Internal Medicine

Acute and Chronic Pancreatitis EXIMIUS

Dr. Subia December 2019 2021

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LONG ACTING FA duodenal and
ESSENTIAL AA proximal jejunal CCK
GASTRIC ACID mucosa

Enzyme enriched Acinar cells

secretion (pancreas)

Mediated by: Parasympathetic NS (vagus nerve)

WATER AND ELECTROLYTE SECRETION

Bicarbonate
 is the ion of primary physiologic importance within pancreatic
secretion.
 The ductal cells secrete bicarbonate predominantly derived
PANCREAS from plasma (93%) more than from intracellular metabolism
- The pancreas secretes 1500–3000 mL of isosmotic alkaline (pH (7%).
>8) fluid per day containing about 20 enzymes.  enters the duct lumen through the sodium bicarbonate
- The pancreatic secretions provide the enzymes and cotransporter with depolarization caused by chloride efflux
bicarbonate needed to affect the major digestive activity of the through the cystic fibrosis transmembrane conductance
gastrointestinal tract and provide an optimal pH for the regulator (CFTR).
function of these enzymes.
ENZYME SECRETION
AMYLOLYTIC ENZYMES
 Amylase hydrolyze starch to oligosaccharides and to the
disaccharide maltose.

LYPOLYITIC ENZYMES
 Lipase
 phospholipase A2
 cholesterol esterase

PROTEOLYTIC ENZYMES
 endopeptidases (trypsin, chymotrypsin), which act on internal
peptide bonds of proteins and polypeptides
 exopeptidases (carboxypeptidases, aminopeptidases), which
act on the free carboxyl- and amino-terminal ends of peptides,
respectively
REGULATION OF PANCREATIC SECRETION  elastase.

ENTEROKINASE
 an enzyme found in the duodenal mucosa, cleaves the lysine-
Duodenal isoleucine bond of trypsinogen to form trypsin
GASTRIC ACID mucosa (S Secretin
cells) AUTOPROTECTION OF THE PANCREAS
1. the packaging of pancreatic proteases in precursor (proenzyme)
form
2. intracellular calcium homeostasis (low intracellular calcium in
the cytosol of the acinar cell promotes the destruction of
spontaneously activated trypsin)
Water and Pancreatic 3. acid-base balance
Electrolytes duct cells 4. the synthesis of protective protease inhibitors (pancreatic
secretory trypsin inhibitor [PSTI] or SPINK1), which can bind and
inactivate about 20% of intracellular trypsin activity.

Chymotrypsin C can also lyse and inactivate trypsin.

TRANSCRIBERS Group 8 EDITOR EINA.MARK.DADO

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ACUTE PANCREATITIS
 The incidence of acute pancreatitis also varies in different
countries and depends on cause (e.g., alcohol, gallstones,
metabolic factors, drugs )
 13–45/100,000/ year
 results in >250,000 hospitalizations per year.
 The median length of hospital stay is 4 days, a mortality of 1%.
 increase with age, are 88% higher among blacks
 Males> females.
 increasing and is a significant burden on health care costs and
resource utilization.

ETIOLOGY AND PATHOGENESIS

 GALLSTONE30-60%, <5mm-4X greater risk
 ALCOHOL 15-30% (1/100,000)
 POST ERCP 5-10%
 HYPERTRIGLYCEDIMIA 1.3–3.8% of
serum triglyceride levels are usually
>11.3 mmol/L (>1000 mg/dL).
 prone to recurrent episodes of pancreatitis
 DRUG RELATED 0.1–2%
 interstitial pancreatitis(pancreas blood supply maintained),
which is generally self-limited to
 necrotizing pancreatitis  (pancreas blood supply
interrupted), in which the extent of necrosis may correlate with
the severity of the attack and its systemic complications

AUTODIGESTION
 is a currently accepted pathogenic theory
 pancreatitis results when proteolytic enzymes (e.g.,
trypsinogen, chymotrypsinogen, proelastase, and lipolytic
enzymes such as phospholipase A2) are activated in the
pancreas acinar cell rather than in the intestinal lumen.
 A number of factors (e.g., endotoxins, exotoxins, viral
infections, ischemia, oxidative stress, lysosomal calcium, and
direct trauma) are believed to facilitate premature activation of
trypsin.
 Activated proteolytic enzymes, especially trypsin, not only
digest pancreatic and peripancreatic tissues but also can
activate other enzymes, such as elastase and phospholipase A2

ACTIVATION OF PANCREATIC ENZYMES

INITIAL PHASE
 is characterized by intrapancreatic digestive enzyme activation
and acinar cell injury.
 acinar cell injury is the consequence of trypsin activation.

SECOND PHASE
 activation, chemoattraction, and sequestration of leukocytes
and macrophages in the pancreas, resulting in an enhanced
intrapancreatic inflammatory reaction.

THIRD PHASE
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 Activated proteolytic enzymes, especially trypsin, not only

digest pancreatic and peripancreatic tissues but also activate
other enzymes such as elastase and phospholipase A2.
 The active enzymes and cytokines then digest cellular
membranes and cause proteolysis, edema, interstitial
hemorrhage, vascular damage, coagulation necrosis, fat
necrosis, and parenchymal cell necrosis.
 Cellular injury and death result in the liberation of bradykinin
peptides, vasoactive substances, and histamine that can
produce vasodilation, increased vascular permeability, and
edema with profound effects on many organs.
 The systemic inflammatory response syndrome (SIRS) and
acute respiratory distress syndrome (ARDS), as well as
multiorgan failure, may occur as a result of this cascade of local
and distant effects.

APPROACH TO THE PATIENT:

LABORATORY DATA
Abdominal pain
 Amylase and lipase- 3x elevated
 major symptom pain may vary from a mild discomfort to
 Lipase- preffered test
severe, constant, and incapacitating distress. steady and boring
in character, is located in the epigastrium and periumbilical and  After 3–7 days even with continuing evidence of pancreatitis,
may radiate to the back, chest, flanks, and lower abdomen. total serum amylase values tend to return toward normal.
 Nausea, vomiting, and abdominal distention due to gastric and  7–14 dayspancreatic isoamylase and lipase may remain
intestinal hypomotility and chemical peritonitis elevated
Physical examination  acidemia (arterial pH ≤7.32) may have spurious elevations in
 distressed and anxious patient serum amylase.
 Low-grade fever  Leukocytosis (15,000–20,000 leukocytes/μL) occurs frequently.
 Tachycardia  hemoconcentration
 hypotension Shock  In more severe disease, hematocrit >44%
 Hypovolemia secondary to exudation of blood and prerenal azotemia nitrogen (BUN) level >22 mg/dL
plasma proteins into the retroperitoneal space  significant risk factor for mortality.
 increased formation and release of kinin peptides,  Hyperglycemia
which cause vasodilation and increased vascular  Hypocalcemia occurs in ~25% of patients
permeability  Hyperbilirubinemia - (serum bilirubin >68 mmoL or >4.0 mg/dL)
 systemic effects of proteolytic and lipolytic enzymes occurs in ~10% of patients.
released into the circulation.  Alk phosphatase and AST elevated
 Jaundice occurs infrequently when present, it usually is due to  Hypertriglyceridemia- occurs in 5–10% of patients
edema of the head of the pancreas with compression of the  hypoxemia - Approximately 5–10% of patients (arterial PO2 ≤60
intrapancreatic portion of the common bile duct or passage of mmHg), which may herald the onset of ARDS.
a biliary stone or sludge.  12LECG- ST-segment and T-wave abnormalities simulating
 Erythematous skin nodules due to subcutaneous fat necrosis myocardial ischemia.
may rarely occur.
 In 10–20% of patients, there are pulmonary findings, including DIAGNOSIS
basilar rales, atelectasis, and pleural effusion, the latter most The diagnosis is established by two of the following three criteria:
frequently left sided. (1) typical abdominal pain in the epigastrium that may radiate
 Abdominal tenderness and muscle rigidity are present to a to the back
variable degree, but compared with the intense pain, these (2) threefold or greater elevation in serum lipase and/or
signs may be less impressive. Bowel sounds are usually amylase
diminished or absent. (3) confirmatory findings of acute pancreatitis on cross-
 4–6 weeksan enlarged pancreas from acute fluid collection, sectional abdominal imaging.
walled off necrosis, or a pseudocyst may be palpable in the nausea, emesis, fever, tachycardia
upper abdomen
Cullen’s sign A faint blue discoloration around the umbilicus may occur Phases of Acute Pancreatitis
as the result of hemoperitoneum. EARY (<2 weeks)
Turner’s sign  blue red-purple or green-brown discoloration of the  severity is defined by clinical parameters rather than
flanks, reflects tissue catabolism of hemoglobin from severe necrotizing morphologic findings.
pancreatitis with hemorrhage.  Most patients exhibit SIRS, and if this persists, patients are
EDITOR EINA.MARK.DADO predisposed to organ failure.
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 3organ systems should be assessed to define organ failure:  but may develop a local complication such as a fluid collection
respiratory, CV, and renal. that requires a prolonged hospitalization for >1 week.
 Organ failure : 2 or more for one of these three organ systems
using the modified Marshall scoring system. SEVERE ACUTE PANCREATITIS
 Persistent organ failure (>48 h) is the most important clinical  persistent organ failure (>48 h).
finding in regard to severity of the acute pancreatitis episode  Organ failure can be single or multiple.
 CT imaging is usually not needed or recommended during the  A CT scan or MRI should be obtained to assess for necrosis
first 48 h of admission in acute pancreatitis and/or complications.
 If a local complication is encountered, management is dictated
LATE (>2 weeks) by clinical symptoms, evidence of infection, maturity of fluid
 characterized by a protracted course of illness collection, and clinical stability of the patient.
 require imaging to evaluate for local complications.  Prophylactic antibiotics are not recommended!
 clinical parameter of severity: is persistent organ failure. IMAGING IN ACUTE PANCREATITIS
 supportive measures: renal dialysis, ventilator support, or 3–5 days into hospitalization when patients are not responding to
supplemental nutrition via the nasojejunal or parenteral route. supportive care to look for local complications such as necrosis.
 The radiographic feature of greatest importance to recognize in
this phase is the development of necrotizing pancreatitis on CT
imaging.
 Necrosis generally prolongs hospitalization and, if infected,
may require operative, endoscopic, or percutaneous
intervention.

SEVERITY OF ACUTE PANCREATITIS

MILD ACUTE PANCREATITIS
 No local complications or organ failure.
 Most patients with interstitial acute pancreatitis have mild Two types of pancreatitis are recognized on imaging as interstitial or
course necrotizing based on pancreatic perfusion
 self-limited and subsides spontaneously,usually within 3–7 A. Note the abnormal enhancement of the pancreatic
days after treatment is instituted. parenchyma (arrow) suggestive of interstitial pancreatitis.
 Oral intake can be resumed if the patient is hungry, has normal B. B. Contrast-enhanced CT scan of the abdomen performed on
bowel function, and is without nausea and vomiting. the same patient 6 days later for persistent fever and systemic
 Typically, a clear or full liquid diet: initial meal inflammatory response syndrome. The pancreas now
 a low-fat solid diet is a reasonable choice following recovery demonstrates significant areas of nonenhancement consistent
from mild acute pancreatitis. with development of necrosis, particularly in the body and neck
region (arrow). Note that an early CT scan obtained within the
MODERATELY SEVERE first 48 h of hospitalization may underestimate or miss
 Transient organ failure (resolves in <48 h) or local or systemic necrosis.
complications in the absence of persistent organ failure. C. C. Contrast-enhanced CT scan of the abdomen performed on
 With or without necrosis the same patient 2 months after the initial episode of acute
pancreatitis. CT now demonstrates evidence of a fluid
collection consistent with walledoff pancreatic necrosis

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A. Partially enhancing body/tail of pancreas surrounded by fluid with

decreased enhancement
in the neck/body of the pancreas.
B. Acute fluid collection: CT scan. Contrast-enhanced CT scan showing
fluid collection in the retroperitoneum (arrow) compressing the air-filled
stomach arising from the pancreas in a patient with asparaginase-
induced acute necrotizing pancreatitis.
C. Walled-off pancreatic necrosis: CT scan. CT scan showing marked
walled-off necrosis of the pancreas and peripancreatic area (arrow) in a
patient with necrotizing
pancreatitis. Addendum: In past years, both of these CT findings (Figs.
371-2B and 371-2C ) would have been misinterpreted as pseudocysts.
D. Spiral CT showing a pseudocyst(small arrow) with a pseudoaneurysm
(light area in pseudocyst). Note the demonstration of the main
pancreatic duct (big arrow), even though this duct is minimally dilated by
ERCP.
ACUTE PANCREATITIS MANAGEMENT
 85–90% of cases are self-limited and subside spontaneously
 usually within 3–7 days after initiation of treatment, and do
not exhibit organ failure or local complications.

Fluid Resuscitation and Monitoring Response to Therapy

 NPO to rest the pancreas
 intravenous narcotic analgesics to control abdominal pain
 O2 support at (2 L) via nasal cannula.
 Intravenous fluids of lactated Ringer’s or normal saline are
initially bolused at 15–20 cc/kg (1050–1400 mL), followed by 3
mg/kg per hour (200–250 mL/h), to maintain urine output >0.5
cc/kg per hour.
 VS q6–8 h to assess vital signs, oxygen saturation, and change
in PE
 hematocrit and BUN every 8–12 h
 decrease in hematocrit and BUN during the first 12–24 h is
strong evidence that sufficient fluids are being administered

Assessment of Severity and Hospital Triage

BISAP SCORE (Bedside Index of ICU
Severity in Acute Pancreatitis)
Interstitial pancreatitis occurs in 90–95%  BUN >25 mg/dL  patients with persistent SIRS
Necrotizing pancreatitis occurs in 5–10%  impaired mental status at 24 h or underlying
(Glasgow coma score <15) comorbid illnesses
 SIRS (e.g.,COPD, CHF)
 age >60 years  Patients with higher BISAP
 pleural effusion scores
 elevated hematocrit  elevations in haematocrit
>44% and admission BUN that do
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 and admission BUN >22 not respond to initial fluid  control of diabetes, administration of lipid-lowering
mg/Dl resuscitation agents, weight loss, and avoidance of drugs that
 three or more of these  evidence of respiratory elevate lipid levels
factors was associated with failure, hypotension, or
substantially increased risk organ failure
for in-hospital mortality

Special Considerations Based on Etiology

 liver profile, serum triglycerides, serum calcium), and an Nutritional Therapy
abdominal ultrasound are recommended in the ER  mild acute pancreatitis - low-fat solid diet can be administered
Gallstone pancreatitis to after the abdominal pain has resolved.
 Patients with evidence of ascending cholangitis (rising Enteral nutrition 2–3 days after admission in subjects with more
white blood cell count, increasing liver enzymes) severe pancreatitis instead of total parenteral nutrition (TPN).
should undergo ERCP within 24–48 h of admission. Enteral feeding:
 increased risk of recurrence  maintains gut barrier integrity
 cholecystectomy during the same admission or  limits bacterial translocation
within 4–6 weeks of discharge.  is less expensive
 Alternative: endoscopic biliary sphincterotomy  fewer complications
Hypertriglyceridemia
 Serum TG s >1000 mg/dLassociated with acute
pancreatitis.
 Initial therapy may include insulin, heparin, or
plasmapheresis.

MANAGEMENT OF LOCAL COMPLICATIONS sterile necrosis

NECROSIS - is most often managed conservatively unless complications
 Percutaneous aspiration of necrosis-W/ Gram stain and culture arise.
should be performed if there are ongoing signs of possible infected necrosis
pancreatic infection such as sustained leukocytosis, fever, or  established and an organism identified, targeted antibiotics
organ failure. should be instituted.
 no role for prophylactic antibiotic in necrotizing pancreatitis  Pancreatic debridement (necrosectomy) -definitive
 reasonable to start broad-spectrum antibiotics in a patient management
who appears septic  If conservative therapy can be safely implemented for 4–6
UNRESPONSIVE TO THERAPHY weeks, to allow the pancreatic collections to resolve or “wall-
 Repeat FNA and GC/CS of pancreatic necrosis may be done off,”SURGERY!
every 5–7 days in the presence of persistent fever
 Repeated CT or MRI imaging should also

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 stellate cell activation that results in cytokine expression and

RECURRENT PANCREATITIS production of extracellular matrix proteins cause acute and
 Approximately 25% of patients who have had an attack of acute chronic inflammation and collagen deposition in the pancreas.
pancreatitis have a recurrence  presence of histologic abnormalities, including chronic
 The two most common etiologic factors :alcohol and inflammation, fibrosis, and progressive destruction of both
cholelithiasis exocrine and eventually endocrine tissue (atrophy).
 OTHERS: microlithiasis, hypertriglyceridemia, drugs, pancreatic  cardinal manifestations: abdominal pain, steatorrhea, weight
cancer, pancreas divisum, and cystic fibrosis loss, and diabetes mellitus
 Approximately 2–4% of patients with pancreatic carcinoma  alcohol has been believed to be the primary
present with acute pancreatitis  Smoking is an independent, dose-dependent risk factor for
chronic pancreatitis and recurrent acute pancreatitis
CHRONIC PANCREATITIS  alcoholism is the most common among adults in the U.S,
 disease process characterized by irreversible damage to the  Cystic fibrosis -is the most frequent cause in children.
pancreas as distinct from the reversible changes noted in acute  25%-idiopathic form.
pancreatitis.  15% of patients with idiopathic pancreatitis may have
pancreatitis due to genetic defects.

Patients with chronic pancreatitis seek medical attention predominantly

AUTOIMMUNE PANCREATITIS because of two symptoms:
 uncommon disorder of presumed autoimmune causation with  abdominal pain or maldigestion
characteristic laboratory, histologic, and morphologic findings.  weight Loss.
The Mayo Clinic HISORt criteria indicate that AIP can be diagnosed by abdominal pain
the presence of at least two of the following:  variable in location, severity, and frequency.
(1) histology  constant or intermittent with frequent pain-free intervals.
(2) imaging  The spectrum of abdominal pain ranges from mild to quite
(3) serology (elevated serum IgG4 levels) severe, with narcotic dependence as a frequent consequence
(4) other organ involvement  Eating may exacerbate the pain, leading to a fear of eating
(5) response to glucocorticoid therapy, with improvement in with consequent weight loss.
pancreatic and extrapancreatic manifestations. Maldigestion:
 chronic diarrhea
 Steatorrhea
 weight loss
 fatigue.

DIAGNOSIS
 amylase and lipase levels not strikingly elevated .
 Inc bilirubin and alkaline phosphatasecaused by chronic
inflammation.
 impaired glucose tolerance with elevated fasting blood glucose
levels.
 The fecal elastase-1 and small-bowel biopsy are useful in the
evaluation of patients with suspected pancreatic steatorrhea.
 decrease of fecal elastase level to <100 μg per gram of stool
strongly suggests severe pancreatic exocrine insufficiency.
 Abdominal CT scan
CLINICAL FEATURES OF CHRONIC PANCREATITIS EDITOR EINA.MARK.DADO
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 MRI
 Endoscopic ultrasound
 pancreas function testing

TREATMENT Chronic Pancreatitis

STEATORRHEA
 Enzyme therapy
 80,000–100,000 units of lipase taken during the meal
ABDOMINAL PAIN
 high concentrations of serine proteases
 Gastroparesis- pregabalin
Endoscopic treatment : sphincterotomy, stenting, stone extraction, and
drainage of a pancreatic pseudocyst.
 80% seem to obtain immediate relief
Whipple procedure, total pancreatectomy, and autologous islet cell
transplantation have been used in selected patients with chronic
pancreatitis and abdominal pain refractory to conventional therapy.

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