Acute Pancreatitis Flashcards
what is the difinition of acute inflammation of the pancreas ?
abdominal pain and elevated pancreatic enzymes
what are the two main etiologies behind acute pancreatitis ?
gallstones and alcohol consumption
2/3 of cases
explain the mechanism behind biliary lithiasis
- obstruction of Ambullae Vatter with gallstones
- Transitory obstruction +/- edema of Amp. Vatter
Where does alcohol metabolization occur?
Liver (oxidative pathway) and Pancreas (non-oxidative pathway)
What is produced in the pancreas during alcohol metabolization?
Toxic metabolites (acetaldehyde and fatty acid esters)
What do these toxic metabolites (acetaldehyde and fatty acid esters) do in the pancreas?
accumulate
What are four mechanisms by which alcohol contributes to acute pancreatitis?
Increased acinar cell sensibility to cholecystokinin (CCK)
Increased pancreatic and lysosomal enzyme synthesis in acinar cells, secondary to toxic metabolite accumulation
Altered calcium homeostasis
Activation of stellate cells - increased
production of collagen and proteins of ECM
What are two metabolic causes of acute pancreatitis (AP)?
Hypertriglyceridemia and hypercalcemia
At what triglyceride level does hypertriglyceridemia (HTG) induce AP?
> 1000mg/dL
How does hypertriglyceridemia (HTG) lead to AP?
Pancreatic lipase metabolizes triglycerides (TRG) into free fatty acids (FFA), which are toxic in high concentrations.
What are the two types of hypertriglyceridemia (HTG)?
Primary HTG (familial/hereditary) and Secondary HTG
Give examples of secondary hypertriglyceridemia (HTG).
Uncontrolled diabetes, drugs (estrogen-tamoxifen), pregnancy, alcohol
What combination often leads to AP?
Primary HTG + Secondary cause
How does hypercalcemia contribute to AP?
Intraductal calcium deposits + activation of trypsinogen inside acinar cells.
What is the typical latency period for drug-induced AP?
After weeks/months of exposure
What are some mechanisms by which drugs can induce AP?
Immune reactions, direct toxic effect on the pancreatic duct, ischemia, ↑ viscosity of pancreatic juice, intravascular thrombosis
Give examples of drugs/drug classes and their associated mechanisms for inducing AP.
Immune reactions: aminosalicylates, 6MP
Direct toxic effect on pancreatic duct: diuretics
Ischemia, ↑ viscosity of pancreatic juice: diuretics
Intravascular thrombosis: estrogens
low mortality and good prognosis
List some viruses that can cause acute pancreatitis
Mumps, Coxsackie, CMV
What bacteria is associated with acute pancreatitis?
Mycobacterium
Name a fungus that can cause acute pancreatitis.
Aspergillus
What parasite is associated with acute pancreatitis?
Toxoplasma
What toxin is specifically mentioned as a cause of acute pancreatitis?
Scorpion venom
What conditions can ischemic pancreatitis be associated with?
Vasculitis and Hemorrhagic shock
Name a congenital defect of the pancreatic ducts that can lead to acute pancreatitis.
pancreas divisum
Describe the duct formation in Pancreas Divisum.
Formation of a major (dorsal) Santorini duct that drains through papilla minor
What does Pancreas Divisum lead to?
Intraductal hypertension
What genetic condition is associated with Pancreas Divisum?
cystic fibrosis
Iatrogenic causes ?
post ERCP
How can hereditary pancreatitis present?
AP in childhood, without a clear cause OR Recurrent AP at a young age (<35yo)
What does the PRSS1 gene mutation do, and what does it codify?
Codifies TRIPSINOGENUL and causes premature activation of pancreatic zymogens inside the pancreas.
What does the CFTR gene mutation do, and what does it stand for?
Cystic Fibrosis Transmembrane Conductance Regulator, leads to viscous pancreatic juice causing ductal obstruction.
What does the SPINK1 gene mutation affect?
Pancreatic secretory trypsin inhibitor.
Why is pancreatic duct injury rare?
Retroperitoneal localization of the pancreas
What can abdominal trauma cause
Can injure the pancreas
What can rupture of the pancreatic duct lead to?
Ascites
What can healing after pancreatic duct injury result in?
Ductal strictures
What are zymogens?
Inactive digestive enzymes secreted by the pancreas
How are zymogens deposited?
As vacuoles
Where are zymogens secreted?
In the duodenum through the pancreatic duct
What influences zymogen activity
pH-dependent activity
What are the mechanisms for neutralization of prematurely activated pancreatic enzymes?
Pancreatic secretory trypsin inhibitor (PSTI/SPINK) - neutralizes 20% of trypsin activity
Autolysis of premature form (deficient in hereditary forms of AP)
Mesotrypsin and Y enzyme: lytic proteases of trypsin
Nonspecific antiproteases: alpha-1
antitrypsin and alpha-2 macroglobulin
What is the first step in the pathophysiology of pancreatitis?
Increased lysosomal synthesis
What is inhibited at the apical pole in the pathophysiology of pancreatitis?
Zymogen exocytosis
What cytokine independently activates zymogens?
TNF-alpha
What enzyme from lysosomes activates trypsinogen?
Cathepsin B
What do Cathepsin B and trypsin activate when released in the cytosol?
Protein-kinases
What is a consequence of activated protein-kinases?
Cytochrome c mediated apoptosis (Mithocondria)
Membrane rupture, enzymatic leakage and necroptosis
What does Ca2+ released from ER promote physiologically
Apical exocytosis of zymogens and mitochondrial ATP synthesis
ow is accumulation of Ca2+ prevented?
SERCA - ATP-dep: reintroduces Ca2+ in the SER
PMCAs - ATP-dep: lowers intracellular Ca2+
What is a pathological consequence of intraacinary hypercalcemia
Premature activation of trypsinogen
What are the causes of intraacinary hypercalcemia?
Toxic effect of alcohol and biliary salt on SERCA and PMCA
Ductal hypertension (activation of mechanoreceptor-PIEZO1) - Ca2+ influx
What does intraacinary hypercalcemia produce?
Premature activation of trypsinogen
Perturbed membrane potential -> decreased ATP production
Hypofunction of ATP-dep SERCA and PMCAs, accumulation Ca2+
Acinar necrosis/apoptosis due to low ATP reserve
Acute pancreatitis evolution:
Intraacinary activation of proteolytic enzymes
Local microcirculation lesions
Leucocyte chemotaxis, cytokine secretion și ROS
SIRS
Bacterial translocation
What is a primary symptom in acute pancreatitis
Abdominal pain
What are the possible onsets of abdominal pain in acute pancreatitis
Acute (biliary AP) or progressive (alcoholic, metabolic, hereditary AP
What is the typical localization of abdominal pain in acute pancreatitis?
epigastric
What are the possible radiations of pain in acute pancreatitis?
Posterior, left hypochondrium, right hypochondrium
What antalgic position may a patient with acute pancreatitis assume?
Thorax anteflexion, orthostatism (standing upright)
What are some other symptoms that may accompany abdominal pain in acute pancreatitis?
Nausea and vomiting
What respiratory symptom can occur in acute pancreatitis?
Dypnea
What is the cause of dyspnea in acute pancreatitis
Diaphragm inflammation
restrictive syndrome
What thoracic condition can occur in acute pancreatitis
Left pleural effusion
What severe respiratory condition can develop as a result of SIRS in acute pancreatitis?
ARDS (Acute Respiratory Distress Syndrome)
What might jaundice indicate in acute pancreatitis?
Biliary AP or edema of the head
What do subcutaneous nodules indicate in acute pancreatitis
Fat tissue necrosis
What are the characteristics of subcutaneous nodules?
Red, painful, upper extremities
What do xanthelasma/xanthoma suggest in acute pancreatitis
Metabolic AP (Hypertriglyceridemia - HTG)
What conditions can cause parotid hypertrophy?
Alcoholic AP, Epidemic parotitis (Mumps)
What liver condition might be present in alcoholic AP?
hepatomegaly
What is a common sign of inflammation in acute pancreatitis?
Fever
in Severe AP
What change in blood pressure can occur in acute pancreatitis?
Hypotension (hTA)
in severe AP
What change in respiration rate can occur in acute pancreatitis?
Tachypnea
in severe AP
What skin discoloration can occur in severe cases of acute pancreatitis?
Cyanosis
Severe AP
What might abdominal enlargement suggest in acute pancreatitis?
Pancreatic ascites (pancreatic cyst rupture or pancreatic duct rupture)
What abdominal sign is associated with “paralitic” ileus?
Meteorism
What is the name of the paraumbilical ecchymoses seen in acute pancreatitis
Cullen sign
What is the name of the ecchymoses seen on the flanks in acute pancreatitis
Grey Turner sign
What might be noted on palpation of the abdomen in acute pancreatitis
Sensibility/pain at profound palpation in the epigastrum
What might dullness on percussion indicate?
Ascites
What might a hyperresonant sound on percussion indicate?
Ileus
Paraclinic explorations
Serology
Imagistic investigations
- Abdominal x-ray
- Abdominal US
- Abdominal CT
- ColangioMRI
What are the key characteristics of serum amylase in diagnosing acute pancreatitis?
Low specificity
Increases 6-12h from onset
T ½ short, 10h
What are the key characteristics of serum lipase in diagnosing acute pancreatitis?
High sensitivity and specificity
Increases 4-8h from onset
T ½ long, 8-14 days
What inflammatory markers are elevated in acute pancreatitis, and what does a high CRP at 48 hours indicate
CRP (>150mg/L at 48 h severe AP)
IL-6
IL-8
TNF
What is the typical abdominal x-ray finding in acute pancreatitis?
normal
What is a “sentinel loop” on an abdominal x-ray, and what does it indicate?
Dilation of a segment of the intestine secondary to ileus
Helps localize the inflammatory process (e.g., upper abdomen in AP)
What are other common lab findings in acute pancreatitis, besides amylase and lipase?
Leucocytosis and Ht (hemoconcentration)
Hypo/hyperglycemia
Elevated urea, creatinine
Low SpO2
What is the cause of hemoconcentration in acute pancreatitis?
Extravasation of intravascular fluid into surrounding tissue
What are common chest x-ray findings in acute pancreatitis?
Ascended left hemidiaphragm
Left pleural effusion
Basal atelectasis
What are the advantages and limitations of abdominal ultrasound in evaluating acute pancreatitis?
Widely spread and easy to use, but possible difficulty in evaluating the pancreas due to abdominal meteorism.
What are typical ultrasound findings in acute pancreatitis
Enlargement of the pancreas, nonhomogeneous echotexture, hyperechogenicity/hypoechogenicity (edematous AP).
Peripancreatic liquid.
When is an abdominal CT scan indicated in acute pancreatitis?
Only used if diagnosis is uncertain.
Mandatory if clinical deterioration after 48-72h to assess local complications (collections/necrosis).
What are the advantages and disadvantages of abdominal and cholangio-MRI in evaluating acute pancreatitis?
Pricy, not routinely used.
Superior to CT in evaluating biliary cause and local complications
Positive diagnosis
Clinic criterion: characteristic abdominal pain
Biologic criterion: Amylase or Lipase x3 normal value
Imagistic criterion: characteristic aspect (US, CT, IRM)
2/3 criteria are needed for diagnosis
Differential diagnosis
- Peptic ulcer
No radiation, intermittent , normal amylase/lipase
- Biliary colic/ acute cholecystitis
Radiation in RH, right shoulder
Murphy sign: pain when palpating the cystic point
Vesicular hydrops
- Appendicular colic
Epigastric pain (Initially), later- right iliac fossa
- Intestinal occlusion
Fecaloid vomit, absent intestinal sounds
Amylase, lipase <3x NV
Abdominal x-ray: hydro-aeric levels and intestinal distension
- Mesenteric ischemia
Intense periumbilical pain
Risk factors: elderly, systemic atheromatosis, arrythmia
Amylase, lipase <3x NV (CT for positive diagnosis)
- Intestinal perforation
Acute onset of pain
Signs of peritoneal irritation: abdominal guarding
Amylase <3x NV
Abdominal x-ray: pneumoperitoneum (air in the peritoneum)
- Acute hepatitis
Pain in RH ( painful hepatomegaly due to Glisson capsule distension)
AST,ALT> 1000 UI
- Inferior acute myocardial infarction
- Lower left inferior lobe pneumonia
- Renal colic
treatment
hospitalization
fluid replacement
pai control
mandatroy fasting
What is the recommended fluid replacement strategy for acute pancreatitis?
“Aggressive” hydration (5-10mL/kg/h crystalloid solution - normal saline or Ringer Lactate).
What are the benefits of aggressive hydration in acute pancreatitis?
Accelerates enzymatic and inflammatory clearance.
Maintains effective circulating plasma volume.
Most important initial management.
Reduces mortality in the first 24h (reduces SIRS, MSOF incidence).
What are the risks associated with aggressive hydration in acute pancreatitis?
Risk of pulmonary edema in cardiac patients.
Risk of compartment syndrome (aggressive hydration no more than 48-72h).
What are the therapeutic goals of fluid replacement in acute pancreatitis?
HR < 120 bpm, mAP > 65 mmHg, lowering BUN and Hct, normal diuresis.
revaluation after 6-24 h
When should Ringer Lactate be avoided during fluid replacement in acute pancreatitis?
In metabolic AP (hypercalcemia) due to its calcium content.
What class of medications is used for pain management in acute pancreatitis?
Opioid analgesics.
What is a preferred opioid analgesic in acute pancreatitis, and why
Fentanyl (25-50 μg) due to its safe renal profile
What are the potential drawbacks of using morphine for pain management in acute pancreatitis?
It can induce spasm of the Oddi sphincter, potentially aggravating acute pancreatitis.
What is an alternative opioid analgesic to morphine in acute pancreatitis, and why is it preferred?
Meperidine/Pethidine is preferred due to its higher safety profile (low T ½, no Oddi spasm).
What is a significant potential side effect of opioid analgesics?
Respiratory depression
Why is fasting mandatory in acute pancreatitis?
To stop stimulating pancreatic secretion.
When is a nasogastric tube indicated in acute pancreatitis?
To reduce gastric secretion or in patients with ileus.
What are the criteria for reinitiating oral alimentation in acute pancreatitis?
No pain (without analgesics)
No nausea or vomiting
No ileus
Hunger sensation
What is the preferred order of nutritional support in acute pancreatitis?
Oral nutrition > enteral nutrition > parenteral nutrition.
What is the initial diet progression after reinitiating oral alimentation in acute pancreatitis?
Initially, liquid diet, followed by a hypolipidic diet, low quantity meals.
When is enteral nutrition via naso-jejunal tube indicated in acute pancreatitis?
In severe forms of AP (without digestive tolerance).
Treatment of local complication
Treatment of necroses
Treatment of pseudocysts
Treatment of pseudoaneurysms
Treatment of thromboses
Treatment of pancreatic ascites
