24+pancreas Pancreatitis+-+update

Pancreas and Pancreatitis
LEARNING OBJECTIVES
• Define the endocrine and exocrine functions of the pancreas

• Illustrate the physiology of pancreatic enzyme secretion
• Outline the criteria of acute pancreatitis
• Create a diagnostic workup for a patient presenting with new onset
acute pancreatitis
• Categorize the complications of acute and chronic pancreatitis
PANCREAS
Serves as both an endocrine and exocrine organ
• Endocrine function
• Composed of the islets of Langerhans,
comprising 1-2% of the pancreas
• Secretes insulin, glucagon and somatostatin
• Exocrine function
• Composed of acinar cells, make up 80-85% of
the organ mass
• Secrete zymogens, or proenzymes, which
must be activated in the intestine
Source: https://www.neuroendocrinecancer.org.uk/pancreas-pei-pert/
PANCREAS
Pancreatic development
• During normal development, the dorsal and ventral buds of the
pancreas fuse and drain through the papilla of Vater via the duct of
Wirsung
• Pancreatic divisum
• Most common anomaly, found in 3-10% of people
• Derived from fusion failure of the ventral and dorsal pancreatic
buds during development
• Causes most of the pancreatic exocrine enzymes to be released
into the duodenum through the smaller minor papilla via the duct
of Santorini
PANCREAS
© 2020 Elsevier, Inc. All Rights Reserved. Robbins and Cotran Pathologic Basis of Disease.
PANCREAS
Pancreatic developmental anomalies

• Annular pancreas: pancreas encircles the duodenum; can cause
small bowel obstruction
© 2020 Elsevier, Inc. All Rights Reserved. The Developing Human.

PANCREAS
Pancreatic enzyme function

• Many exocrine enzymes secreted from the pancreas are created in an inactive
form (zymogens)
• Trypsinogen is one of these zymogens, which is activated by enterokinase in the
small bowel, into trypsin
• The remainder of the zymogens are activated by trypsin in the duodenum
• Once activated, these enzymes break down protein, fat and carbohydrates in
the intestinal tract
• This process protects the pancreas from being degraded by the activity of these
enzymes
PANCREAS
© 2020 Elsevier, Inc. All Rights Reserved. Netter‘s Gastroenterology.

PANCREAS
Important pancreatic enzymes

• Protein/peptide degradation • Lipid degradation
• Trypsinogen • Lipase (active enzyme)
• Chymotrypsinogen • Procolipase
• Proelastase • Prophospholipase A2
• Nucleotide degradation
• Procarboxypeptidase
• Deoxyribonuclease (DNAse)
• Carbohydrate degradation • Ribonuclease (RNAse)
• Amylase (active enzyme)
ACUTE PANCREATITIS
• Definition: acute inflammatory process of the pancreas

• Incidence: 5-35 cases/100,000 people per year; significant cause of
gastroenterology admissions to the hospital and health system costs
• Etiology
• Caused by early and inappropriate activation of trypsin within the
pancreas
• This leads to activation of zymogens into active enzymes in the
pancreatic parenchyma
• Inappropriate activation of enzymes induces autodigestion of
acinar cells and pancreatic tissue
ACUTE PANCREATITIS
Common causes of pancreatitis

• Gallstones 40-70% of cases (most common cause)
• Alcohol abuse 25-35% of cases (second more common cause)
• Hypertriglyceridemia
• Post-ERCP procedure • Autoimmune pancreatitis
• Genetic predisposition • Vascular disease
• Medications • Infections
• Pancreatic duct injury • Toxins
• Biliary obstruction • Anatomic abnormalities
• Hypercalcemia • Idiopathic
MECHANISMS OF PANCREATITIS
© Kumar, V., Abbas, A.K., & Aster, J.C. (2018). Robbins Basic Pathology. (10th ed.)
ACUTE PANCREATITIS
Gallstone pancreatitis
• Epidemiology: Majority of cases of
acute pancreatitis
• Mechanism: gallstone impacted at
the ampulla of Vater
• Diagnosis: presence of gallstones
on ultrasound; no need for
Obstruction
ERCP/EUS unless signs of
cholangitis
• Prevention: cholecystectomy,
ideally during same hospitalization
Image Modified from the Public Domain.
ACUTE PANCREATITIS
Alcohol pancreatitis
• Epidemiology: occurs in up to 10% of patients who chronically
consume alcohol
• Mechanism: thought to be caused by sensitization of acinar cells to
hormonal signals, causing increased enzyme production and
activation
• Prevention: decrease/cease alcohol consumption
ACUTE PANCREATITIS
Hypertriglyceridemia pancreatitis
• Epidemiology: 1-14% of cases of acute pancreatitis
• Risk factors:
• Serum triglycerides > 1000 mg/dL
• Genetics
• Obesity, diabetes, hypothyroidism, pregnancy
• Mechanism: breakdown of triglycerides into toxic free fatty acids by
pancreatic lipase causes an inflammatory response
• Treatment: can use insulin or plasma exchange for severe cases
• Prevention: decrease triglycerides with fibrates, statins, and/or
omega-3 fatty acid supplementation
ACUTE PANCREATITIS
Autoimmune pancreatitis
• Epidemiology: unclear prevalence, increasingly recognized worldwide
• Clinical presentation: can present with recurrent bouts of acute
pancreatitis and/or chronic pancreatitis
• Diagnosis:
• Labs showing elevated IgG4;
• Pancreas biopsy with IgG4 positive plasma cells
• Imaging with diffusely enlarged pancreas and/or biliary/pancreatic duct
strictures
• Treatment: typically responds to glucocorticoids
ACUTE PANCREATITIS
Infections and toxins

• Bacterial: Mycoplasma, Leptospirosis, Salmonella, Legionella
• Viral: Mumps, Coxsackievirus, HSV, CMV, VZV, HIV, Hep B
• Fungal: Aspergillus
• Parasites: Toxoplasma, Cryptosporidium, Ascaris
• Toxins: Brown recluse spider bite, scorpion sting, Gila monster lizard
bite
ACUTE PANCREATITIS
Clinical presentation
• Symptoms:
• Acute severe epigastric pain with radiation to the back
• Nausea/vomiting
• Severe cases: fever, dyspnea
• Physical exam:
• Abdominal tenderness to palpation, particularly in the
epigastrium
• Scleral icterus in cases with concurrent biliary obstruction
• In severe cases can present with fever, hypoxia, hypotension
ACUTE PANCREATITIS
Categorization by severity
• Mild: absence of systemic or local complications; no end organ
dysfunction
• Moderate: less than 48 hours of end organ dysfunction
• Severe: persistent end organ dysfunction (>48 hours)

ACUTE PANCREATITIS
Diagnosis
• Labs:
• Elevated serum amylase and lipase > 3x ULN
• Can have leukocytosis and polycythemia due to hemoconcentration
↑
RBC
• Imaging:
• Abdominal CT: diffusely enlarged pancreas with
heterogeneous enhancement; surrounding fat stranding
• Formal diagnosis: 2/3 of the following features
1. Classic abdominal pain
2. Elevated serum amylase or lipase > 3x ULN
3. Evidence of acute pancreatitis on imaging
ACUTE PANCREATITIS
Treatment
• Fluid replacement: aggressive IV fluid resuscitation to replace
intravascular fluid losses
• Pain control
• Hemodynamic monitoring
• Early oral feeding as tolerated -> if significant vomiting can
consider placement of nasogastric tube for gastric
decompression; parenteral nutrition is only provided if enteral
feeding is not tolerated for multiple days
• Address underlying cause (previous slides)
ACUTE PANCREATITIS
Local complications of pancreatitis

Pancreatic pseudocysts are collections of leaked pancreatic
• Pancreatic pseudocyst fluids. They may form next to the pancreas during
pancreatitis.
• Acute peripancreatic fluid collection

• Acute necrotic collection
• Infected necrosis
• Splanchnic vein thrombosis
• Pseudoaneurysm ->
• Abdominal compartment syndrome
CHRONIC PANCREATITIS
• Definition: progressive inflammatory changes in the pancreas

leading to destruction of the parenchyma and loss of endocrine and
exocrine function
• Epidemiology: prevalence of 50/100,000 people
• Etiology and risk factors
• Alcohol: most common risk factor globally
• Smoking
• Hypertriglyceridemia
• Genetic risk factors
• Autoimmune pancreatitis
• Chronic obstruction or recurrent acute pancreatitis
Pancreatic
fibrosis
Pancreatic
calcifications
© 2020 Elsevier, Inc. All Rights Reserved. Netter‘s Gastroenterology.

Treatment
• Pain control:
• Cessation of alcohol intake
• Small low fat meals
• Smoking cessation
• Pancreatic enzyme supplementation
• Analgesia: amitriptyline, pregabalin; may require opioids for long-
term control
• Local nerve blocks
• Endoscopic therapy/surgery
• Loss of pancreas function
• Exocrine enzymes, insulin
Complications of chronic pancreatitis

• Pancreatic pseudocyst
• Pseudoaneurysm: erosion of pseudocyst into blood vessel
leading to GI bleeding
• Biliary or duodenal obstruction
• Pancreatic ascites or pleural effusions: fistula formation
between the pancreatic duct within the abdomen or with the
pleural space
• Splenic vein thrombus
• Pancreatic cancer: at higher risk due to chronic inflammation
• Diabetes from insulin deficiency
TAKE HOME POINTS
• The pancreas is both an endocrine and exocrine organ,

secreting critical hormones and enzymes for digestion and
homeostasis
• Acute pancreatitis is a common disease, featuring inappropriate
activation of enzymes in the pancreas, leading to autodigestion
• Common causes of acute pancreatitis include alcohol use,
gallstones, and elevated triglycerides
• Chronic pancreatitis is the result of repeated inflammation of the
pancreas causing fibrosis and loss of endocrine and exocrine
functions

24+pancreas Pancreatitis+-+update

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Pancreas and Pancreatitis

• Define the endocrine and exocrine functions of the pancreas

Serves as both an endocrine and exocrine organ

Pancreatic developmental anomalies

© 2020 Elsevier, Inc. All Rights Reserved. The Developing Human.

Pancreatic enzyme function

© 2020 Elsevier, Inc. All Rights Reserved. Netter‘s Gastroenterology.

Important pancreatic enzymes

• Definition: acute inflammatory process of the pancreas

Common causes of pancreatitis

Infections and toxins

• Viral: Mumps, Coxsackievirus, HSV, CMV, VZV, HIV, Hep B

• Parasites: Toxoplasma, Cryptosporidium, Ascaris

• Moderate: less than 48 hours of end organ dysfunction

• Severe: persistent end organ dysfunction (>48 hours)

Local complications of pancreatitis

• Acute peripancreatic fluid collection

• Definition: progressive inflammatory changes in the pancreas

© 2020 Elsevier, Inc. All Rights Reserved. Netter‘s Gastroenterology.

Complications of chronic pancreatitis

• The pancreas is both an endocrine and exocrine organ,

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