panc Flashcards
The pancreas is a soft, elongated, flattened gland that is 12 to 20 cm in length.
The adult gland weighs between 70 and 110 g.
The pancreas is coarsely lobulated and covered with fine connective tissue, without a true capsule. It is primarily retroperitoneal, lying approximately at the level of the L1-L2 lumbar vertebrae lying
approximately at the level of the L1-L2 lumbar vertebrae.
head of the pancreas is on the right, lying within the curvature of the duodenum, and the remainder of the pancreas lies obliquely in the posterior abdomen, with the tail extending as far as the gastric surface of the spleen
The anterior surface of the head of the pancreas is adjacent to the pylorus, the first part of the duodenum, and the transverse colon.
The posterior surface abuts the hilum7 and medial border of the right kidney, the inferior vena cava and the right renal vessels, the right gonadal vein, and the right crus of the diaphragm
The uncinate process (lingula) is a prolongation of pancreatic tissue that projects off the lower part of the pancreatic head, extending upward and to the left. The uncinate process lies anterior
to the aorta and inferior vena cava and is covered superiorly by the superior mesenteric vessels that emerge below the neck of
the pancreas.
The neck of the pancreas is a constricted part of the gland, extending from the head of the pancreas toward the left to connect the head with the body of the pancreas. It is 1.5 to 2 cm long and 3 to 4 cm wide.
Posterior to the neck of the pancreas lies the confluence of the portal vein with the superior mesenteric and splenic veins.
Anteriorly it is covered in part by the pylorus
and peritoneum of the lesser sac. The neck extends to the right as far as the anterosuperior pancreaticoduodenal artery from the
gastroduodenal artery
The body of the pancreas runs toward the left side, anterior to the aorta.
It is retroperitoneal and held against the aorta by the
peritoneum of the lesser sac. The anterior surface of the body is covered by peritoneum of the omental bursa, which separates the stomach from the pancreas.
The antrum and body of the stomach and the transverse mesocolon contact the body anteriorly.
Posterior to the body of the pancreas are the aorta, the origin of the superior mesenteric artery, the left crus of the diaphragm, the left kidney, the left adrenal gland, and the splenic vein.
Posterior to the body of the pancreas are the aorta, the origin of the superior mesenteric artery, the left crus of the diaphragm, the left kidney, the left adrenal gland, and the splenic vein.
The tip of the tail is intraperitoneal lying
between layers of the splenorenal ligament. The relationship of the pancreas to important structures in the posterior abdomen is seen
The main pancreatic duct (of Wirsung) begins near the tail of the pancreas. It is formed from anastomosing ductules draining the lobules of the gland. It courses left to right and is enlarged by additional ducts.
Through the tail and body, the duct lies midway
between the superior and inferior margins and slightly posterior.
The main duct turns caudal and posterior on reaching the head of the pancreas. At the level of the major papilla, the duct turns horizontally to join in most cases with the bile duct
The duct of Wirsung and the common bile duct empty into the duodenum obliquely via the major papilla. The ampulla of Vater is the common pancreaticobiliary channel within the papilla where the 2 ducts come together, separated by common adventitia
The proximal portion of the embryonic dorsal pancreatic duct remains patent in about 70% of adults and empties through the accessory papilla
Pancreas divisum. The embryonic dorsal and ventral ducts fail to fuse.
Most of the pancreatic secretion empties through the accessory papilla. Only pancreatic secretions from the uncinate process and part of the head of the pancreas
The length of the common channel (when present)
averages 4.5 mm, with a range of 1 to 12 mm
Three circular muscle bundles, collectively called the sphincter of Oddi, act as sphincters encircling each duct as well as the ampulla of Vater.
two thirds to three quarters of the general population
has a common channel, whereas about one fifth have completely separate openings and just under 10% have an interposed sputum that separates the 2 ducts.
Long common channels or pancreaticobiliary
malunion can predispose to pancreatitis or biliary cancer
Approximately 70% of the general population has a patent accessory duct (of Santorini), which is also known as the minor duct
The accessory duct lies anterior to the bile duct and drains into the minor papilla, which lies proximal to the major papilla, but is also located in the second portion of the duodenum.
Up to 10% of people have an interruption between
the major papilla and the main duct, with drainage into the duodenum occurring via the minor papilla; this variant is called pancreas divisum
The main pancreatic duct is widest at the head of the pancreas, and the duct gradually tapers as it progresses to the tail
Upper limits of normal for the pancreatic duct diameter in the head (5 mm), body (4 mm), and tail (3 mm) are generally accepted
The pancreas has a rich circulation that is derived from branches of the celiac and superior mesenteric arteries.
The head of the pancreas and surrounding duodenum are supplied by 2 pancreaticoduodenal
arterial arcades.
They are formed by the anterior and
posterior superior pancreaticoduodenal arteries from the hepatic branch of the celiac artery that join a second pair of anterior and posterior inferior pancreaticoduodenal arteries branching from the superior mesenteric artery
The course of the splenic artery is posterior to the body and tail and loops above and below the superior margin of the pancreas.
It gives off the dorsal pancreatic artery, which usually joins one of the posterior superior arcades after giving off the inferior pancreatic artery
The caudal pancreatic artery arises from the left gastroepiploic artery or from a splenic branch at the spleen.
It joins with branches of the splenic and great pancreatic arteries and other pancreatic arteries.
It flows into the portal venous system, which is formed by the joining of the superior mesenteric and splenic veins at the confluence behind the neck of the pancreas.
The portal vein lies behind the pancreas and in front of the inferior vena cava.
The common bile duct lies anterior to the portal
vein with the hepatic artery to the left of the common bile duct.
The splenic vein originates at the hilum of the spleen and curves behind the tail of the pancreas and below the splenic artery, to the right along the posterior surface of the pancreas
The pancreatic veins drain the neck, body, and tail of the pancreas and join the splenic vein. The pancreaticoduodenal veins lie close to their corresponding arteries and empty into the splenic or portal veins.
small periacinar and perilobuar capillary
networks that drain into larger ducts alongside pancreatic
blood vessels
The superior lymphatic vessels run along the
upper border of the pancreas closely with the splenic blood vessels, whereas inferior lymphatic vessels run with the inferior pancreatic artery.
Superior and inferior lymphatic vessels draining the left pancreas, including the tail of the pancreas and left half of the body empty into nodes in the splenic hilum.
The visceral efferent innervation of the pancreas is through the vagi and the splanchnic nerves by way of the hepatic and celiac plexuses.
The efferent fibers of the vagi pass through
these plexuses without synapsing and terminate in parasympathetic ganglia found in the interlobular septa of the pancreas.
The visceral efferent innervation of the pancreas is through the vagi and the splanchnic nerves by way of the hepatic and celiac plexuses.
The bodies of the postganglionic sympathetic
neurons are in the great plexuses of the abdomen.
Their postganglionic fibers innervate only blood vessels. The autonomic fibers, both efferent and afferent, are located in proximity to the blood vessels of the pancreas. The vagi also carry some visceral afferent fibers
The basic subunit of the exocrine portion is the acinus,
which is at its base a spherical mass of dark-staining secretory cells called acinar cells
The spherical acinus connects to a goblet-shaped neck that is composed of tubular cells called
duct cells.
The inner lumen of the acinus forms the terminal portion of the secretory duct
The pancreatic ductal system is nonstriated and is lined by columnar epithelium
acinar cells are tall pyramidal or columnar
epithelial cells, with their broad bases on a basal lamina and their apices converging on a central lumen. In the resting state, numerous eosinophilic zymogen granules fill the apical portion of the cell.
The basal portion of the cells contains 1 or 2 centrally
located, spherical nuclei and basophilic cytoplasm.
The most prominent feature of the acinar cell is the dense zymogen granules that are concentrated in the apical pole.
Rough ER occupies about 20% of the cell volume
It takes up most of the basal region of the acinar cells and interdigitates with the zymogen granules in the apical region. This abundance of rough ER allows the acinar cell to synthesize more protein than any
other parenchymal cell in the body.
centroacinar cells, bridge acinar cells with the ductal epithelium.
These centroacinar cells are pale-staining on H&E staining and smaller than the acinar cells.
The collagen fibers and other extracellular matrix proteins are secreted by a less common resident cell type, the pancreatic stellate cell (PSC).
The islets of Langerhans number about 1 million in the human pancreas
There are 5 major cell types in the endocrine pancreas.
Beta cells are the most numerous, constituting about 50% to 80% of the islets. They secrete insulin and amylin.
PP cells, also known as F cells, make up 10% to 35% and secrete pancreatic polypeptide and adrenomedullin.
Alpha cells make up 5% to 20% and secrete glucagon. The remaining 5% consists of delta cells, which secrete
somatostatin, and epsilon cells, which secrete ghrelin.
Other rarer subpopulations of islets make additional hormones such as galanin.
The pancreas arises from posterior foregut endoderm
Two buds form: 1 dorsal and 1 bi-lobed ventral bud.
About a month into gestation, the foregut evaginates into a condensation of overlying mesenchyme to form the first morphologic evidence of the dorsal bud.
About a week later, a ventral bud forms as an outpouching of hepatic diverticulum. The ventral bud has a bilobed origin, of which the left ventral bud gradually regresses.
Both dorsal and ventral buds undergo elongation of a stalk region and branched morphogenesis
At 37 to 42 days into gestation, as the duodenum grows, the ventral pancreas rotates around the duodenum and fuses with the dorsal pancreas
The dorsal pancreas forms the tail, body, and superior portion of the pancreatic head. It also contains the dorsal duct that forms the distal portion of the main pancreatic duct (of Wirsung) and the entire minor accessory duct (of Santorini).
The ventral pancreas forms the uncinate process and the inferior part of the head.
The ventral pancreas’s ventral duct forms the proximal portion of the main pancreatic duct (of Wirsung).
As mentioned earlier, the 2 duct systems corresponding to the ventral and dorsal buds fail to fuse in up to 10% of the general population
pancreas divisum, the accessory duct functions as the main conduit for drainage of pancreatic juice
The clinical significance of pancreas divisum is discussed later. Failure of the ventral pancreas to fully rotate around the duodenum, or persistence of the left ventral bud can lead to an annular pancreas, also discussed later
Failure of the ventral pancreas
to fully rotate around the duodenum, or persistence of the left ventral bud can lead to an annular pancreas
After the pancreatic buds fuse, the cellular architecture of the pancreas rapidly expands.
Notably, all 3 functionally distinct parenchymal cell types—acinar, duct, and islet cells—differentiate
from a common pancreatic progenitor lineage.
The first, termed the primary transition,
is defined as the conversion of predifferentiated cells to a protodifferentiated state in which low levels of pancreas-specific proteins are present.
The second phase, or the secondary transition,
is marked by a dramatic rise in pancreatic cell number and pancreas- specific protein synthesis, as well as an acceleration in both exocrine and endocrine differentiation
Annular pancreas is a congenital anomaly in which a portion of the pancreas forms a thin band around the preampullary portion of the duodenum, leading to complete or partial bowel obstruction
Although annular pancreas is often diagnosed prenatally or during infancy, it is erroneous to consider it solely a disease of infancy.
A second peak of detection occurs in the fourth through seventh decades of life
Pancreas divisum (PD) results from a failure of the dorsal and ventralpancreatic ducts to fuse during embryogenesis resulting in the majority of exocrine secretions draining from the relatively smaller dorsal duct of Santorini and minor papilla
3 types of pancreas divisum identified
Classic or complete divisum, in which there is complete failure of fusion between the dorsal duct (Santorini) and ventral duct (Wirsung), occurs in 71% of patients with PD.
The second type of PD called dominant type or dorsal duct pancreas divisum, in which there is absence of the ventral duct, occurs in 6% of patients with divisum
The last type, incomplete pancreas divisum, in which there remains a small communication between the ventral and dorsal ducts, occurs in 23% of patients
Ectopic (heterotopic) pancreatic tissue, often referred to as a pancreatic rest
Pancreaticobiliary malunion (PBM) is a congenital malformation in which a common channel for bile and pancreatic fluid is formed, owing to the absence of a septum between the ducts
The abnormal union occurs outside the duodenal wall; thus the influence of the sphincter of Oddi is lost, allowing reflux of pancreatic exocrine secretions into the biliary system, and bile into the pancreatic duct.
markedly elevated amylase concentration can be detected in the bile of patients with a common channel of 5 mm or greater
Biliary neoplasms are most frequently
seen in the gallbladder;
however, bile duct neoplasms can also occur with increased risk in presence of congenital biliary dilation, 32.1%, versus 7.3% in patients without biliary dilation
A classification for PBM has been proposed by dividing it into 3 types:
a pb type, in which the pancreatic duct appears to join
the bile duct;
a bp type, in which the insertion of the bile duct is into the pancreatic duct
a Y type, in which there is a long common channel measuring greater than 15 mm in length
In large series, the bp and pb types have each been reported to be the most common type of PBM
Pancreaticobiliary malunion is diagnosed by traditional cholangiography (ERCP, intraoperative cholangiography, or percutaneous cholangiography), MRCP, or helical CT scan. Traditional cholangiography remains the gold standard
The functional unit of the exocrine pancreas is composed of anacinus and its draining ductule
The ductal epithelium extends to the lumen of the acinus, with the centroacinar cell situated as an extension of the ductal epithelium into the acinus
The centroacinar cell plays a key role in providing
progenitor cells for pancreatic cell lineages
The ductule drains into interlobular (intercalated) ducts, which in turn drain into the main pancreatic ductal system.
The duct epithelium consists of cells that are cuboidal to pyramidal and contain the abundant mitochondria necessary for energy products needed for ion transport
The duct cells as well as the centroacinar cells contain carbonic anhydrase, which is important for their ability to secrete bicarbonate
The purposes of the water and ion secretions are
to deliver digestive enzymes to the intestinal lumen and to help neutralize gastric acid emptied into the duodenum
Pancreatic juice secreted during stimulation with secretin is clear, colorless, alkaline, and isotonic with plasma.
The flow rate increases from an average rate of 0.2 or 0.3 mL/min in the resting (interdigestive) state to 4.0 mL/min during postprandial stimulation.
The total daily volume of secretion is 2.5 L
pancreas is stimulated by secretin (the major mediator of the greater volume output), bicarbonate and chloride concentrations change reciprocally
Secretin stimulates secretion by binding to its receptor on the basolateral membrane of the duct cell, thus activating adenylate cyclase and increasing cyclic adenosine monophosphate (cAMP);
acetylcholine does so by binding to its receptor and
raising intracellular calcium concentrations.
Human amylase is secreted by both the pancreas and salivary
glands. These enzymes digest starch and glycogen in the diet.
Salivary amylase initiates
digestion in the mouth and may account for a significant portion of starch and glycogen digestion because it is transported with the meal into the stomach and small intestine, where it continues to have activity.
In the stomach, the amylase activity is protected from secreted gastric acid by buffering from the meal and by the
protected alkaline environment of salivary and gastric mucus.
The pancreas secretes 3 lipases: lipase (or TG lipase), prophospholipase A2, and carboxylesterase
Salivary (lingual) and gastric lipases also contribute to fat digestion but in a minor fashion
Pancreatic lipase binds to the oil-water interface of the TG oil droplet, where it acts to hydrolyze a TG molecule to 2 fatty
acid molecules released from carbons 1 and 3 and a monoglyceride with a fatty acid esterified to glycerol at carbon
Bile acids aid in the emulsification of TG to enlarge the surface area for lipase to act on, and they form micelles with fatty acids and monoglycerides, which in turn remove these products from the oil-water interface.
Colipase is believed to form a complex with lipase and bile salts. This ternary complex anchors lipase and allows it to act in a more hydrophilic environment
on the hydrophobic surface of the oil droplet.
Phospholipase A2 catalyzes the hydrolysis of the fatty acid ester linkage at carbon 2 of phosphatidylcholine.
This cleavage leads to the formation of free fatty acid and lysophosphatidylcholine
The pancreas secretes a variety of proenzyme proteases that are activated in the duodenum by trypsin
Trypsin, chymotrypsin, and elastase are endopeptidases that cleave specific
peptide bonds adjacent to specific amino acids
carboxypeptidases, which are
exopeptidases that cleave peptide bonds at the carboxyl terminus of proteins
The combined actions of gastric pepsin and the pancreatic proteases result in the formation of oligopeptides and free amino
acids. The oligopeptides can be further digested by enterocyte brush-border enzymes
These amino acids have greater effects on stimulating pancreatic secretion, inhibiting gastric emptying, regulating small bowel motility, and causing satiety.
The vagal nerves mediate the cephalic phase of the exocrine secretion.
Acetylcholine is certainly a major neurotransmitter involved in mediating cephalic phase pancreatic secretion because cholinergic antagonists greatly reduce and in some cases abolish sham
feeding–stimulated pancreatic secretion in humans
Nerve endings containing the peptides VIP, GRP, CCK, and enkephalins have been identified in the pancreas
gastric phase of pancreatic secretion results from meal stimuli acting in the stomach.
The major stimulus is gastric distention,
which causes predominantly secretion of enzymes with little secretion of water and bicarbonate
Three gastric processes—secretion of acid, pepsin, and lipase; digestion; and emptying—are tightly coupled
to the mechanisms of the intestinal phase of pancreatic secretion
The intestinal phase begins when chyme first enters the small intestine from the stomach
It is mediated by hormones and
enteropancreatic vagovagal reflexes.
Secretin is released from enteroendocrine
S cells in the duodenal mucosa when the pH of the lumen is less than 4.5
The most potent amino acids for stimulating pancreatic secretion in humans are phenylalanine, valine, methionine, and tryptophan.
Truncal vagotomy and atropine markedly inhibit the enzyme (and bicarbonate)
responses to low intestinal loads of amino acids and fatty acids, as well as to infusion of physiologic concentrations of CCK.
These results indicate that vagovagal reflexes mediate enzyme secretion and augment bicarbonate secretion stimulated by secretin.
CCK is the major humoral mediator of meal-stimulated enzyme secretion during the intestinal phase. The circulating
concentration of CCK rises with a meal
Pancreatic Secretory Function Tests
Secretin Measurements of volume and
HCO3– secretion into the
duodenum after IV secretin
Provide the most sensitive and specific
measurements of exocrine pancreatic
function
Require duodenal intubation and IV administration of hormones; not widely available
Detection of mild, moderate, or severe exocrine pancreatic dysfunction
CCK
Measurements of duodenal outputs of amylase, trypsin, chymotrypsin, and/or lipase after IV CCK
Secretin and CCK
Measurements of volume,
HCO3 −, and enzymes after IV secretin and CCK
Indirect (Requiring Duodenal Intubation)
Lundh test meal Measurement of duodenal
trypsin concentration after oral ingestion of a test meal
Does not require IV administration of
hormones
Indirect (Tubeless)
Fecal fat Measurement of fat in the stool
after ingesting meals with a known amount of fat
Provides a quantitative measurement of
steatorrhea
Fecal Elastase 1
NBT-PABA
Oral ingestion of NBT-PABA or fluorescein dilaurate with a meal, followed by
measurements of PABA or
fluorescein in serum or urine
The most common known causes of Acute Pancreatitis in children are biliary tract disease (10% to 30%), medications (25%), systemic disease (33%), trauma
(10% to 40%), metabolic disease (2% to 7%), and HP (5% to
8%); 13% to 34% of cases are idiopathic
Pancreas divisum is the most common anatomic aberration, although a wide variety of other structural abnormalities of
the bile and pancreatic duct also have been observed
AP is the most common pancreatic disease,
whereas pancreatic cancer is the most lethal
This increase is presumably—as in adults—due to the rise in obesity-associated cholelithiasis.
2012 Atlanta Classification Revision of Acute Pancreatitis
MILD ACUTE PANCREATITIS
No organ failure
No local or systemic complications
MODERATELY SEVERE ACUTE PANCREATITIS
Transient organ failure (<48 hr) and/or
Local or systemic complications* without persistent organ failure
SEVERE ACUTE PANCREATITIS
Persistent organ failure (>48 hr) single organ or multiorgan
*Local complications are peripancreatic fluid collections, pancreatic necrosis and peripancreatic necrosis (sterile or infected), pseudocyst, and walled- off necrosis (sterile or infected).
AP is now defined by a patient meeting 2 of the following 3 criteria:
(1) symptoms (e.g., acute onset epigastric and/or left upper quadrant pain, often radiating to the back) consistent with pancreatitis
(2) a serum amylase or lipase level greater than 3 times the uppe limit of the laboratory’s reference range, and
(3) radiologic imaging consistent with pancreatitis, usually using CT or MRI
Pancreatitis is classified as acute unless there are findings on CT, MRI, EUS, or ERCP suggestive of chronic pancreatitis.
If such findings are present, pancreatitis is classified as chronic pancreatitis, and any further episode of AP is considered an exacerbation of chronic pancreatitis
Mild AP, the most common form, has no associated organ failure, no local or systemic complications, and usually resolves in the first week.
Moderately severe AP is defined by the presence of transient organ failure (lasting <48 hours) and/or local complications.
Severe AP is defined by persistent organ failure (lasting >48 hours).
Local complications include acute peripancreatic fluid collections,
acute necrotic collections (pancreatic and peripancreatic necrosis, sterile or infected), pseudocyst, and walled-off necrosis
(WON; sterile or infected
Markers of severe pancreatitis include 3 or more of Ranson’s 11 criteria for non-gallstone pancreatitis and an
Acute Physiology and Chronic Health Evaluation (APACHE-II) score above 8
hemorrhagic pancreatitis is not a synonym for necrotizing pancreatitis.
When occurring early in the course, bleeding may be due to venous bleeding from the severe inflammatory process
severe, hemorrhage is more commonly associated with pseudoaneurysm formation leading to hemorrhagic collections or hemoperitoneum.
Interstitial pancreatitis accounts for nearly
75% to 80% of the cases and, on contrast-enhanced CT scan in such patients, the pancreas is perfused well, without any nonperfused, low attenuation areas.
Necrotizing pancreatitis according to the revised Atlanta classification includes both pancreatic and/or peripancreatic necrosis.
Pancreatic necrosis is diagnosed on CT scan when ≥30% of the pancreatic parenchyma is low-attenuating or nonenhancing.
Acute peripancreatic fluid collections are seen as low attenuation areas around the pancreas.
If these collections cross the fascial
planes like Gerota fascia, then one should consider them as acute peripancreatic necrotic collections rather than simple fluid collections.
Approximately 30% to 50% of cases of AP, mainly the interstitial type, have peripancreatic fluid collections, which
typically resolve.
After a period of approximately 4 weeks, if the acute peripancreatic fluid collections persist and develop a wall, then they are called a “pseudocyst.”
Pseudocysts are located adjacent to or off the body of the pancreas
Necrotic collections, which may also be peripancreatic, develop a wall after 4 weeks and are then referred to as WON
WON is pancreatic necrosis that has liquefied after 5 to 6 weeks
Similar to a pseudocyst, a wall develops. However, whereas a pseudocyst always contains fluid, pancreatic necrosis, even if walled off early, contains a
significant amount of debris that only becomes liquefied after 5 to 6 weeks.
Draining WON too early (before 4 weeks) is discouraged because the debris is typically thick, often with the consistency of rubber, early in the course of the disease.
After 4 weeks, WON can be treated similarly to a pseudocyst and drained surgically, endoscopically, or percutaneously
Most organ failure observed in the first week is also present on day 1, and at that time, one should consider (and treat) the patient as having severe AP.
If the organ failure persists beyond 48 hours, severe AP is confirmed.
If organ failure resolves within 48 hours and local complications evolve, the case would be classified as moderately severe AP
If no local complications are seen, the revised Atlanta classification still classifies the patient as moderately severe pancreatitis; however, the original description of moderately severe AP described patients with local complications but without organ failure
The second phase usually starts after 7 days and is mainly characterized by the local complications and ensuing infection of such local complications. The organ failure seen in the first phase may continue and contribute to late morbidity and mortality, usually with infected necrosis
Organ failure occurs in ∼5% of interstitial pancreatitis
Factors Associated With Severe Acute Pancreatitis
PATIENT CHARACTERISTICS
Age >55 yr
Obesity (BMI >30 kg/m2)
Altered mental status
Comorbid disease
Systemic inflammatory response syndrome (SIRS)
Two or more of the following (SIRS criteria)
Pulse >90/min
Respirations >20/min or PaCO2 <32 mm Hg
Temperature >38°C or <36°C
WBC count >12,000 or <4000/mm3 or >10% band forms
LABORATORY FINDINGS
BUN >20 mg/dL or rising BUN level
Elevated serum creatinine level
Hematocrit >44% or rising hematocrit
IMAGING FINDINGS
Pleural effusion(s)
Pulmonary infiltrate(s)
Multiple or extensive extrapancreatic fluid collections
Approximately 75% to 80%, of patients with AP have a resolution of the disease process (interstitial pancreatitis) and do not enter a second phase.
However, in ∼20% of patients, a more protracted
course develops, typically related to the necrotizing process (necrotizing pancreatitis) lasting weeks to months.
There are 2 time peaks for mortality in AP. Most studies in the USA and Europe reveal that about half the deaths occur within the first week or 2, usually from multiorgan failure
The initial step in the pathogenesis of AP is conversion of trypsinogen to trypsin within acinar cells in sufficient quantities to overwhelm normal mechanisms to remove active trypsin
Trypsin, in turn, catalyzes conversion of proenzymes,
including trypsinogen and inactive precursors of elastase, phospholipase A2 (PLA2), and carboxypeptidase, to active enzymes
Thus, complete inhibition of cathepsin B may prevent or become a treatment for AP
Factors that may initiate gallstone pancreatitis include reflux of bile into the PD or obstruction of the PD at the ampulla from stone(s) or from edema resulting from the passage of a stone
Reflux of bile into the PD could occur when the distal bile and PDs form a common channel and a gallstone becomes impacted in the duodenal papilla.
ARDS may be induced by active phospholipase A (lecithinase), which digests lecithin, a major component of lung surfactant
The pathogenesis of hypocalcemia is multifactorial
and includes hypoalbuminemia (the most important
cause), hypomagnesemia, calcium-soap formation, hormonal imbalances binding of calcium by free fatty acid–albumin complexes, intracellular translocation of calcium, and systemic exposure to endotoxin
Pancreatic infection (infected necrosis and infected pseudocyst) can occur from the hematogenous route or from translocation of bacteria from the colon into the lymphatics
Evidence has emerged indicating that smoking is an independent risk factor for AP
If the serum ALT level is elevated in such a patient, then gallstones as the cause may be even a stronger consideration.
Conditions That Predispose to Acute Pancreatitis
Obstruction Gallstones Tumors Parasites Duodenal diverticula Annular pancreas Choledochocele
Alcohol/other toxins/drugs Ethyl alcohol Methyl alcohol Scorpion venom Organophosphorus insecticides
Drugs
Metabolic abnormalities Hypertriglyceridemia Diabetes mellitus Hypercalcemia Infection Vascular disorders Vasculitis Emboli to pancreatic blood vessels Hypotension/ischemia Trauma
Postoperative state
Post-ERCP
Hereditary/familial/genetic Controversial Pancreas divisum SOD Miscellaneous Idiopathic
The most common obstructive process leading to pancreatitis is gallstones, which cause approximately ∼40% to 60% of cases of AP
However, only 3% to 7% of patients with gallstones develop pancreatitis.
Gallstone pancreatitis is more common in women than men because gallstones are more frequent in women.
AP occurs more frequently when stones are less than 5 mm in diameter
The triad of serum GGT ≥40 U/L, ALT ≥150 U/L, and lipase ≥15× ULN within 48 hours of presentation have been used as simple clinical predictors of acute biliary pancreatitis in children
AP is rare in pregnancy, occurring most commonly
in the third trimester, and gallstones are the most common cause
Biliary sludge is a viscous suspension in gallbladder bile that may contain small (<3 mm) stones (i.e., microlithiasis).
Because small stones can hide in biliary sludge, the 2 are commonly referred to together as biliary sludge and microlithiasis
Biliary sludge is asymptomatic in most patients. It is usually composed of cholesterol monohydrate crystals or calcium bilirubinate granules
sludge produces a mobile, low-amplitude echo that does not produce an acoustic shadow and that layers in the most dependent part of the gallbladder.
Sludge may result from functional bile stasis, such as that associated with prolonged fasting or TPN, or from mechanical stasis, such as occurs in distal bile duct
obstruction. In addition, the cephalosporin antibiotic ceftriaxone can form sludge within the biliary system when its solubility in bile is exceeded
Pancreatic tumors, presumably by obstructing the PD, infrequently cause acute and recurrent AP, especially in individuals older than age 40, and AP also increases the risk of subsequent pancreatic cancers
Pancreatitis, especially chronic pancreatitis, was associated with a significantly increased risk of PC, and the risk decreased with increasing duration since the diagnosis of pancreatitis.
The most common tumor that presents in this manner is intraductal papillary mucinous neoplasm
intraductal papillary mucinous neoplasm (both side branch and main duct)
Alcohol is the second most common cause of AP after gallstones and causes at least 30% of the cases
Cigarette smoking has been shown to be an
independent risk factor for AP
Alcohol is the most common etiology of chronic pancreatitis in developed countries.
Prolonged alcohol consumption (more than 4 to 5 drinks per day for at least 5 years) is required, and the lifetime risk of AP in such drinkers is only 2% to 5%.
The various mechanisms for chronic pancreatitis include:
- The necrosis-fibrosis sequence,
- Direct metabolic-toxic effect of alcohol on acinar cells.
- Oxidative stress due to free radicals.
- The Sentinel Acute Pancreatitis Event (SAPE) hypothesis states that most causes of chronic pancreatitis are due to a 2-hit model, where a single episode of AP causes infiltration
of inflammatory cells and activation of pancreatic stellate cells and in susceptible individuals with risk factors, further leads to fibrosis.
Drug-induced pancreatitis tends to occur within 4 to 8 weeks of beginning a drug
A recent meta-analysis of thirteen studies revealed
a marginally higher risk of AP with DPP-4 inhibitors
drug-induced pancreatitis tends to be mild and
self-limited. The diagnosis should only be entertained after alcohol, gallstones, hypertriglyceridemia, hypercalcemia, and tumors (in appropriate-aged patients) have been ruled out
Finally, there is no evidence that any medication causes chronic pancreatitis.
Hypertriglyceridemia is perhaps the third most common identifiable cause of pancreatitis, after gallstones and alcoholism, accounting for anywhere from 2% to 5%1 to 20% of cases
Serum TG concentrations above 1000 mg/dL (11
mmol/L) may precipitate attacks of AP. However, more recent studies suggest that the serum TGs may have to be even higher to precipitate AP, perhaps above 2000 mg/dL, and with obvious lactescent (milky) serum due to increased concentrations of chylomicrons
3 types of patients develop hypertriglyceridemia-induced pancreatitis.
The first is a poorly controlled diabetic patient
with a history of hypertriglyceridemia.
The second is an alcoholic patient with hypertriglyceridemia detected on hospital admission.
The third (15% to 20%) is a nondiabetic, nonalcoholic,
nonobese person who has drug- or diet-induced
hypertriglyceridemia. Drug-induced disease is more likely to occur if there is a background of hypertriglyceridemia prior to drug exposure
Diabetics are at an increased risk for developing AP
The risk may be due to the increased prevalence
of gallstones and hypertriglyceridemia in this population.
In a large study of type 2 diabetic patients
Hypercalcemia of any cause is rarely associated with AP. Proposed mechanisms include deposition of calcium salts in the PD lumen and calcium activation of trypsinogen to trypsin within the pancreatic parenchyma
Diagnosis of pancreatic trauma is highly dependent on CT, MRI, or MRCP, which may show enlargement of a portion of the gland caused by a contusion or subcapsular hematoma, pancreatic inflammatory changes, or fluid within the anterior pararenal space if there is ductal disruption.
CT may be normal during the first 2 days despite significant pancreatic trauma. If there is a strong clinical suspicion of pancreatic injury, or if the CT or MRCP scan shows an abnormality, ERCP is required to define whether there is PD injury.
If the PD is intact and there are no other significant intra-abdominal injuries, surgery is not required
AP is the most common and feared complication of ERCP, associated with substantial morbidity and occasional mortality
Asymptomatic hyperamylasemia occurs after 35%
to 70% of ERCPs.133 Clinical AP occurs in 5% of diagnostic ERCPs, 7% of therapeutic ERCPs, and up to 25% in those with suspected SOD or in those with a history of post-ERCP pancreatitis (PEP)
Factors That Increase the Risk of Post-ERCP Pancreatitis
PATIENT-RELATED
Young age, female gender, suspected SOD, history of recurrent
pancreatitis, history of post-ERCP pancreatitis, normal serum
bilirubin level
PROCEDURE-RELATED
Pancreatic duct injection, difficult cannulation, pancreatic sphincterotomy,
precut access, balloon dilation
OPERATOR OR TECHNIQUE-RELATED
Trainee (fellow) participation, nonuse of a guidewire for cannulation, failure to use a pancreatic duct stent in a high-risk procedure
In general, the more likely a patient is to have an abnormal bile duct or PD, the less likely the patient will develop PEP
The patient most at risk of developing PEP was a woman with suspected choledocholithiasis and normal serum bilirubin, who underwent a sphincterotomy and no stone was found
the 2-hour serum amylase and lipase
were more accurate than a clinical assessment in distinguishing nonpancreatitis abdominal pain from post-ERCP AP.
Serum amylase values above 276 IU/L (reference range, 30 to 70 IU/L) and lipase above 1000 IU/L (reference range, 45 to 110 IU/L) 2 hours after completing the procedure had almost a 100% positive predictive value (PPV) for PEP.
if the serum amylase was normal after 3 hours,
only 1% of patients developed PEP, compared with 39% if the amylase was greater than 5 times the upper limit of normal
A number of drugs have not shown any benefit including nitroglycerin, nifedipine, sprayed lidocaine, and injected botulinum toxin. The protease inhibitor gabexate showed some benefit in small trials but is very expensive.
Inhibiting exocrine pancreatic secretion by somatostatin was not beneficial in many studies, and its analog octreotide reduces only hyperamylasemia.
The 3 major modalities shown to reduce the risk are post- ERCP pancreatitis include prophylactic pancreatic stents, preprocedural intravenous fluids, and rectal administration of NSAIDs. Pancreatic stent placement clearly decreases the risk of PEP in high-risk patients
Prophylactic PD stents are either a 3 French
or 5 French and can be less than 5 cm or greater than 5 cm in length and placed temporarily to cover the 2- to 3-day period of ampullary edema.
More than 70% of the stents spontaneously fell out within 3 to 4 days after providing an access for the bile and pancreatic juice during the period of ampullary edema and
swelling.
If a radiograph after a week suggests the stent has not
migrated, it needs to be removed endoscopically, usually before 14 days.
Diameter of >5 Fr and a length of >5 cm seems
to have a better protective effect against post-ERCP pancreatitis, compared with shorter and thinner stents
Postoperative pancreatitis can occur after thoracic or abdominal surgery.
Pancreatitis occurs after 0.4% to 7.6% of cardiopulmonary bypass operations
AP has been rarely associated with Crohn disease.160 A recent case-control study from Denmark found a 4-fold increase in AP in patients with Crohn’s and a 1.5-fold increase in patients with UC.
This increase has been attributed by some to the use
of drugs such as 5-aminosalicylates/sulfasalazine and thiopurines (azathioprine/6-mercaptopurine
Pancreas divisum is the most common congenital malformation of the pancreas, occurring in 5% to 10% of the general healthy population
Recurrent AP report that SOD (usually defined as a
basal pancreatic sphincter pressure >40 mm Hg) is the most common abnormality discovered, occurring in approximately 35% to 40% of patients.
The main argument in favor of this entity as
a cause of AP is the many observational series that report that endoscopic pancreatic sphincterotomy or surgical sphincteroplasty reduces recurrent attacks of pancreatitis
For patients with type 3 SOD,
the results of a large rigorously conducted multicenter RCT, the EPISOD trial, has been published.
The trial concluded that in patients with abdominal pain after cholecystectomy undergoing ERCP with manometry, sphincterotomy versus sham sphincterotomy did not reduce disability due to pain. These findings do not support ERCP and sphincterotomy for these patients
Pain in the lower abdomen may arise from the
rapid spread of pancreatic exudation to the left colon.
Onset of pain is rapid but not as abrupt as that of a perforated viscus. Usually it is at maximal intensity in 10 to 20 minutes.
Occasionally, pain gradually increases and takes several hours to reach maximum intensity. Pain is steady and moderate to very severe. There is little pain relief with changing position
Frequently, pain is unbearable, steady, and boring. Band-like radiation of the pain to the back occurs in half of patients.
Pain that lasts only a few hours and then disappears suggests a disease other than pancreatitis, such as biliary pain or peptic ulcer.
Pain is absent in 5% to 10% of attacks, and a painless presentation may be a feature of serious fatal disease
Ninety percent of affected patients have nausea and vomiting.
Vomiting may be severe, may last for hours, may be accompanied by retching, and may not alleviate pain. Vomiting may be related to severe pain or to inflammation involving the posterior gastric wall
Guarding is more marked in the upper abdomen. Tenderness and guarding can be less than expected,
considering the intensity of discomfort.
Abdominal rigidity, as occurs in diffuse peritonitis, is unusual but can be present, and differentiation from a perforated viscus may be impossible in these instances. Bowel sounds are reduced and may be absent
Ecchymosis in 1 of both flanks (Gray Turner sign or about the periumbilical area (Cullen sign, owing to extravasation of hemorrhagic exudate to these areas.
These signs occur in less than 1% of cases and are associated with a poor prognosis
Rarely there is a brawny erythema of the flanks caused by extravasation of pancreatic exudate to the abdominal wall.
A palpable epigastric mass may appear during the disease from a pseudocyst or a large inflammatory mass.
Initially the temperature may be normal, but within 1 to 3 days it may increase to 101°F to 103°F, owing to the severe retroperitoneal inflammatory process and the release of inflammatory mediators from the pancreas
panniculitis with subcutaneous
nodular fat necrosis that may be accompanied by polyarthritis (PPP syndrome
Subcutaneous fat necroses are 0.5- to 2-cm tender red nodules that usually appear over the distal extremities but may occur over the scalp, trunk, or buttocks.
They occasionally precede abdominal pain or occur
without abdominal pain, but usually they appear during a clinical episode and disappear with clinical improvement
Hepatomegaly, spider angiomas, and thickening of palmar sheaths favor alcoholic pancreatitis.
Eruptive xanthomas and lipemia retinalis suggest hyperlipidemic pancreatitis.
Parotid pain and swelling are features of mumps. Band keratopathy (an infiltration on the lateral margin of the cornea) occurs with hypercalcemia.
Microembolization in the retina can lead to typical fundus findings associated with visual disturbances including blindness
The abdominal pain of biliary pain may simulate AP. It is frequently severe and epigastric, but it typically lasts for several hours rather than several days
The pain of a perforated peptic ulcer is sudden, becomes diffuse, and precipitates a rigid abdomen; movement aggravates pain.
Nausea and vomiting occur but disappear soon after onset of pain
In mesenteric ischemia or infarction, the clinical setting often is an older person with atrial fibrillation or atherosclerotic disease who develops sudden pain out of proportion to physical findings, bloody diarrhea, nausea, and vomiting.
Abdominal tenderness may be mild to moderate, and muscular rigidity may not be severe despite severe pain.
In intestinal obstruction, pain is cyclical, abdominal distention is prominent, vomiting persists and may become feculent, and peristalsis is hyperactive and
often audible
diagnosis of AP relies on at least a 3-fold elevation
of serum amylase or lipase in the blood
In healthy persons, the pancreas accounts for 40% to 45% of serum amylase activity, the salivary glands accounting for the rest
P) isoamylase, measurement of P-isoamylase can improve diagnostic accuracy. However, this test is rarely used
The total serum amylase test is most frequently ordered to diagnose AP, because it can be measured quickly and cheaply.
It rises within 6 to 12 hours of onset and is cleared fairly rapidly from the blood (half-life, 10 hours).
The serum amylase is usually increased on the first day of symptoms, and it remains elevated for 3 to 5 days in uncomplicated attacks.
Sensitivity is at least 85%.
The serum amylase may be normal or only minimally elevated in fatal pancreatitis,6 during a mild attack or an attack superimposed on chronic pancreatitis (because the pancreas has little remaining acinar tissue), or during recovery from AP as amylase is cleared from the circulation.
In AP, the serum amylase concentration is
usually more than 2 to 3 times the upper limit of normal; it is usually less than this with other causes of hyperamylasemia
salivary glands, fallopian tubes
Furthermore, mass lesions such as papillary cystadenocarcinoma of the ovary, benign ovarian cyst,
and carcinoma of the lung can cause hyperamylasemia because they produce and secrete salivary (S-type) isoamylase.
Leakage of P-type isoamylase across the intestine with peritoneal amylase absorption probably explains hyperamylasemia in patients with intestinal infarction or GI tract perforation.
Renal failure can increase serum amylase up to 4 to 5 times the upper limit of normal because of decreased renal clearance of this enzyme
The sensitivity of serum lipase for the diagnosis of AP is similar to that of serum amylase and is at least 85%
Lipase may have greater specificity for pancreatitis than amylase, however. Serum lipase is normal when serum amylase is elevated in nonpancreatic conditions such as salivary gland disease, amylase-producingtumors, gynecologic conditions such as salpingitis, and macroamylasemia.
Serum lipase always is elevated on the first day of
illness and remains elevated longer than does the serum amylase,providing a slightly higher sensitivity
Combining amylase and lipase does not improve diagnostic accuracy and increases cost
In the absence of pancreatitis, serum lipase may increase less than 2-fold above normal in renal insufficiency.
With acute GI conditions that resemble AP serum lipase increases to levels less than 3-fold above normal,presumably by absorption through an ischemic, inflamed, or perforated intestine.
Rarely, a nonpancreatic abdominal condition
such as small bowel obstruction can raise the serum lipase (and amylase) above 3 times normal
The most common primary diagnoses in non-AP patients with elevated lipase included shock, cardiac arrest and malignancy
Elevated serum lipase level can have non-pancreatic origins, with liver and renal failure being the most frequent.
Lipase should replace amylase as the first-line laboratory investigation for suspected AP
Serum lipase levels of more than 2.5 times the upper limit of normal prior to refeeding is a potentially useful threshold to identify patients at high risk of developing oral feeding intolerance
The WBC count frequently is elevated, often markedly so in severe pancreatitis, and does not generally indicate infection.
The blood glucose also may be high and associated with high levels of serum glucagon. Serum AST, ALT, alkaline phosphatase, and bilirubin also may increase, particularly in gallstone pancreatitis.
Decreased serum calcium is not from saponification. The erythrocyte mean corpuscular volume has been shown to help differentiate alcoholic from nonalcoholic AP
Alcoholic patients tend to have a higher mean corpuscular volume due to the toxic effects of alcohol on erythrocyte formation in the bone marrow.
Serum TG levels increase in AP but also with alcohol use, uncontrolled diabetes mellitus, or defective TG metabolism
localized ileus of a segment of small intestine (“sentinel loop”) or the colon cutoff sign in more severe disease
Small intestinal abnormalities are due to inflammation in proximity to small bowel mesentery and include ileus of 1 or more loops of jejunum (the sentinel loop), of the distal ileum or cecum, or of the duodenum. Generalized ileus may occur in severe disease.
spread of exudate to specific areas of the colon may produce spasm of that part of the colon and either no air distal to the spasm (the colon cutoff sign) or dilated colon proximal to the spasm.
Head-predominant pancreatitis predisposes to spread of exudate to the proximal transverse colon,
producing colonic spasm and a dilated ascending colon.
Uniform pancreatic inflammation predisposes spread of exudate to the inferior border of the transverse colon and an irregular haustral pattern
Exudate from the pancreatic tail to the phrenicocolic ligament adjacent to the descending colon may cause spasm of the descending colon and a dilated transverse colon.
Other findings on plain radiography of the abdomen may give clues to etiology or severity, including calcified gallstones (gallstone pancreatitis),
pancreatic stones or calcification (acute exacerbation of chronic pancreatitis), and ascites (severe pancreatitis).
Gas in the retroperitoneum may suggest a pancreatic abscess
Abnormalities visible on the chest roentgenogram occur in 30% of patients with AP, including elevation of a hemidiaphragm, pleural effusion(s), basal or plate-like atelectasis secondary to limited respiratory excursion, and pulmonary infiltrates.
Pleural effusions may be bilateral or confined to the left side; rarely they are only on the right side
Patients with AP found to have a pleural effusion and/or pulmonary infiltrate on admission are more likely to have severe disease
During the first 7 to 10 days, there also may be signs of ARDS or heart failure
Abdominal US is used during the first 24 hours of hospitalization to search for gallstones, dilation of the bile duct due to choledocholithiasis, and ascites
Ascites is common in patients with moderate to severe AP as protein-rich fluid extravasates from the
intravascular compartment to the peritoneal cavity
If the pancreas is visualized by US (bowel gas obscures the pancreas 25% to 35% of the time), it is usually diffusely enlarged and hypoechoic
During the course of AP, US can be used to evaluate progression of a pseudocyst
Owing to overlying gas, the diagnosis of cholelithiasis may be obscured during the acute attack but may be found after bowel gas has receded.
EUS is useful at an early stage in AP to
detect common bile duct stones and allow proceeding to ERCP at the same time, thus avoiding ERCP if the bile duct is clear of stones.
EUS can also predict severity of AP by alterations in the echo texture of the pancreas
EUS done at admission can reliably detect pancreatic necrosis and co-existent disorders like CBD stones209 and predict mortality.
obtaining EUS after a period of 8 to 12 weeks to look for causes like microlithiasis in the common bile duct, small tumors near the PD causing obstruction, chronic pancreatitis presenting as an AP attack, and some anatomical abnormalities missed on CT scan
CT is the most important imaging test for the diagnosis of AP and its intra-abdominal complications.
The 3 main indications for a CT in AP are to
(1) exclude other serious intra-abdominal conditions
(e. g., mesenteric infarction or a perforated peptic ulcer)
(2) stage the severity of AP
(3) determine whether complications of pancreatitis are present (e.g., involvement of the GI tract or nearby blood vessels and organs, including liver, spleen, and kidney)
Pancreatic necrosis manifested as perfusion defects after IV contrast may not appear until 48 to 72 hours after onset of AP
Although the presence of gas in the pancreas suggests pancreatic infection with a gas-forming organism, this finding can also accompany sterile necrosis with microperforation of the gut or an adjacent pseudocyst into the pancreas
MRI is superior to CT in assessing
fluid collections by showing the necrotic debris better
MRI is better than CT, but equal to EUS and ERCP in detecting choledocholithiasis
MRI also has the advantage over CT in better delineating the PD and showing lesions like PD disruption or disconnection and stones in the PD
The use of IV secretin prior to MRCP allows
a better visualization of the PDs
Alcoholic pancreatitis occurs more frequently in men approximately 40 years old.
The first clinical episode usually occurs after 5 to 10 years of heavy alcohol consumption.
By contrast, biliary pancreatitis is more frequent in
women, and the first clinical episode is often after the age of 40 years. Recurrent attacks of AP suggest an alcohol etiology, but unrecognized gallstones may cause recurrent pancreatitis
Among patients with acute biliary pancreatitis discharged from the hospital without cholecystectomy, 30% to 50% develop recurrent
AP relatively soon after discharge (average time to recurrent pancreatitis, 108 days)
Thus removing the gallbladder in biliary pancreatitis is imperative
The specificity for gallstone pancreatitis of a serum ALT
concentration greater than 150 IU/L (≈3-fold elevation) is 96%; the PPV is 95%, but the sensitivity is only 48%.205
The serum AST concentration is nearly as useful as the ALT, but the total bilirubin and alkaline phosphatase concentrations are not as helpful to distinguish gallstone pancreatitis from alcoholic and other etiologies
Conventional abdominal US should be performed in every patient with a first attack of AP to search for gallstones
MRCP is as accurate, but because of its noninvasive approach, it is preferred if a clinician has a lower suspicion that a common duct stone may be present
Predicting the severity is very important during the first 24 to 72 hours, mostly at admission and during the first 24 hours.
predictors of persistent organ failure (severe AP) and infected pancreatic necrosis observed that it is justifiable to use the blood urea nitrogen (BUN) level for prediction of persistent organ failure after 48 hours of admission and
procalcitonin for prediction of infected pancreatic necrosis in patients with confirmed pancreatic necrosis
Recent guidelines and reviews recommended the following predictors at admission to be useful while considered together with clinical judgement:
advanced age (>60 years), BMI, Charlson’s comorbidity index, pleural effusions or infiltrates on the admission chest radiograph, elevated hematocrit elevated BUN level elevated serum creatinine level CRP >15 mg/dL at 48 hours.
The height of elevation of the serum amylase and lipase does not correlate with severity
When AP is superimposed on chronic pancreatitis, it is usually less severe than AP without chronic pancreatitis. When superimposed on chronic
pancreatitis, weight loss, advanced age, and comorbidities predict severity in a population-based study
Radial EUS in acute biliary pancreatitis showed a significant relationship between the severity of AP with diffuse parenchymal edema, periparenchymal plastering, and/or diffuse retroperitoneal free fluid accumulation, and peri-pancreatic edema, and also predicted mortality
presence of SIRS at admission and persistence of SIRS at 48 hours increases the morbidity and mortality rate
APACHE II has been the most validated system for many years and none of the later scoring systems later reported proved to be superior in any consistent manner
Ranson and colleagues identified 11 signs that had prognostic significance during the first 48 hours
score of 3 or more is considered to indicate severe AP
BISAP (Bedside Index for Severity in AP), assigns
each parameter 1 point:
BUN greater than 25 mg/dL Impaired mental status, SIRS, Age older than 60 years, and Pleural effusion, for a possible total of 5 points.
A BISAP score of 4 or 5 is associated with a 7- to 12-fold increased risk of developing organ failure.
BISAP is not superior to APACHE II.
SIRS is defined by 2 or more of the following 4 criteria:
Pulse >90 beats/minute
rectal temperature <36°C or >38°C
WBC count <4000/mm3 or >12,000/mm3, and
a respiratory rate greater than 20/minute or an arterial PCO2 <32 mm Hg
Balthazar
A Normal pancreas consistent with mild
pancreatitis 0 points
B Focal or diffuse enlargement of the gland,
including contour irregularities and
inhomogeneous attenuation but without
peripancreatic inflammation 1 point
C Grade B plus peripancreatic inflammation 2points
D Grade C plus associated single fluid collection 3 points
E Grade C plus 2 or more peripancreatic fluid
collections or gas in the pancreas or
retroperitoneum 4 points
CTSI=Balthazar Grade Points Plus Necrosis Score*
Necrosis Score Points
Absence of necrosis 0 Points
Necrosis of up to 33% of the pancreas 2 Points
Necrosis of 33%-50% 4 Points
Necrosis of >50% 6 Points
*Highest attainable CTSI score: 4 (Balthazar grade E) + 6 (necrosis of >50%) = 10 points.
The CT grading scores correlate better
with local complications (pseudocysts and abscesses) than with mortality.
A pleural effusion documented within 72 hours of admission by chest radiography (or CT) correlates with severe disease.
Early course: 0-72 hr Is there organ failure?
No Admission to medical/surgical floor NPO, IV hydration (250-400 cc/hr) Nasal oxygen Frequent evaluation of oxygen saturation Hematocrit daily/BUN twice daily for 48 hours Serum electrolytes daily Pain control
Yes Admission to an ICU Same orders as for floor admission Central line placement Evaluate need for assisted ventilation Assess for bile duct obstruction If bilirubin rising, consider urgent ERCP
Later course: >72 hours Evidence of severe disease or organ failure?
No Early refeeding Evaluate for etiology If gallstones, early cholecystectomy If alcohol, address psychosocial issues If high serum TG, medical therapy
Yes
To ICU if patient not already there
Observe for biliary sepsis; if present, consider emergency ERCP Enteral feedings (NJ or NG) CT to evaluate for necrosis
Interstitial pancreatitis on CT without peripancreatic necrosis:
Continue supportive care
Observation
Pancreatic/peripancreatic necrosis on CT:
Continue supportive care
Enteral feedings
If infection suspected, consider antibiotics
Late course: 7-28 days Patient improving?
Yes
Consider oral refeeding
No
If on antibiotics, consider FNA of pancreas for culture and change of antibiotics
If not on antibiotics and FNA negative, keep off antibiotics
Beyond 28 days Patient improving?
Consider refeeding If patient cannot tolerate feedings, consider necrosectomy
Consider necrosectomy by endoscopic, radiologic, or surgical means
NG intubation is not used routinely because it is not beneficial in mild pancreatitis.
It is used only to treat gastric or intestinal ileus or intractable nausea and vomiting.
Similarly, routine use of PPIs or H2RAs have not been shown to be beneficial.
hypotension (systolic blood pressure less than 110 mm Hg despite IV volume administration), pulmonary failure (oxygen saturations less than 90% despite maximally possible oxygen replacement therapy by nasal cannula or face mask), or renal insufficiency (serum creatinine greater than 2 mg/dL despite maximal intravenous volume administration
Thus an admission hematocrit of more than 44%
and a failure of the admission hematocrit to decrease at 24 hours have been shown to be predictors of necrotizing pancreatitis
an elevation and/or rising BUN is associated with increased mortality
decrease in SIRS score as well as CRP levels
The addition of hydroxyethyl starch to usual intravenous fluids does not reduce the risk of mortality, and may increase the risk of persistent multiple organ system failure in AP
fluid rate of 5 to 10 mL per kilogram body weight per hour or 250 to 500 mL per hour of probably lactated Ringer solution, preferably during
the first 24 hours after admission
ARDS is associated with severe dyspnea, progressive hypoxemia, and increased mortality.
It generally occurs between the second and seventh day of illness (but can be present on admission) and consists of increased alveolar capillary permeability causing interstitial edema.
Chest radiography may show multilobar alveolar
infiltrates. Treatment is endotracheal intubation with positive end-expiratory pressure ventilation, often with low tidal volumes to protect the lungs from volutrauma.
maintain oxygen saturations well over 90%.
An increase in cardiac index and a decrease in total peripheral resistance may be present and respond to infusion of crystalloids. If hypotension persists even with appropriate fluid resuscitation, intravenous vasopressors may be required.
Hyperglycemia may present during the first several days of severe pancreatitis but usually disappears as the inflammatory process subsides.
Blood sugars fluctuate, and insulin should be administered cautiously. Leptin levels were associated with persistent hyperglycemia early in the course of AP
Hypocalcemia is mainly due to a low serum albumin.
Serum albumin is lost as albumin-rich intravascular fluid extravasates into peritoneum and retroperitoneum, as well as the negative phase reactant effect on reducing albumin synthesis during the acute illness phase.
This albumin loss causes a decrease in the calcium normally bound to the albumin. Because this loss is nonionized, hypocalcemia is largely asymptomatic and requires no specific therapy.
Imipenem, fluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin), and metronidazole emerged as the drugs that achieved the highest inhibitory concentrations in pancreatic tissue,
ERCP in a patient with biliary pancreatitis can be urgent or elective before cholecystectomy.
Urgent ERCP has been variously defined as within 24 hours, 48 hours, or 72 hours.
For mild biliary AP, same-admission laparoscopic
cholecystectomy is the standard therapy, and before such procedure an elective ERCP or intraoperative cholangiography are the choices.
The most recent guidelines recommended urgent
ERCP within 72 hours for cholangitis and possibly for persistent biliary obstruction defined by elevated liver tests and/or the presence of a stone in the common bile duct on imaging
urgent ERCP within 24 to 48 hours is indicated if the patient has cholangitis, total serum bilirubin >5 mg/dL, clinical deterioration (worsening pain and white cell count and worsening vital signs), or a stone documented in the common bile duct on imaging.
AGA technical review reported a meta-analysis
on 8 RCTs of urgent ERCP in acute biliary pancreatitis, comprising 935 patients.
This report found no benefit of urgent ERCP in acute biliary pancreatitis with regard to single organ failure or multiple organ failure, infected peripancreatic necrosis, occurrence of necrotizing pancreatitis, or mortality
urgent ERCP in acute biliary pancreatitis is probably in
those patients with cholangitis
If the serum lipase level was more
than 3-fold elevated, clinical relapse rate with refeeding was 39%, compared with 16% in those with a lipase <3-fold elevated.
Another meta-analysis reported that serum lipase levels of 2.5 fold or higher are associated with oral feeding intolerance
Based on 11 RCTs, an AGA technical review and AGA guidelines recommended early feeding (usually within 24 hours) for all patients with AP (mild, moderately severe, and severe) as tolerated by the patient. However, if there is significant nausea and
vomiting or ileus, then one may have to wait until they subside.
increased harm with TPN compared with enteral or oral feeding with regard to single and multiple organ failure and infected necrosis,
AGA guidelines gave a strong recommendation based
on moderate quality of evidence, which in AP enteral nutrition is preferred to TPN if the patient is not able to tolerate oral feeding for prolonged period
Thus a diagnosis of moderately severe or severe AP usually takes 3 to 5 days to firmly establish, and at that time if oral feeding is not possible, nasogastric or nasojejunal feeding may be considered
For those patients who can do not tolerate anything by mouth due to vomiting and/or worsening pain after 3 to 5 days, a low-fat diet given by nasogastric tube and, if not tolerated, a postpyloric feeding should be given. One should rarely require TPN
These include urgent (24 to 72 hours) ERCP, elective ERCP before cholecystectomy for gallstones, and cholecystectomy as the definitive treatment.
The recurrence of further attacks of AP is 18% in 6 weeks if cholecystectomy is not performed at the time of index attack of biliary pancreatitis
more recent guidelines recommend same-admission cholecystectomy for cases of mild and interstitial pancreatitis
The recommendations varied from after the inflammation subsides, and all the fluid collections
stabilize to 6 weeks after the attack.
A recent RCT where cholecystectomy was performed within 72 hours of randomization in patients with acute biliary pancreatitis compared with cholecystectomy performed after 25 to 30 days demonstrates
a significantly reduced number of pancreaticobiliary complications and readmissions with early surgery but no difference in mortality
If the patient is diagnosed as having interstitial acute biliary pancreatitis and is being evaluated for same admission cholecystectomy, and if the white count is elevated before such cholecystectomy, a repeat CT scan should be performed in order to detect necrotizing pancreatitis that had not manifested on the initial CT scan.
After the initial phase of 2 weeks, pancreatic fluid collections appear to become more demarcated and develop a wall, usually by 4 weeks.
As acute (peri-)pancreatic fluid collections usually have resolved by that time, those that persist and have a wall usually represent WON rather than pseudocysts
Approximately two thirds of patients with necrotizing
pancreatitis resolve without any interventions
operating early (within 2 weeks) increases mortality and morbidity and subsequent recommendations
emphasized operating later in the course after the fluid
collections develop a wall, which is usually around 4 weeks
Complications of Acute Pancreatitis
LOCAL Pseudocyst Sterile necrosis (peripancreatic, pancreatic, or both) Infected necrosis (peripancreatic, pancreatic, or both) Abscess GI bleeding Pancreatitis-related Splenic artery rupture or splenic artery pseudoaneurysm rupture Splenic vein rupture Portal vein rupture Splenic vein thrombosis leading to gastroesophageal variceal bleeding Pseudocyst or abscess hemorrhage Post-necrosectomy bleeding Nonpancreatitis-related Mallory-Weiss tear Alcoholic gastropathy Stress-related mucosal gastropathy Splenic complications Infarction Rupture Hematoma Splenic vein thrombosis Fistulization to or obstruction of the small intestine or colon Hydronephrosis
SYSTEMIC Respiratory failure Renal failure Shock Hyperglycemia Hypocalcemia DIC Fat necrosis (subcutaneous nodules) Retinopathy Psychosis
Disconnected PD syndrome is an entity when a significant amount of pancreatic body necrosis disconnects the PD in the proximal and distal segments.
The diagnosis is made usually by necrosis of the middle part of the pancreas initially, a persistent fluid collection in the area of necrosis, complete cutoff of the PD on ERCP in the same region, and a viable enhancing distal segment of the pancreas.
Although a self-expanding metal stent can be used
for short duration of 3 weeks, subsequent treatment would be pigtail catheters either from a single entrance from the stomach into the fluid collection or multiple gait ways for better egress of pancreatic secretions
Splanchnic venous thrombosis occurs in 1.8% of patients with Anticoagulation is safe in patients
without bleeding complications
Use of anticoagulation is recommended for a period of 3 to 6 months if there are no underlying hypercoagulable conditions
15% of patients with AP developed new onset diabetes mellitus within 12 month period after the acute event and a >2-fold risk at 5 years
exocrine insufficiency occurs in 40% of individuals with newly diagnosed prediabetes or diabetes mellitus after AP
Abdominal compartment syndrome (ACS) is defined as a sustained intra-abdominal pressure greater than 20 mm Hg (typically determined by a pressure-recording catheter in the urinary bladder) that is associated with the development of organ dysfunction or failure
Pancreatic encephalopathy consists of a variety of central nervous system symptoms occurring in patients with AP, including agitation, hallucinations, confusion, disorientation, and coma.
Purtsher retinopathy (discrete flame-shaped hemorrhages with cotton wool spots) can cause sudden blindness
It is thought to be due to microembolization in the choroidal and retinal arteries.
Chronic inflammation, fibrosis, and eventual
destruction of ductal, exocrine (acinar cell), and endocrine (islets of Langerhans) tissue characterize the histology of chronic pancreatitis, producing varying degrees of symptoms and structural and functional derangements of the gland.
Chronic pancreatitis may also be defined based on clinical features (abdominal pain, exocrine insufficiency [steatorrhea], or endocrine insufficiency [diabetes mellitus]) or on imaging techniques including US, CT, EUS, MRI, MRCP, and ERCP.
Similarly, aging, smoking, chronic kidney disease, and
long-standing diabetes mellitus can induce histologic changes within the pancreas that are difficult to distinguish from those of chronic pancreatitis
Chronic pancreatitis is more common in men and is most commonly a disease of middle age, with most patients diagnosed above the age of 40
Overall, 10-year survival in patients with chronic pancreatitis is about 70%, and 20-year survival about 45%
In early chronic pancreatitis the damage is
varying and uneven. Areas of interlobular fibrosis are seen, with the fibrosis often extending to the ductal structures.
Infiltration of the fibrotic area and lobules with lymphocytes, plasma cells, mast cells, and macrophages is seen
The ducts may contain eosinophilic protein plugs. In affected lobules, acinar cells are surrounded and replaced by fibrosis.
The islets are usually less severely damaged until very late in the course of the disease
Features of acute pancreatitis also may be seen, such as edema, acute inflammation, and acinar cell or fat necrosis.
As the disease progresses, fibrosis within the lobules and between lobules becomes more widespread.
The pancreatic ducts become more abnormal with progressive fibrosis, stricture formation, and dilation.
The ductal protein plugs may calcify and obstruct major pancreatic ducts. Ductal epithelium may become cuboidal, may develop atrophy or squamous metaplasia, or may be replaced by fibrosis entirely.
Activated pancreatic stellate cells may be identified
in close association with fibrosis
Many of these changes, in particular perilobular fibrosis and ductal metaplasia, are also commonly seen in patients of advanced age without chronic pancreatitis, and in patients with long-standing diabetes mellitus
Obstructive chronic pancreatitis (associated with obstruction of the main pancreatic duct by a tumor or stricture) can differ slightly, in that the histologic changes are limited to the gland upstream of the
obstruction and protein precipitates and intraductal stones are not usually seen.
(Type 1) a more robust lymphoplasmacytic infiltrate, including plasma cells, is seen and these are usually positive when stained for immunoglobulin G
subtype 4 (IgG4). Obstructive phlebitis affecting the major and minor veins and a whorled (storiform) fibrosis pattern are also
characteristic, a pattern termed lymphoplasmacytic sclerosing
pancreatitis.
Type 1 autoimmune pancreatitis (AIP) is considered
a manifestation of IgG4-related disease
second pattern (Type 2) termed idiopathic duct-centric chronic pancreatitis is characterized by neutrophilic infiltration and the absence of IgG4 positive plasma cells
loss of parenchymal cells, self-sustaining chronic inflammation, and fibrosis.
Any proposed mechanism must therefore include explanations for cellular necrosis or apoptosis, initiation and maintenance of inflammatory cell activation, and fibrogenesis by pancreatic stellate cells.
less than 5% of heavy alcohol users develop chronic pancreatitis.
The interaction of smoking and alcohol exposure is an increasingly recognized risk factor for chronic pancreatitis
hypothesis focuses on the concept that ductal obstruction (from strictures or stones
toxic-metabolic hypothesis, focuses primarily on the
role of alcohol and its metabolites (or smoking or other toxins)
necrosis-fibrosis hypothesis, which holds that the occurrence of repeated or severe episodes of acute pancreatitis with cellular necrosis or apoptosis eventually leads to the development of chronic pancreatitis as the healing process replaces necrotic tissue with fibrosis
Tobacco use is one very important cofactor for the development of alcoholic chronic pancreatitis
In Western countries, alcohol is the cause of at least 50% of all cases of chronic pancreatitis.
In nearly all patients with alcoholic chronic pancreatitis, at least 5 years (and in most patients more than 10 years) of intake exceeding 4 to 5 drinks
per day are required before the development of chronic pancreatitis.
Men are more likely than women to develop alcoholic chronic pancreatitis, possibly due to increased alcohol usage or perhaps to other genetic factors
Only 2% to 5% of heavy drinkers ultimately develop chronic pancreatitis, suggesting important cofactors
Many patients with chronic pancreatitis due to alcohol have an early phase of recurrent attacks of acute pancreatitis, which may last 5 or 6 years, followed by the later development of chronic pain or exocrine or endocrine insufficiency
Up to 40% of patients presenting with acute alcoholic pancreatitis, however, do not progress to clinically identifiable chronic pancreatitis (calcification and exocrine or endocrine insufficiency) even with very long follow-up, and may not even have recurrent attacks
Binge drinking does not appear to be associated with these acute episodes, although some studies suggest an attack may occur shortly after stopping drinking
The risk is more than 3-fold for smokers of more
than one pack per day
Smoking may account for up to 25% of the attributable risk for chronic pancreatitis, and is particularly injurious in those who also drink
There is strong evidence that smoking is an independent risk factor for chronic pancreatitis
Type 1 AIP
Lymphoplasmacytic infiltration
Dense periductal infiltrate without damage to ductal
epithelium
Storiform fibrosis
Obliterative phlebitis
Abundant (>10 cells/HPF) IgG4-positive cells
Fibroinflammatory process may extend to peripancreatic region
60-70 years
Obstructive jaundice (75%) Acute pancreatitis (15%)
Diffuse pancreatic enlargement (40%)
Focal pancreatic enlargement (60%)
IgG4 Elevated in serum (≈2⁄3 of patients)
Positive in staining of involved tissues
Biliary strictures Sialoadenitis Retroperitoneal fibrosis Pseudotumors Kidney Lung Others
Frequent relapses
Type 2 AIP
Type 2 AIP is more common in western countries but even here is less common than Type 1, accounting for less than 20% of all cases of AIP
Lymphoplasmacytic and neutrophilic infiltration
around ducts
Destruction of duct epithelium by neutrophils
(granulocytic epithelial lesion)
Obliterative phlebitis rare
No IgG4-positive cells
40-50, but may present in young adults and even
children
Obstructive jaundice (50%) Acute pancreatitis (33%)
Diffuse pancreatic enlargement (15%)
Focal pancreatic enlargement (85%)
Not associated
IBD
Rare or no relapse
Type 1 AIP is seen more commonly in men (2:1) and usually manifests in middle age or beyond.39,103 More than 85% of patients present after the age of 50 years and the mean age of presentation is 70.
Type 2 AIP presents at a younger age and may
even present in young adults and children. The most common initial presentation for both forms of AIP is painless obstructive jaundice due to obstruction of the intrapancreatic bile duct
The radiographic features of the pancreas are similar for Type 1 and Type 2 AIP. Abdominal US usually shows a diffusely enlarged and hypoechoic pancreas.
The appearance on EUS is similar.
CT most commonly reveals a diffusely enlarged sausageshaped pancreas in which enhancement with the intravenous contrast agent is delayed and prolonged
One of the hallmarks of both types of AIP is diffuse or segmental irregularity and narrowing of the pancreatic duct
The duct may be diffusely narrowed and thread-like, or may instead demonstrate alternating areas of stricture and normal caliber or dilated duct
`Type 1 AIP can be diagnosed with reasonable accuracy without a pancreatic biopsy, the diagnosis of
Type 2 AIP almost always requires pancreatic biopsy or resection
There are no clear recommendations for glucocorticoid
dose, although 0.6 to 1 mg/kg has been suggested
A common starting dose is 40 mg of prednisone daily.
International Consensus Diagnostic Criteria for Type 1 Autoimmune Pancreatitis
Typical imaging:
Diffuse enlargement of pancreas with delayed enhancement
With or without rim-like enhancement or pancreas
Long (>1⁄3 of the length of pancreatic duct) stricture, or
Multiple strictures without upstream dilation of pancreatic duct
