Acute Pancreatitis Flashcards
Pathophysiology
AP is the final result of abnormal pancreatic enzyme activation inside acinar cells
What is an Early step before elevation of amylase and lipase ?
> > zymogen and lysosome colocalization occurs before amylase level elevation, pancreatic edema, and other markers of pancreatitis are evident suggests that colocalization is an early step in the pathophysiologic process
Role of Cathepsin B
> > cathepsin B that then induces apoptosis or necrosis, leading to acinar cell death.
> > Thus, acinar cell death and to a degree the inflammatory response seen in AP can be prevented if acinar cells are pretreated with cathepsin B inhibitors.
What happens to the Protective mechanism ?
> > Intraacinar pancreatic enzyme activation induces autodigestion of normal pancreatic parenchyma.
> > release proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-1, IL-2, and IL-6, and antiinflammatory mediators, such as IL-10 and IL-1 receptor antagonist.
> > propagate the response locally and systemically
What frequently seen in patients with severe pancreatitis
> > Active neutrophils mediate acute lung injury and induce the adult respiratory distress syndrome frequently seen in patients with severe pancreatitis
The mortality seen in the early phase of pancreatitis is the result of
persistent inflammatory response
RF ?
- Gallstones and ethanol abuse account for 70% to 80% of AP cases.
- In pediatric patients, abdominal blunt trauma and systemic diseases are the two most common conditions that lead to pancreatitis.
- Autoimmune and drug-induced pancreatitis should be a differential diagnosis in patients with rheumatologic conditions such as systemic lupus erythematosus and Sjögren syndrome
most common cause of AP in the West
Gallstone pancreatitis is the most common cause of AP in the West
Two theories have been proposed
> > obstructive theory, pancreatic injury is the result of excessive pressure inside the pancreatic duct
> > Reflux, theory proposes that stones become impacted in the ampulla of Vater and form a common channel that allows bile salt reflux into the pancreas.
Alcohol damages the pancreas through multiple mechanisms:
- Inflammation → Activates NF-κB, TNF-α, IL-1
- Enzyme Misrelease → Causes zymogen exocytosis at the wrong site
- Autophagy Dysregulation → Due to cathepsin L & B imbalance
- Oxidative Stress → Leads to mitochondrial dysfunction
- Fibrosis → Activates pancreatic stellate cells (PSCs), increasing matrix metalloproteases
- Impaired Repair → Affects PDX1, PTF1a, Notch
- Cell Death Shift → From apoptosis to necrosis due to ↓ caspase 3/8 & ATP loss
Anatomic Obstruction
> > Pancreas divisum is an anatomic variation present in 10% of the population.
caused by relative outflow obstruction through the minor papilla.
(ERCP) with minor papillotomy and stenting may be beneficial for such patients.
> > Infrequent anatomic obstructions that have been associated with AP include Ascaris lumbricoides infection and annular pancreas.
what can be done to prevent ercp pancreatitis ?
> > indomethacin
pancreatic stents
using minimal pressure while performing ERCP
ERCP
- AP is the most common complication after ERCP, occurring in up to 5% of patients
- PostERCP pancreatitis is more common in
»female patients
»young individuals
»patients with prior history of ERCP induced pancreatitis.
> > AP occurs more frequently in therapeutic procedures
who have had multiple attempts of cannulation,
sphincter of Oddi dysfunction
abnormal visualization of the secondary pancreatic ducts after injection of contrast material.
Drug-Induced Pancreatitis
- sulfonamides
- metronidazole
- erythromycin
- tetracyclines
- didanosine
- thiazides
- furosemide
- 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins)
- azathioprine
- 6-mercaptopurine
- 5-aminosalicylic acid
- sulfasalazine
- valproic acid
- human immunodeficiency virus antiretroviral agents
Metabolic Factors
- Hypertriglyceridemia and hypercalcemia
> > more common in patients with type I, II, or V hyperlipidemia.
suspected triglyceride level higher than 1000 mg/dL.
higher than 2000 mg/dL confirms the diagnosis.
- Hypercalcemia»_space; activation of trypsinogen to trypsin and intraductal precipitation of calcium
> > Approximately 1.5% to 13% of patients with primary hyperparathyroidism develop AP
Miscellaneous Conditions
-Blunt and penetrating abdominal trauma
-intraoperative hypotension and excessive pancreatic manipulation
-Pancreatic ischemia in association with acute pancreatic inflammation can develop after splenic artery embolization
-Scorpion Venom
-Perf DU
indicative of retroperitoneal bleeding
Rare findings include flank and periumbilical ecchymosis (Grey Turner and Cullen signs, respectively)
diagnosis of AP
2 out of 3 :
1) abdominal pain consistent with AP (acute onset of a persistent, severe, epigastric pain often radiating to the back)
2) threefold or higher elevation of serum amylase or lipase levels above the upper laboratory limit of normal
3) characteristics findings of pancreatitis by imaging.
The serum half-life of amylase and lipase
The serum half-life of amylase (10 hours)
lipase (6.9–13.7 hours)
normalizes faster (3–5 vs. 8–14 days, respectively).
Lipase Vs Amylase
> > In patients who do not present to the emergency department within the first 24 to 48 hours after the onset of symptoms, determination of lipase levels is a more sensitive indicator to establish the diagnosis.
Lipase is also a more specific marker of AP
Amylase can be elevated in
peptic ulcer disease and mesenteric ischemia
ALT ??
The elevation of alanine aminotransferase levels in the serum in the context of AP confirmed by high pancreatic enzyme levels has a positive predictive value of 95% in the diagnosis of acute biliary pancreatitis
simple abdominal radiographs
- air-fluid levels suggestive of ileus
- cutoff colon sign as a result of colonic spasm at the splenic flexure
- widening of the duodenal C loop caused by severe pancreatic head edema
Indications for CT include
- diagnostic uncertainty
- confirmation of severity based on clinical predictors,
- failure to respond to conservative treatment
- clinical deterioration.
The most valuable contrast phase in which to evaluate the pancreatic parenchyma is the portal venous phase
(65–70 seconds after injection of contrast material)
MRCP indications
- evaluation of patients with unexplained or recurrent pancreatitis because it allows noninvasive complete visualization of the biliary and pancreatic duct anatomy.
- For difficult to view pancreatic ducts, intravenous (IV) administration of secretin can be injected prior to imaging to stimulate pancreatic juice secretion, thereby causing a transient distention of the pancreatic duct.
> > pancreas divisum, intraductal papillary mucinous neoplasm (IPMN), or a small tumor in the pancreatic duct
EUS ??
has been proven to be sensitive for identifying choledocholithiasis;
it allows examination of the biliary tree and pancreas with no risk of worsening of the pancreatitis.
Ranson Criteria
> > Severe pancreatitis is diagnosed if three or more of the Ranson criteria are fulfilled.
low positive predictive value (50%) and high negative predictive value (90%)
used to rule out severe pancreatitis or to predict the risk of mortality.
APACHE II Score ?
- An APACHE II score of eight or higher defines severe pancreatitis.
- The main advantage is that it can be used on admission and repeated at any time.
- not specific for AP, and based on the patient’s age, which easily upgrades the AP severity score
The CT severity index
CTSI 0–3, mortality 3%, morbidity 8%;
CTSI 4–6, mortality 6%, morbidity 35%;
CTSI 7–10, mortality 17%, morbidity 92%
SIRS
> > fast, inexpensive, and reliable replacement.
> > persistent SIRS throughout hospital admission,
> > having a transient SIRS
> > never meeting SIRS criteria has been
> > mortality rates of 25%, 8%, and 0%, respectively
Mild , Mod, severe Pancreatiis
> > Mild pancreatitis has no organ dysfunction or local/systemic complications
> > moderate pancreatitis can have organ failure lasting less than 48 hours and/or local/systemic complications,
> > severe pancreatitis is characterized by organ failure lasting beyond 48 hours.
What inflammatory marker correlate with severity
> > C-reactive protein (CRP)
peaks 48 to 72 hours after the onset of pancreatitis
correlates with the severity of the disease.
> > A CRP level of 150 mg/mL or higher defines severe pancreatitis.
The major limitation is that it cannot be used on admission
the sensitivity of the assay decreases if CRP levels are measured within 48 hours after the onset
Atlanta criteria for acute pancreatitis
Organ Failure, as Defined by
Shock (systolic blood pressure <90 mm Hg)
Pulmonary insufficiency (PaO 2 <60 mm Hg)
Renal failure (creatinine level >2 mg/dL after fluid resuscitation)
Gastrointestinal bleeding (>500 mL/24 hour)
Systemic Complications
Disseminated intravascular coagulation (platelet count ≤100,000)
Fibrinogen <1 g/L
Fibrin split products >80 μg/dL
Metabolic disturbance (calcium level ≤7.5 mg/dL)
Local Complications
Necrosis
Abscess
Pseudocyst
Severe pancreatitis is defined by the presence of any evidence of organ failure or a local complication
Tx ?
aggressive fluid resuscitation with isotonic crystalloid solution, pain control, and early nutrition.
» Narcotics are usually preferred, especially morphine
» however, there is no evidence that narcotics exert a negative impact on the outcome of patients with AP.
invasive monitoring with central venous access and a Foley catheter
continuous pulse oximetry
Ringer’s lactate may be the best fluid for initial resuscitation.
Rate of Fluids?
adjusted on the basis of age, comorbidities, vital signs, mental status, skin turgor, and urine output
Enteral Vs TPN ?
> > enteral nutrition
- fewer infectious complications and reduces the need for pancreatic surgery.
> > TPN provides most nutritional requirements
- associated with mucosal atrophy
- decreased intestinal blood flow
- increased risk of bacterial overgrowth in the small bowel
- antegrade colonization with colonic bacteria
- increased bacterial translocation. In addition
- central line infections
- metabolic complications
(e.g., hyperglycemia, electrolyte imbalance).
> > Nasojejunal feeding tube placement is currently favored,
Abx ?
Current recommendations are to only administer antibiotics if a preexisting infection is present on presentation or radiographic imaging suggests infected peripancreatic fluid collections (e.g., air within collection or rim enhancement)
Why Early ERCP not recommended ?
> > the bile duct obstruction is usually transient and resolves within 48 hours after the onset of symptoms.
ERCP is only indicated for
> > who develop cholangitis
persistent bile duct obstruction demonstrated by other imaging modalities, such as EUS.
older patients with poor performance status or severe comorbidities that preclude surgery - to prevent recurrent biliary pancreatitis.
What percentage will have recurrent pancreatitis ?
> > 30%
Lap chole Same admission
> > For patients with severe pancreatitis, early surgery may increase the morbidity and length of stay.
Current recommendations suggest conservative treatment for at least 6 weeks before laparoscopic cholecystectomy
Fluid collections ?
> > Acute peripancreatic fluids collections are simple in nature
after four weeks are referred to as a pseudocyst.
> > Fluid collections associated with necrotizing pancreatitis are referred to as an acute necrotic collection (ANC) before four weeks
walled off necrosis after that period.
Tx of Collections ?
> > supportive because most fluid collections will be spontaneously reabsorbed by the peritoneum.
fever, elevated white blood cell count, and abdominal pain may also be present without an infection
> > Evidence of gas within a fluid collection on imaging is highly suggestive.
Acute decompensation or failure to improve after 10 to 14 days may suggest infection and consideration should be given to CT-guided fluid sampling
When to start abx, and what abx ?
> > Drainage (percutaneous or endoscopic) and IV administration of antibiotics should be instituted if infection is present.
> > Antibiotics known to penetrate pancreatic necrosis include carbapenems, quinolones, metronidazole, and high-dose cephalosporins.
Main Complication of Acute necrotic collection
- directly related to the amount of necrosis
- the more the necrosis the high chance of infection
- bacterial translocation usually involving enteric flora, such as gram-negative rods
(e.g., Escherichia coli, Klebsiella, and Pseudomonas spp.) and Enterococcus spp
How to diagnosis Necrosis ?
> > areas of low attenuation (<40–50 HU) after the IV injection of contrast material
> > Normal parenchyma usually has a density of 100 to 150 HU
When to suspect Infected necrosis ?
> > if the patient develops sepsis, SIRS, and/or organ failure later in the course of the disease (>7 days after the onset of the AP).
> > Evidence of air within the pancreatic necrosis seen on a CT scan confirms the diagnosis but is a rare finding.
> > If infected necrosis is suspected, fine-needle aspiration (FNA) may be performed if the diagnosis is equivocal;
> > from the aspirate, a positive Gram stain or culture establishes the diagnosis
CT peripancreatic fluid Vs necrotic collection
Interstitial edematous + Acute peripancreatic fluid collection
* Homogeneous collection with fluid density
* Confined by normal peripancreatic fascial planes
* No definable wall encapsulating the collection
* Adjacent to pancreas (no intrapancreatic extension)
Necrotizing + Acute necrotic collection
* Heterogeneous and nonliquid density of varying degrees in different locations (some appear homogeneous early in their course)
* No definable wall encapsulating the collection
* Location—intrapancreatic and/or extrapancreatic
Pseudocyst Vs Walled-off necrosis
Pseudocyst
* Well circumscribed, usually round or oval
* Homogeneous fluid density
* No nonliquid component
* Well-defined wall; that is, completely encapsulated
Walled-off necrosis
* Heterogeneous with liquid and nonliquid density with varying degrees of loculations (some may appear homogeneous)
* Well-defined wall; that is, completely encapsulated
* Location—intrapancreatic and/or extrapancreatic
Indications for intervening in sterile necrotizing pancreatitis
- persistent pain
- failure to improve clinically with conservative management
- symptomatic biliary or enteric obstruction.
> > Intervention for these indications should be delayed as much as possible to allow development of walled off necrosis.
clinical suspicion of or documented infected necrotic collection with clinical deterioration is a clear indication for intervention.
Timing for Open surgery and mortality
> > surgery in the first 14 days have a mortality rate of 75%,
surgery between 15 and 29 days have mortality rates of 45%
after 30 days 8%
Pathophysiology of infected necrosis ?
> > inflammatory injury causes mucosal ischemia and reperfusion injury.
bacterial overgrowth
increase in the permeability of intestinal cells
initiated 72 hours after the acute episode
transient episodes of bacteremia are associated with pancreatic necrosis infection.
> > distant sources of infection, such as pneumonia and vascular or urinary tract infection associated with central lines and catheters, are associated with bacteremia and pancreatic necrosis.
local contamination after surgery or interventional procedures such as endoscopic retrograde cholangiopancreatography is responsible for necrosis infection.
“step-up approach”
> > percutaneous drainage
followed by minimally invasive video-assisted retroperitoneal debridement for necrotizing and infected necrotizing pancreatitis.
> > The results showed that long-term end-point complications (e.g., exocrine and endocrine insufficiency) and mortality rates were better in the “step-up approach”
> > Currently, an endoscopic drainage with a large-bore stent and possible endoscopic debridement with or without percutaneous drainage can avoid an operation in most patients.
If the endoscopic and/or percutaneous management fails, a minimally invasive operation will usually be more straightforward
