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Question

We all know that nutritional supplementation during pregnancy is extremely important for fetal development. But…….there is one particular vitamin that can be teratogenic in excess doses.

1. What vitamin is this?
2. What types of foods are extremely high in this vitamin and why?

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Question

1. The class of retinoic acids have two main forms of vitamin A:
   1. Provitamin A – primarily plant based carotenoids
      1. green leafy vegetables, sweet potatoes, carrots
   2. Preformed vitamin A – primarily in animal sources
      1. livers, kidneys
2. Up to 85% of metabolized vitamin A is stored in the liver and other tissues due to being fat soluble. As a result, animal organs (liver, kidneys, thymus) are extremely high in preformed vitamin A and can cause acute and/or chronic toxicity when ingested in large quantities.

References

1. Rothman KJ, Moore LL, Singer MR, Nguyen UD, Mannino S, Milunsky A. Teratogenicity of High Vitamin A Intake N Engl J Med. 1995; 333(21):1369-1373.

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Question

We all know that nutritional supplementation during pregnancy is extremely important for fetal development. But…….there is one particular vitamin that can be teratogenic in excess doses.

1. What vitamin is this?
2. What types of foods are extremely high in this vitamin and why?

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Epidemiology

• 13-45 per 100,000 person incidence in the US
• Most common GI cause of hospital admission in the US
  • > 300,000 per year
  • Average 4-day stay with cost > $6000/case
• Equal gender representation across the lifespan
  • Alcohol pancreatitis more common in men
• 2-3 fold higher rates in African Americans

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Risk Factors and Etiologies

• Gallstones
  • 40-70% of cases
    • Only 3-7% of patients with gallstones develop pancreatitis
  • Two theorized mechanisms
    • Reflux of bile into the pancreatic duct
    • Obstruction at the ampulla
  • Magic number is 5mm
    • Small enough to pass through cystic duct, but still get obstructed at ampulla
• Alcohol
  • 25-35% of cases
  • Interesting data to show that it is not just alcohol that causes pancreatitis
    • 5 out of 100,00 patents with alcohol abuse develop pancreatitis
  • Several mechanisms theorized
    • Sensitization of acinar cell to CCK-induced activation of zymogens
    • Potentiation of the effect of CCK
    • Generation of toxic metabolites
    • Sensitization of the pancreas to toxic insults
    • Activation of pancreatic stellate cells to increase production of matrix proteins
• Idiopathic (genetic)
  • 15-25% of patients with pancreatitis have no identifiable pathologic cause
  • These cases are largely theorized to have complex genetic risk profiles
• Hypertriglyceridemia
  • 1-14% of cases
  • > 1000 mg/dL increases risk
• Post-ERCP
  • 3% of patients undergoing diagnostic ERCP
  • 5% of patients undergoing therapeutic ERCP
  • 25% of patients undergoing sphincter of Oddi measurements
• Medications
  • < 5% of cases
  • Classification system (Ia, Ib, II, III, IV)
  • Prognosis is excellent and mortality is very low
• Obesity
• Smoking
• Diabetes

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Pathogenesis

• Pancreatic enzymes synthesis continues while secretion is slowed or halted
• HIT #1 –  Intraacinar activation of proteolytic enzymes (trypsin)
  • Cascade of enzyme release and activation then occurs
  • Ultimately, causes autodigestion of the pancreas
• HIT #2 – Microcirculatory injury
  • Damage to the pancreas via autodigestion leads to vasoconstriction, decreased oxygenation, and progressive ischemia
    • Leads to edema and further decreased secretion of enzymes
• HIT #3 – Leukocyte infiltration, cytokine release, and oxidative stress
  • Leads to widespread inflammation and induce thrombosis and hemorrhage
  • Ultimately, causes necrosis
• Two main classifications
  • Interstitial pancreatitis – blood supply is maintained
  • Necrotizing pancreatitis – blood supply is affected

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Signs and Symptoms

• History
  • Epigastric pain
    • May radiate to the back
    • May radiate to the right shoulder
      • Kehr’s sign
  • Nausea
  • Vomiting
  • Dyspneic
    • Severe disease can cause diaphragmatic irritation and pleural effusions
• Physical Examination
  • Fever
  • Tachycardia
  • Epigastric tenderness
  • Abdominal distention
  • Hypoactive bowel sounds
  • Jaundiced
  • Abdominal ecchymosis (necrotizing disease)
    • Cullen’ sign – umbilical
    • Grey Turner’s sign – flank
    • Fox’s sign – thigh (parallel but inferior to inguinal ligament)

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Laboratory Studies

• Serum amylase
  • Rises within 6 hours, returns to normal in 3-5 days
  • Should not be used (sensitivity 67-83%, specificity 85-98%)
    • Short-half life (10 hours)
      • Patients presenting > 24 hours after onset can have normal amylase
    • Miss up to 20% of cases of alcohol pancreatitis
      • Due to inability of parenchyma to produce amylase
    • Miss up to 50% of cases of hypertriglyceridemia
      • Triglycerides interfere with assay
• Serum lipase
  • Sensitivity 85-100%
  • Rises 4-8 hours, peaks at 24 hours, returns to normal in 8-14 days
• LFTs
  • Evaluate for cholestatic elevations (ALP, bilirubin, GGT)
• BMP
  • Need glucose, BUN, and calcium for some of the risk calculators
• CBC
  • Leukocytosis often is present and helps grade severity
  • May show hemoconcentration due to volume depletion

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Imaging Studies

• Ultrasound
  • Often the quickest and easiest study to obtain in the ED
  • Can evaluate gallbladder pathology, stones, and peripancreatic fluid
  • Ileus can obscure imaging due to gas overlying the pancreas

• CT
  • Better detail and can evaluate more structures

• MRI
  • Higher sensitivity in early disease
  • Longer to obtain

• Revised Atlanta Criteria
  • Six CT morphological features
  • Interstitial edema
    • Parenchymal enhancement by IV contrast
  • Necrotizing findings
    • Lack of parenchymal enhancement
    • Peripancreatic fluid collection or walled-off necrosis
  • Acute peripancreatic fluid collection
    • Homogenous fluid collection
    • Confined to normal peripancreatic fascial planes
    • No definable encapsulating wall
    • Adjacent to pancreas (no intrapancreatic extension)
  • Pancreatic pseudocyst
    • Well-circumscribed, well-defined wall with homogenous fluid density
    • No non-liquid component
  • Acute necrotic collection
    • Heterogenous with non-liquid density of varying degrees
    • No definable wall
    • Intra-, or extra-pancreatic in location
  • Walled-off necrosis
    • Heterogenous with liquid and non-liquid densities
    • Well-defined wall that is completely encapsulated
    • Intra-, or extra-pancreatic in location

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Diagnosis

• Need 2 of the following 3 criteria:
  • Acute onset of persistent, severe, epigastric pain
  • Elevation of amylase or lipase > 3x ULN
  • Radiographic findings on imaging

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Classification of Severity

• Mild
  • Absence of organ failure or local/systemic complications
• Moderately severe
  • Transient organ failure (resolves with 48 hours) and/or systemic complications without persistent organ failure
• Severe
  • Persistent organ failure

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Prognosis Predictor Scoring Systems

• Ranson’s Criteria

• BISAP Score
  • 0-2 points – low mortality
  • 3-5 points – high mortality

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Management

• Patients with mild pancreatitis can be admitted to floor/wards
• Patients with moderately severe or severe should be admitted to ICU
• Fluid resuscitation
  • 5-10 mL/kg/hour with crystalloid
    • Careful, using LR in patients with hypercalcemic induced pancreatitis
  • Bolus 20 ml/kg over 30 minutes if hypotensive/tachycardic
  • Adjust using goal-directed metrics even 6 hours for first 24 hours-48 hours
    • BUN, H/H, MAP (65-85 mmHg), HR (< 120bpm), UOP (>0.5 mL/kg/hr)
• Pain control
  • Opioids are safe and PCA can work well
    • Fentanyl has better safety profile
      • 20-50 mcg with 10-min lockout
• Nutrition
  • Can reintroduce within 24 hours if no nausea, vomiting, and decreasing pain and inflammatory markers
    • Start with low-residue, low fat, soft diet and advance as tolerated
  • Supplemental nutrition generally needed for moderately severe and severe cases, or if unable to tolerate oral nutrition within 5 days
    • Enteral > parental with placement of jejunal feeding tube beyond the ligament of Treitz
      • Helps prevent bacterial translocation
    • Parenteral is indicated if nutritional goals are not achieved with 48-72 hours due to pain or intolerance
    • Consult your hospital nutritional team and/or dietician for help
• Antibiotics
  • No evidence to support prophylactic antibiotics
    • Most infected necroses will occur late in clinical course (5-10 days after admission)
• Treat underlying causes
  • Gallstone pancreatitis
    • ERCP should be performed within 24 hours of admission
    • Cholecystectomy should be performed within 7 days and often during same hospitalization
  • Hypertriglyceridemia
    • Therapeutic plasma exchange and insulin therapy

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Complications

• Necrosis
• Pseudocyst
• Splanchnic venous thrombosis

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References

1. Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013; 144(6):1252-61. [PDF]
2. Conwell DL, Banks PA, Greenberger NJ. Acute and Chronic Pancreatitis. In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 20e. McGraw-Hill;
3. Mechanisms of alcoholic pancreatitis. Proceedings of a conference. Chicago, Illinois, USA, November 2002. Pancreas. 2003; 27(4):281-355. [pubmed]
4. Nawaz H, Koutroumpakis E, Easler J, et al. Elevated serum triglycerides are independently associated with persistent organ failure in acute pancreatitis. Am J Gastroenterol. 2015; 110(10):1497-503. [pubmed]
5. Scherer J, Singh VP, Pitchumoni CS, Yadav D. Issues in hypertriglyceridemic pancreatitis: an update. J Clin Gastroenterol. 2014; 48(3):195-203. [PDF]
6. Kahaleh M, Freeman M. Prevention and management of post-endoscopic retrograde cholangiopancreatography complications. Clin Endosc. 2012; 45(3):305-12. [PDF]
7. Lankisch PG, Dröge M, Gottesleben F. Drug induced acute pancreatitis: incidence and severity. Gut. 1995; 37(4):565-7. [PDF]
8. Forsmark CE, Swaroop Vege S, Wilcox CM. Acute Pancreatitis N Engl J Med. 2016; 375(20):1972-1981.
9. Yadav D, Agarwal N, Pitchumoni CS. A critical evaluation of laboratory tests in acute pancreatitis. Am J Gastroenterol. 2002; 97(6):1309-18. [pubmed]
10. Wu BU, Johannes RS, Sun X, Tabak Y, Conwell DL, Banks PA. The early prediction of mortality in acute pancreatitis: a large population-based study. Gut. 2008; 57(12):1698-703. [pubmed]
11. Vege SS, DiMagno MJ, Forsmark CE, Martel M, Barkun AN. Initial Medical Treatment of Acute Pancreatitis: American Gastroenterological Association Institute Technical Review. Gastroenterology. 2018; 154(4):1103-1139. [pubmed]
12. Basurto Ona X, Rigau Comas D, Urrútia G. Opioids for acute pancreatitis pain. Cochrane Database Syst Rev. 2013; [pubmed]
13. Casaer MP, Mesotten D, Hermans G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011; 365(6):506-17. [pubmed]
14. Kutsogiannis J, Alberda C, Gramlich L, et al. Early use of supplemental parenteral nutrition in critically ill patients: results of an international multicenter observational study. Crit Care Med. 2011; 39(12):2691-9. [pubmed]
15. Aboulian A, Chan T, Yaghoubian A, et al. Early cholecystectomy safely decreases hospital stay in patients with mild gallstone pancreatitis: a randomized prospective study. Ann Surg. 2010; 251(4):615-9. [pubmed]
16. Uhl W, Müller CA, Krähenbühl L, Schmid SW, Schölzel S, Büchler MW. Acute gallstone pancreatitis: timing of laparoscopic cholecystectomy in mild and severe disease. Surg Endosc. 1999; 13(11):1070-6. [pubmed]
17. Ipe TS, Pham HP, Williams LA 3rd. Critical updates in the 7 edition of the American Society for Apheresis guidelines. J Clin Apher. 2018; 33(1):78-94. [pubmed]

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Question

47yo man presents to the emergency department after an episode of hematemesis at the end of a 2 day alcoholic binge. He reports drinking 1-3 handles of vodka over the weekend after his 14 consecutive day, third shift schedule every month at the local manufacturing plant. He reports moderate central chest pain, but denies shortness of breath. Vitals are BP-110/82 mmHg, HR-112, RR-14, O2-98%, and temp-99.2o. Physical exam is unremarkable, hemoccult is negative, and labs are below.

1. What are the three (3) main differentials you need to consider?
2. What is the most likely diagnosis based on exam and labs?

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Answer

1. Given the history and risk factors, the top three differentials you need to consider are variceal bleed, Mallory-Weiss tear, and Boerhaave’s syndrome.
2. The most likely of these is Mallory-Weiss tear. The unremarkable physical exam points away from Boerhaave’s as patients most commonly present with mediastinitis and, in some instances, sepsis. Other physical examination findings of Boerhaave’s include subcutaneous emphysema of the neck with crepitus and Hamman’s sign of medisatinal crunch on auscultation. Varices can self-tamponade after an acute bleed, but given the patient’s hemodynamic status being stable with a normal H/H and negative hemoccult also move this down the differential list.

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Question

47yo man presents to the emergency department after an episode of hematemesis at the end of a 2 day alcoholic binge. He reports drinking 1-3 handles of vodka over the weekend after his 14 consecutive day, third shift schedule every month at the local manufacturing plant. He reports moderate central chest pain, but denies shortness of breath. Vitals are BP-110/82 mmHg, HR-112, RR-14, O2-98%, and temp-99.2o. Physical exam is unremarkable, hemoccult is negative, and labs are below.

1. What are the three (3) main differentials you need to consider?
2. What is the most likely diagnosis based on exam and labs?