeldt and coworkers dating back to

Figure16.1 Severe adult respiratory distress syndrome in severe

acute pancreatitis.

Metabolic andSystemic Abnormalities 159

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1969 suggested that PLA- 2 type II is responsible for the cell necrosis in acute pancreatitis by converting its endogenous substrate lecithin (part of the lipid bilayer of cell membranes) into the more toxic compound lysolecithin. Thus PLA- 2 could break down pulmonary surfactant which consists of phospholipids and could therefore impair oxygenation and increase vascular permeability. This notion was confirmed as elevated circulating plasma levels of PLA- 2 correlated with more severe pulmonary changes in patients with gramnegative septic shock [31]. Furthermore, intratracheal application of nonpancreatic PLA- 2induced lung injury with interstitial edema and accumulation of inflammatory cells, but the concept that release of pancreatic PLA- 2 from necrotic acinar cells mediates lung injury had to be abandoned. In addition to the hypothesis of a direct impact of PLA-

2 other pancreatic zymogens and nitric oxide released from pulmonary macrophages have been implicated in contributing to pulmonary complications in acute pancreatitis. An experimental study testing this concept showed that intravenous application of elastase or trypsin resulted not only in pulmonary damage through NFκB activation and TNF- α release with subsequent transmigration of neutrophils but also in an increase in lung vascular permeability. Neutrophils have been implicated in mediating lung injury in acute pancreatitis and inhibition of neutrophil- derived serine proteases such as PMN- elastase seem to be promising treatment targets[32].

In conclusion, severe attacks of acute pancreatitis are frequently associated with acute lung injury. Arterial hypoxemia, pulmonary infiltrates, pleural effusions as well as ARDS may develop as complications of the disease. Within the first few days following the onset of severe acute pancreatitis lung injury develops because ofacute pancreatitis. Sepsis is the predominant cause of lung injury in the later phase of the disease. Besides best supportive care, protective mechanical ventilation, hemodynamic monitoring as well as enteral nutrition and renal replacement therapy have been considered to be of potential benefit to treat pulmonary complications.

Pathogenesis ofRenal Failure

Acute renal failure (ARF) occurs in 19% of patients with moderate sepsis, 23% with severe sepsis, and 51% with septic shock with positive blood cultures [33]. The cytokine- mediated induction of nitric oxide synthesis that occurs in SIRS and sepsis decreases systemic vascular resistance. This arterial vasodilatation predisposes patients with SIRS to ARF [34]. Patients who develop ARF in the setting of critical illness are more likely to die than dialysis- dependent patients admitted to ICU, suggesting that the bad outcome associated with the recent

development of renal failure is due to SIRS, rather than merely due to renal dysfunction [35]. The clinical syndrome of ARF in the setting of critical illness, manifested by rising serum creatinine and decreasing urine output, results from injury to the tubular epithelial cells or acute tubular necrosis. In necrotizing pancreatitis renal insufficiency occurs in 21% of patients after a median time period of 8.3days after the onset of pancreatitis. In analogy to the pathogenesis of ARF in critically ill patients suffering from SIRS a combined pathomechanism of prerenal failure due to extensive fluid loss into the third space together with a prolonged cytokine-

mediated organ failure even after fluid resuscitation can be assumed to be operative. Simmons and coworkers showed that increased plasma proinflammatory cytokine levels (TNF- α, IL- 1b, IL- 6) predict the mortality in patients with ARF[36]. This finding is supported by the fact that in animal models infusion of high concentrations of proinflammatory cytokines can lead directly to the development of multiorgan system failure. Furthermore, patients with SIRS and associated ARF show signs of intense endothelial damage and hypercoagulability as indicated by increased vWF, thrombomodulin, t-

PA, PAI- 1, and D- dimer activity[37]. In conclusion, ARF is a frequent extrapancreatic complication of acute pancreatitis but studies on the pathogenesis of ARF are urgently needed to treat this potentially fatal complication.

Pathogenesis ofParalytic Ileus andGut Permeability

Patients with acute pancreatitis often suffer from severe intestinal motility disturbances, which render them prone to bacterial translocation into the pancreatic necrosis due to bacterial overgrowth and increased gut permeability, which is then burdened with an increase in mortality (Fig. 16.2). Studies on CDE- diet fed mice revealed that acute necrotizing pancreatitis inhibits gastric emptying and intestinal transit invivo. The global reduction in jejunal contractility is explained by the disruption of the intestinal motor function at the postreceptor level, which plays an important role for the development of an intestinal ileus during acute pancreatitis[38].

In an animal model of acute pancreatitis Ryan and coworkers reported a significant increase in intestinal permeability to macromolecules that correlated with disease severity. The pathogenesis of gut barrier failure can be attributed to local (intestinal) factors namely: mucosal ischemia, disruption of mucosal epithelial integrity, reperfusion injury, disruption of intestinal bacterial ecology, as well as impaired mucosal immunity. Thoracic epidural analgesia for pain also augments ileal mucosal capillary perfusion and improves survival in severe acute pancreatitis[39].

Molecular, Biochemical, andMetabolic Abnormalities ofAcute Pancreatitis

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mechanism is incompletely understood, recombinant APC decreased the levels of IL- 6 and D- dimer and reduced mortality in severe sepsis patients. Investigating levels of APC, PC, and D- dimer in 31 patients with severe acute pancreatitis showed that PC deficiency and decreased APC generation contributed to a compromised anticoagulant- and anti- inflammatory defence, which subsequently aggravated multiorgan failure. Clinical trials evaluating treatment with PC are warranted in severe acute pancreatitis. In addition to the therapeutic impact of restoring coagulation in severe acute pancreatitis a recent clinical study has shown that signs of disseminated intravascular coagulation are also of high prognostic value. The aggravated coagulation parameters predict a fatal outcome in patients with acute pancreatitis. An AT- III level <69% was the most accurate marker for poor outcome of acute pancreatitis at admission[43].

Figure16.2 Paralytic ileus in severe acute pancreatitis.

Pathogenesis ofCoagulopathies

The systemic inflammatory reaction and the development of organ failure in acute pancreatitis share similarities with a complicated course of sepsis, major trauma, or burns [40]. Ranson and coworkers noted abnormalities in coagulation factors during severe acute pancreatitis. They concluded from a prospective analysis of 35 patients in which they correlated amylase levels with respiratory, renal, and hepatic dysfunction that enzyme- related intravascular coagulation is involved in the pathogenesis of these coagulation complications during acute pancreatitis[41]. In systemic inflammation a rapid activation of coagulation may turn into a global or selective exhaustion of

physiological anticoagulant systems. The interactions between coagulation and inflammatory pathways are essential for the pathogenesis of disseminated intravascular coagulation. For example, the proinflammatory cytokines TNF- α, IL- 1, and IL- 6 upregulate thrombin formation and downregulate physiological antithrombotic defence mechanisms, especially the protein C pathway [42]. The protein C pathway is both a major physiological anticoagulant system and a central link between inflammation and coagulation. The zymogen protein C is converted to activated protein C (APC) by thrombin bound to thrombomodulin on the endothelial surface. While the underlying

Electrocardiographic Abnormalities inAcute Pancreatitis

Acute pancreatitis has been reported to be associated with electrocardiographic abnormalities including arrhythmias, bradycardia, T- wave changes, intraventricular conduction disturbances, and ST- segment elevation termed “pseudoinfarction” (Fig.16.3). The clinical relevance and causes of such electric abnormalities are poorly understood. However, experimental studies performed on a murine model of acute pancreatitis have reported ultrastructural disturbances including interstitial edema and cardiomyocyte hypoxia, myofiber overcontractility, intracellular edema between cardiomyocytes, and cardiomyocyte hypertrophy with collagenization of myocardial stroma[44]. Albrecht and Laws proposed a direct cardiotoxic effect of proteolytic pancreatic enzymes as a cause of ST- segment elevation and myocardium specific enzyme increase (particularly phosphokinase MB fraction). Other mechanisms that have been proposed to explain electrocardiographic abnormalities appearing during AP are those associated to metabolic disturbances, hemodynamic instability, vasopressor drug use, pericarditis, myocarditis, exacerbation of underlying cardiac disease, coagulopathy, and coronary artery spasm[45]. Patients with acute pancreatitis have a high risk to develop metabolic abnormalities. The consequences of low or high serum electrolyte levels on cardiac electric activity include changes in the T- wave morphology, bundle branch blocks arrhythmias, QT- internal shortening or prolongation, asystole, prominent U- wave, ST- segment depression or elevation, ventricular fibrillation[46]. Recently two prospective studies have reported abnormalities on ECG and correlated these changes to the severity of acute pancreatitis.

Figure16.3 ECG changes in severe hypo volemia

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and hypopotassemia.

The Role ofHypocalcemia and Hypomagnesemia 161

ECG

Blood Pressure

The Role ofHypocalcemia and Hypomagnesemia

Hypocalcemia is a frequent finding in patients with severe acute pancreatitis and has been implicated to be of prognostic value by the Ranson scoring system[47]. It has been demonstrated that hypocalcemia is more frequent in severe attacks as compared to mild attacks of pancreatitis (86% vs. 39%)[48]. Prevalence of hypocalcemia ranges between 15% and 88% in critically ill patients. Several pathogenetic mechanisms contribute to the development of hypocalcemia and need to be considered in evaluating hypocalcemia: (i) Serum calcium levels reflect only part of the physiologically active ionized calcium. More than half of the circulating calcium is bound to albumin and serum calcium levels need to be corrected for serum albumin levels as albumin is lost to the third space. When calcium levels are corrected for albumin, the majority of patients display normocalcemia, which explains the absent symptoms of hypocalcemia like arrhythmias and tetany. (ii) In response to decreased serum calcium levels circulating parathyroid hormone levels (PTH) are increased. This subsequently leads to calcium mobilization from bone and calcium reabsorption in the kidneys is increased. In a prospective study by McKay PTH levels were determined to be invariably elevated in response to hypocalcemia in acute pancreatitis but significantly increased concentrations were found in patients with a complicated course of the disease [49]. Inadequate mobilization of calcium from bone indicating endcould offer an alternative explanation for hypocalcemia. However, patients suffering from acute pancreatitis

organ failure

were shown to react with an adequate rise in serum calcium levels and urinary cyclic adenosine monophosphate upon infusion of exogenous PTH. These findings had been previously substantiated by data from animal experiments [25]. Hypomagnesemia together with hypocalcemia can inhibit PTH secretion as well as peripheral action of PTH. Intracellular magnesium levels in patients with acute pancreatitis are thus believed to be decreased [50]. Patients with acute pancreatitis and hypocalcemia commonly also show intracellular magnesium deficiency despite normal serum magnesium concentrations. Magnesium deficiency could therefore play a significant role in the pathogenesis of hypocalcemia in acute pancreatitis. It has been reported that bivalent cation Mg2+ counteracts the intracellular calcium signaling and thereby ameliorates the deleterious effect of intracellular premature zymogen activation. Moreover, in preliminary experiments we were able to show that Mg

- therapy readily administered as a food supplement in an animal model of acute pancreatitis has a beneficial effect on the course of the disease. Currently we are conducting a multicenter, multinational, randomized, placebo- controlled phase II trial to investigate the efficacy of oral magnesium for the prevention of painful acute episodes of hereditary and idiopathic pancreatitis (EUROPAC- 2) [3]. The role of increased free fatty acids (FAA) in the pathogenesis of hypocalcemia in acute pancreatitis has not been clearly elucidated and different pathophysiological mechanisms have been proposed. Circulating lipase and phospholipase released from necrotic pancreatic acinar cells may cleave triglycerides and hereby lead to elevated serum FAA. Warshaw determined the effect of FFA on

Molecular, Biochemical, andMetabolic Abnormalities ofAcute Pancreatitis

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serum calcium levels in an animal model. His findings suggested that (i) changes in the concentration of FFA occur spontaneously but may have an impact on calcium levels; (ii) the observed depression of calcium may be due to intravascular sequestration of calcium by FFAalbumin, but increased flux of circulating calcium- FFA

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Histopathology ofAcute Pancreatitis

Günter Klöppel

Department of Pathology, Consultation Center for Pancreatic and Endocrine Tumors, Technical University Munich, Munich, Germany

Introduction

In this chapter, the histopathology of acute pancreatitis is reviewed and the various patterns of tissue damage that have been described so far are related to the known etiologic factors and the discussed pathogenetic mechanisms. Finally, an attempt is made to correlate the histopathologic findings with the clinical and radiologic criteria of the 2012 Atlanta Classification of Acute Pancreatitis [1] that revised the 1992 Atlanta classification[2].

Definition

Acute pancreatitis is in most cases a necroinflammatory autodigestive damage that initially involves the intrapancreatic and extrapancreatic fatty tissue and is caused by noninfectious factors. Rarely acute pancreatitis has an infectious cause and shows initially an acinar cell necrosis [3]. Clinically and histologically, it can be classified into a mild form called acute interstitial edematous pancreatitis affecting 90–95% of patients, and a severe form called acute necrotizing pancreatitis affecting only 5–10% of patients. The mild form of acute pancreatitis is often associated with gallstone disease, while the severe form is usually linked to alcoholism.

Histopathologic Patterns ofTissue Necrosis

Fatty tissue necrosis within and outside the pancreas is the most frequent histologic lesion that can be seen during the initial phase of most cases of acute pancreatitis based on an

autodigestive process (type 1necrosis pattern) (Fig.17.1). The necrotic process that emanates from fat cells in the interlobular spaces of the pancreas and in the peripancreatic area, and the later inflammatory reaction, are very variable in degree and extent. Another, but rare, pattern of tissue damage is characterized by necrosis of the duct epithelium which becomes the starting point of a ductal and periductal inflammation. In the third pattern, which is also rare, the acinar cell necrosis is the key lesion that is followed by a perifocal intralobular inflammation[4].

Acute Pancreatitis withFatty Tissue Necrosis Pattern

Most cases of mild and severe acute pancreatitis are characterized by the fatty tissue necrosis pattern. The degree and extent of this necrosis pattern determines the severity and the course of acute pancreatitis and its classification into mild/interstitial edematous or severe/ necrotizing pancreatitis[1] (Table17.1).

Initial Phase

Interstitial pancreatitis leads commonly to an edematous swelling of the pancreas, but the pancreas may also be normal in size. In addition the pancreas displays tiny white disseminated spots of fatty tissue necrosis on its surface and also in the interlobular fatty tissue [5] (Fig. 17.2). Because this form of pancreatitis has a mild nonlethal course, the study of the described histologic changes is nowadays largely limited to rare resected pancreatic tissue specimens, in which an interstitial pancreatitis developed, either in association with long- term operations or in conjunction with preoperative investigations.

The Pancreas: An Integrated Textbook of Basic Science, Medicine, and Surgery, Fourth Edition. Edited by Hans G. Beger, Markus W. Büchler, RalphH. Hruban, Julia Mayerle, John P. Neoptolemos, Tooru Shimosegawa, Andrew L. Warshaw, David C. Whitcomb, and Yupei Zhao. © 2023 John Wiley & Sons Ltd. Published 2023 by John Wiley & Sons Ltd. Companion website: www.wiley.com/go/beger/thepancreas4e

Lobule

Enzymes

Causes

Acute pancreatitis

Normal pancreas

Necrosi pattern

and activation

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Acute Pancreatitis withFatty Tissue Necrosis Pattern 165

Duct

Alcohol gallstones

Type 1 Type 2 Type 3

Enzymes

Lesion Ductal and

Figure17.1 Schematic presentation of three necrosis patterns observed in human acute pancreatitis related to potential causative factors.

Table17.1 Atlanta classification 2012 ofacute pancreatitis: type andseverity correlated withcomplications, imaging findings

andhistopathologic features.

Type and severity Complications and imaging findings Histopathologic features

Interstitial edematous pancreatitis

Mild 

Moderately severe

Necrotizing pancreatitis

Severe

Autodigestive fat necrosis

due to enzyme effusion

Prolonged circulatory failure

Enzymes

periductal necrosis



None 

Transient organ failure and/or acute peripancreatic fluid collection (APFC)

Pseudocyst (deriving from unresolved APFC)



Acute necrotic collection (ANC) with persistent organ failure and systemic complications

off necrosis (deriving from ANC)

Walled-

Auto

Activation

Infectious disease

Disseminated acinar necrosis

Enzymes



Parenchymal edema with tiny fat necroses Peripancreatic fat necrosis

 

Pseudocyst (without debris)



Large peripancreatic fat necrosis with or without parenchymal necrosis and hemorrhage 

Well- demarcated pseudocyst emerged from peripancreatic and pancreatic necrosis

Necrotizing pancreatitis is characterized by numerous large and confluent areas of fat necroses extending into the peripancreatic tissue (Fig.17.3). In addition, the pancreas shows parenchymal necrosis, although it is usually much less extensive than the peripancreatic necrosis. The extent of fat necrosis correlates roughly with the amount of interlobular fatty tissue present in the individual pancreas. This means that the pancreas of obese subjects may show more extensive necrosis than the pancreas of normal weight individuals. Where large fat necrosis involves blood vessels, especially veins, the necrosis becomes hemorrhagic, because of vessel wall damage followed by thrombosis or

rupture. Arteries, because of their thick walls, are more resistant to necrosis, but if also affected, can develop thrombosis, resulting in panlobular ischemic necrosis. Another important complication of large fat necrosis that involves the surrounding tissues, is the destruction and thus opening of interlobular ducts that lead to duct leakage of secretions. Surprisingly, acinar cells adjacent to fat necrosis seem to be well preserved for a long time. The only change may be a widening of acinar lumina, which have PAS- positive secretions. The islets are not affected, unless they are lying in lobules that are largely or entirely necrotic. In the course of the disease, the necrotic foci are

Histopathology ofAcute Pancreatitis

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166

Figure17.2 Acute interstitial pancreatitis: tiny fatty tissue necrosis

within the pancreas. Note the preservation of the adjacent acinar cells.

Figure17.3 Acute necrotizing pancreatitis: extensive peripancreatic

fat necrosis with hemorrhage involving the wall of a duct (top) and extending into the interlobular spaces of the pancreatic tissue below.

delimited by a collar of foamy macrophages intermingled with granulocytes that later are increasingly replaced by myofibroblasts to build up a wall of granulation tissue separating the necrosis from intact tissue.

Outcome

fluid collection,” are rare. If such a rare lesion does not resolve and gets encapsulated by granulation tissue (see later), it may become a pseudocyst.

In necrotizing pancreatitis, the large fat necroses liq-

uefy. Follow-

up studies by imaging have shown that necroses not exceeding 2–5 cm in diameter, can be slowly reabsorbed by macrophages. Larger necrotic areas (usually >5 cm), especially when they also involve pancreatic parenchyma, may not resolve spontaneously and their liquefied and hemorrhagic content is then lined by macrophages that, together with some granulocytes and lymphocytes, form a thin layer of granulation tissue within 10–20 days of the onset of the disease. This change may correspond with an “acute necrotic collection” as described by the radiologist (Table 17.1) [6]. Often the macrophages in the granulation tissue contain hemosiderin as a sign of the phagocytosis of hemorrhagic tissue. After 20–30 days, the granulation tissue starts to be replaced by fibrosis with collagen type 1 and

3. If the fibrotic demarcation is fully developed the change is radiologically called “walled-

off necrosis” that corresponds to the old term “pseudocyst associated with necrosis” (Table17.1). Most of these advanced lesions are found outside the pancreas, particularly around the head of the pancreas [7,8]. The fact that walled- off necroses/pseudocysts contain amylase suggests communications with the pancreatic duct system. This may be particularly the case in those pseudocysts which, in time, increase in size and by growing compress or erode such structures as the bile duct, duodenum, stomach, vessels, or peritoneum. The involvement of vessels may also lead to sudden hemorrhage.

Another severe complication is a colonization of the necrotic areas with (mostly gut- derived) bacteria or fungi. This usually takes place during the period (days 4–20) when the demarcation of the liquefied necrotic area still consists of only a small rim of granulation tissue.

The resolution of necrotic tissue within the interstitial spaces of the pancreas is usually followed by the development of interlobular fibrosis replacing the necrotic tissue (Fig.17.4)[9,10]. If this necrosis-

fibrosis process[11] takes place repeatedly because of recurrent attacks of necrotizing acute pancreatitis, and also involves the large interlobular ducts and the main duct, relapsing acute pancreatitis may evolve into chronic pancreatitis[12,13].

In interstitial pancreatitis, the edema, which is probably rich in pancreatic enzymes, is usually resolved by macrophages within a few days and leaves no changes behind. The same happens to the tiny foci of fat necrosis. Since the diameter of these fat necroses are usually smaller than 10 mm, they are barely detectable by imaging. Larger liquefied foci of peripancreatic fat necrosis, which probably correspond to the radiologic lesion called “acute peripancreatic

Acute Pancreatitis withDuct Epithelium Necrosis Pattern

Initial Phase

Disseminated duct cell necrosis of small to mediumsized interlobular ducts as initial key lesion is accompanied by intraductal aggregates of granulocytes mixed

Acute Pancreatitis withAcinar Type Necrosis Pattern 167

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that was usually not caused by acute pancreatitis, but by various extrapancreatic diseases such as hepatic failure. Our only observation of type 2necrosis so far, made in a pancreatic resection specimen from a patient with hereditary pancreatitis [16], could suggest that in this setting the initial necrosis of the ductlining cells, followed by an inflammatory involvement of the surrounding interstitial tissue, may result in structural changes such as irregular dilatations and periductal scarring of the affected pancreatic ducts.

Acute Pancreatitis withAcinar Type Necrosis Pattern

Figure17.4 Acute necrotizing pancreatitis 6weeks after onset.

Development of cellresorption of a fat necrosis (center). H&E, ×125.

Figure17.5 Acute pancreatitis with duct epithelium necrosis

pattern. Interlobular duct filled with aggregated neutrophilic granulocytes and secretions. Rupture of the duct epithelium with granulocytes infiltrating the periductal interstitial space. H&E, ×120.

rich interlobular fibrosis induced by the

with precipitations of eosinophilic secretions. There is also duct rupture and extension of the necrotic process and the granulocytic process into the periductal area (Fig. 17.5). This may be a solitary change, but is also observed in association with foci of fat necrosis elsewhere[14–16]. The ensuing acute pancreatitis seems to be usually mild.

Initial Phase

Scattered intralobular foci of acinar cell necrosis are the key lesions of this type of necrosis in acute pancreatitis (Fig.17.6). It is accompanied by a perifocal inflammatory infiltrate consisting of single neutrophil granulocytes and macrophages. Fat and ductal necrosis are absent. These changes are indicative of a pancreatitis caused by an infection.

Outcome

In acute pancreatitis with acinar necrosis the outcome seems to be favorable in most cases, since the cases that have been reported so far showed a mild pancreatitis[17].

Outcome

The outcome of acute pancreatitis with duct epithelium necrosis is largely unknown because the patients in whom this necrosis pattern has been observed and described all died from prolonged circulatory failure

Figure17.6 Acute pancreatitis with acinar cell necrosis pattern.

Intralobular focus of acinar necrosis surrounded by few granulocytes and macrophages.

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