[Management of Acute Pancreatitis]

By

ACKNOWLEDGEMENT

I would take this opportunity to thank my research supervisor, family and friends for their support and guidance without which this research would not have been possible.



DECLARATION

I [type your full first names and surname here], declare that the contents of this dissertation/thesis represent my own unaided work, and that the dissertation/thesis has not previously been submitted for academic examination towards any qualification. Furthermore, it represents my own opinions and not necessarily those of the University.

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ABSTRACT

Over the past decades several epidemiological studies have been published reporting on incidence trends, hospital admissions, etiological factors and outcome of both acute and chronic pancreatitis. Over time, the incidence of acute pancreatitis has increased in the Western countries. Also, the number of hospital admissions for both acute and chronic pancreatitis has increased. These upward time trends possibly reflect a change in the prevalence of main etiological factors (e.g. gallstones and alcohol consumption) and cofactors such as obesity and genetic susceptibility. Acute and chronic pancreatitis is associated with significant morbidity and mortality and a substantial use of health care resources. Although the case-fatality rate of acute pancreatitis decreased over time, the overall population mortality did not change for both acute and chronic pancreatitis. This is the first comprehensive description of the proteome of mesenteric lymph during acute pancreatitis and has demonstrated a significantly increased relative abundance of 7 secreted pancreatic catabolic enzymes in acute pancreatitis conditioned mesenteric lymph. This study provides a clear rationale for further research to investigate the efficacy of enteral protease inhibitors in the treatment of acute pancreatitis.

Table of Contents

ABSTRACT1

CHAPTER I: INTRODUCTION3

CHAPTER II: METHODS5

Research Design5

Acute pancreatitis5

Epidemiology6

CHAPTER III: RESULTS8

First attack of acute pancreatitis8

Hospital admissions for acute pancreatitis11

Age, sex and racial distribution12

Recurrent acute pancreatitis14

Aetiology of acute pancreatitis15

Outcome and case-fatality of acute pancreatitis18

Chronic pancreatitis21

Epidemiology22

Incidence and prevalence of chronic pancreatitis22

Hospital admissions for chronic pancreatitis23

Age, sex and racial distribution25

Aetiology of chronic pancreatitis26

Natural course and outcome of chronic pancreatitis29

CHAPTER IV: DISCUSSION33

CHAPTER V: CONCLUSION41

REFERENCES48

The Management of Acute Pancreatitis to Reduce the Mortality Rate within the Disease

CHAPTER I: INTRODUCTION

Acute pancreatitis is a common inflammatory disease that remains a significant clinical challenge. For the third of patients who develop severe acute pancreatitis, the risk of mortality remains high at 20-30% despite improvements in resuscitation and intensive care support . The mortality is due to multiple organ failure, and this has a bimodal time course distribution. Early deaths, during the first week, are due to a fulminant cytokine mediated systemic inflammatory response syndrome and multiple organ dysfunction (MODS), without an overt septic focus. Later deaths, after 2 or more weeks, are due to MODS associated with infection of necrotic pancreas. Many pathophysiological processes in acute pancreatitis have been described, but the critical factors that drive the MODS have yet to be fully elucidated.

There is a body of experimental work, largely derived from rodent studies, suggesting that mesenteric lymph, collected during critical illness, contains toxic factors that contribute to the development of MODS and might be more important than translocated bacteria ...