DSA Pancreas Disorders

What are the genetic factors that may predispose to chronic pancreatitis?

- CFTR o The pancreatic secretory trypsin inhibitory gene (PSTI, serine protease inhibitor, SPINK1) o Mutation of the cationic trypsinogen gene on chromosome 7 (serine protease 1, PRSS1) is associated with hereditary pancreatitis, transmitted as an autosomal dominant trait with variable penetrance.

What are characteristics of MEN type 2A?

2 or 3 of the following: - thyroid (medullary thyroid CA)->elevated calcitonin but low Ca) - Adrenal (pheochromocytoma)->elevate catecholamines - parathyroid (hypercalcemia and increased intact PTH) **patients may have normal Ca due to thyroid and parathyroid canceling each other out 2-5% will get Hirschsprung disease

What are characteristics of MEN type 1?

2 or more of the following: - parathyroid (hypercalcemia, increase intact PTH) - pancreas->gastrinoma or insulinoma - pituitary (acromegaly, Cushing) - thyroid - adrenal - carcinoid (rare)

When is CT guided needle aspiration of necrotizing pancreatitis performed?

3rd day-> Disclose infection (enteric organisms)- send for Gram stain and culture Requires debridement (surgical consult)

What does it mean in acute pancreatitis if CT is showing gas bubbles?

Implied infection (+/- abscess) with gas-forming organisms

What should be included in differential diagnosis for acute pancreatitis?

Intestinal perforation (especially peptic ulcer), cholecystitis, acute intestinal obstruction, mesenteric vascular occlusion, renal colic, inferior myocardial infarction, aortic dissection, connective tissue disorders, pneumonia, and diabetic ketoacidosis, leaking aortic aneurysm

What does PMH show for acute pancreatitis?

PMH: previous episodes? often related to alcohol intake. o May be a history of alcohol intake or o A heavy meal immediately preceding the attack

What are the general characteristics of pancreatic adenocarcinoma?

Painless jaundice, N/V, Fatigue, Weight loss, Steatorrhea If there is pain it is typically mid-epigastric pain that radiates to the back, hurts the most at night (lying flat on back) Trousseau sign of Malignancy (need to differentiate this from the other Trousseau sign for hypocalcemia) Courvoisier Sign Head and neck of pancreas most common place increase in CA19-9 and CEA

What causes cellular injury in acute pancreatitis?

o Activation of protein kinases and Inflammatory mediators o Activation of digestive enzymes in the pancreas Trypsinogen to trypsin results in autodigestion of the pancreas and peri-pancreatic tissues

What precipating factors should be eliminated with acute pancreatitis?

o Alcoholic pancreatitis->Abstinence o Gallstone pancreatitis->Once recovering Timely Lap Cholecystectomy o Recurrent pancreatitis from Pancreas divisum->Sphincterotomy or stent Sphincter of Oddi dysfunction Sphincterotomy o Hypertriglyceridemia pancreatitis (Serum triglycerides >1000 mg/dL) (in these patients their amylase might be normal) Initial therapy: insulin, heparin, plasmapheresis Cont. tx- outpatient: manage diabetes mellitus if it co-exists, administer lipid-lowering agents, weight loss, avoidance of drugs that elevate lipid levels o Post ERCP prophylaxis (reduce risk in those with high risk) NSAIDs, indomethacin rectally and aggressive hydration with IVF using lactated ringers Reduced by administration of somatostatin, octreotide ((more studies needed) Placement of a stent across pancreatic duct or orifice

What is the etiology behind chronic pancreatitis?

o Alcoholism is most frequent cause of clinically apparent chronic pancreatitis o The pathogenesis of chronic pancreatitis may be explained by The SAPE (sentinel acute pancreatitis event) hypothesis by which the first (sentinel) acute pancreatitis event initiates an inflammatory process that results in injury and later fibrosis ("necrosis-fibrosis"). o A mnemonic for the predisposing factors of chronic pancreatitis is TIGAR-O

How is MEN associated with GI?

o Associated with MEN 1 o Pancreatic Neuroendocrine (Islet Cell) Tumors Insulinoma Hypersecretion of insulin Hypoglycemia; associated with MEN 1 high insulin and creative protein during hypoglycemia Gastrinoma (Z-E Syndrome) Nonbeta islet cell tumors Hypersecretion of gastrin Leads to multiple peptic ulcers, refractory to standard tx Most commonly found in duodenum 2 nd most common spot is the pancreas- especially in MEN 1

What is chronic pancreatitis?

o Characterized by irreversible damage to the pancreas. o Self-perpetuating disease characterized by o chronic pain or recurrent episodes of acute pancreatitis o and ultimately by pancreatic exocrine or endocrine insufficiency (sooner in alcoholic pancreatitis than in other types). Malabsorption- exocrine insufficiency Diabetes mellitus - endocrine insufficiency o Over 80% of adults develop diabetes mellitus within 25 years after the clinical onset of chronic pancreatitis.

What is associated with an increased mortality rate in acute pancreatitis?

o Hypoalbuminemia and marked elevations of serum lactic dehydrogenase (LDH) are associated with an increased mortality rate.

What is the hypocalcemia in a cute pancreatitis caused by?

o Hypocalcemia Saponification = "making into soap" In acute pancreatitis o Interaction of cations with free fatty acids released by the action of activated lipase on triglycerides in fat cells low blood calcium. <7.0 with a normal albumin = tetany and poor prognosis

What is seen in Labs for acute pancreatitis?

o Increase lipase (more accurate than amylase, therefore the preferred test) o 3 x Upper Limit of Normal o Increase amylase (sometimes may be normal in pancreatitis from ↑TG) o Large elevations (>3 × normal) virtually assure the diagnosis if salivary gland disease and intestinal perforation/infarction are excluded. However, normal serum amylase does not exclude the diagnosis of acute pancreatitis, and the degree of elevation does not predict severity of pancreatitis. Amylase levels typically return to normal in 3-7 days o Proteinuria o Granular casts in urine o Glycosuria o Leukocytosis o Hyperglycemia o Hyperbilirubinemia o ↑ Alkaline phosphatase o Abnormal coagulation studies o ↑ BUN o Elevated creatinine (Acute kidney insufficiency (AKI) usually prerenal) >1.8 at 48 hours indicative of pancreas necrosis o Elevated ALT >150 then think biliary etiology (stone?) o Hypocalcemia. - hypertriglyceridemia (greater than 1000) - elevated Hct (>44%->pancreatic necrosis) - increase CRP - hypoxemia (25%)

What are the symptoms of acute pancreatitis?

o Nausea, vomiting, sweating, weakness, abdominal tenderness and distention and fever. Can vary from mild abdominal pain to shock Common symptoms: (1) steady, boring pain in the epigastric and periumbilical region may radiate to the back, chest, flanks, and lower abdomen; severe and often made worse by walking and lying supine and better by sitting and leaning forward (2) nausea, vomiting, weakness, abdominal distention.

What are nonmedication ways to treat pain in chronic pancreatitis?

o No consistent benefit of enzyme therapy at reducing pain in chronic pancreatitis o Surgery with ductal decompression may control pain if there is a large-duct disease. o Subtotal pancreatectomy may also control pain but at the cost of exocrine insufficiency and diabetes.

What are the risk factors for pancreatic adenocarcinoma?

o Smoking o Obesity o Male o African American o >65 yo o Diabetes Mellitus o Chronic pancreatitis o Liver cirrhosis (alcohol) o Family history

What is necrotizing pancreatitis?

o fever, leukocytosis, and, in some cases, shock and is associated with organ failure (eg, gastrointestinal bleeding, respiratory failure, acute kidney injury) o Because infected pancreatic necrosis is often an indication for debridement, fine-needle aspiration of necrotic tissue under CT guidance should be performed (if necessary, repeatedly) for Gram stain and culture.

What does chronic pancreatitis need to be distinguished from?

pancreatic carcinoma; may require radiographically guided biopsy.

What are examples of fluid collections in acute pancreatitis?

pleural effusion and ascites (usually occurs after recovery) Gradual increase in abdominal girth and persistent elevation of serum amylase in the absence of frank abdominal pain Marked elevation in ascitic protein (greater than 3g/dL) and amylase (>1000units/L) Because of disruption of the pancreatic duct or drainage of a pseudocyst into the peritoneal cavity

What is the most important treatment for acute pancreatitis?

sage, aggressive IV fluid resuscitation the importance of aggressive intravenous hydration targeted to result in adequate urinary output, stabilization of blood pressure and heart rate, restoration of central venous pressure

HAPS

Harmless acute pancreatitis score predicts non-severe course with 96% accuracy - no abdominal tenderness, rebound or gaurding - normal hematocrit - normal serum creatine level

What is the treatment for chronic pancreatitis?

Abstain from alcohol use Aimed at controlling pain and malabsorption. - insulin to control serum glucose - steroids for autoimmune - endoscopic therapy or surgery

What can be seen in unenhanced CT for acute pancreatitis?

CT can confirm the clinical impression of acute pancreatitis. It can also be helpful in evaluating the complications of acute pancreatitis. Useful for demonstrating enlarged pancreas when diagnosis is uncertain Differentiating pancreatitis from other possible "intra-abdominal catastrophes" Acutely perforated duodenal ulcer, acute intestinal obstruction, leading aortic aneurysm, acute mesenteric ischemia Providing an initial assessment of prognosis Often unnecessary early in the course

What are the complications associated with chronic pancreatitis?

Chronic abdominal pain, gastroparesis, malabsorption/maldigestion, impaired glucose tolerance (Brittle diabetes mellitus). Nondiabetic retinopathy due to vitamin A and/or zinc deficiency. GI bleeding, icterus, effusions, subcutaneous fat necrosis, and metabolic bone disease. Opioid/Narcotic addiction common Pancreatic pseudocyst or abscess Bile duct stricture, steatorrhea, malnutrition, osteoporosis, and peptic ulcer Pancreatic cancer develops in 4% of patients after 20 years; the risk may relate to tobacco and alcohol use. In patients with hereditary pancreatitis, the risk of pancreatic cancer rises after age 50 years and reaches 19% by age 70 years

What are the symptoms and signs of chronic pancreatitis?

Chronic or intermittent epigastric pain, steatorrhea, weight loss, abnormal pancreatic imaging Anorexia, nausea, vomiting, constipation, flatulence, and malabsorption, weight loss are common. Pain is cardinal symptom. Physical examination often unremarkable. o Persistent or recurrent episodes of epigastric and left upper quadrant pain are typical. o The pain results in part from impaired inhibitory pain modulation by the central nervous system. o During attacks, tenderness over the pancreas, mild muscle guarding, and ileus may be noted. Attacks may last only a few hours or as long as 2 weeks; pain may eventually be almost continuous. Steatorrhea (as indicated by bulky, foul, fatty stools) may occur late

What is seen with rapid-bolus IV contrast CT for acute pancreatitis?

Following aggressive volume resuscitation is of particular value after 3 days of severe acute pancreatitis Identifying areas and degree of pancreatic necrosis IV contrast may increase complications of pancreatitis and of AKI Should be avoided when serum Cr > 1.5 mg/dL

What are rare complications of acute pancreatitis?

Hemorrhage (erosion of blood vessel to form a pseudoaneurysm) Colonic necrosis Portosplenomesenteric venous thrombosis Chronic pancreatitis in 10% Permanent DM and exocrine pancreatic insufficiency

What is seen for endoscopic ultrasound for acute pancreatitis?

Identifying occult biliary disease Small stones, sludge, microlithiasis Present in a majority of patients (Idiopathic cause) Indicated in patients over 40 to exclude malignancy Drain a pseudocyst

What are the different labs used for chronic pancreatitis/pancreatic function tests?

No specific laboratory test for chronic pancreatitis. Serum amylase and lipase levels are often normal. Serum bilirubin and alkaline phosphatase may be elevated (if there is compression of bile duct) The fecal elastase-1 and small-bowel biopsy are useful in the evaluation of pts with suspected pancreatic steatorrhea (malabsorption/insufficiency). Impaired glucose tolerance is present in >50% of pts. o glycosuria Secretin stimulation test is a relatively sensitive test for pancreatic exocrine deficiency o Becomes abnormal when ≥60% of the pancreatic exocrine function has been lost.

What is the prognosis for chronic pancreatitis?

Often leads to disability and reduced life expectancy; pancreatic cancer is the main cause of death. The quality of life is poorer in patients with constant pain than in those with intermittent pain

What is found in ultrasound for acute pancreatitis?

Often not helpful because of intervening bowel gas May identify gallstones in the gallbladder, pseudocysts, mass lesions, or edema or enlargement of the pancreas

When is perfusion CT (PCT) used for acute pancreatitis?

Specialized contrasted CT Specifically focus on an organ and its perfusion (in this case the pancreas) Lower dose contrast injected at a higher rate Performed on day 3 looking for areas of ischemia and predict development of necrosis Presence of fluid collection in the pancreas correlates with an increased mortality rate

What are the preferred agents for pain for chronic pancreatitis?

acetaminophen, nonsteroidal anti-inflammatory drugs, and tramadol along with pain-modifying agents such as tricyclic antidepressants, selective serotonin reuptake inhibitors, and gabapentin or pregabalin. o Pregabalin can improve pain in chronic pancreatitis and lower pain medication requirement

What are pancreatic abscess?

also referred to as infected or suppurative pseudocyst suppurative process characterized by o rising fever, leukocytosis, and localized tenderness and an epigastric mass usually 6 or more weeks into the course of acute pancreatitis. o associated with a left-sided pleural effusion or an enlarging spleen secondary to splenic vein thrombosis o Mortality low after drainage

What is ileus?

fluid-filled loops of bowel

What can cause intravascular volume depletion in acute pancreatitis?

secondary to leakage of fluids in the pancreatic bed 3 rd spacing prerenal azotemia or acute tubular necrosis without overt shock

What is typically found on PE for acute pancreatitis?

(1) low-grade fever, tachycardia, hypotension (even shock); (2) erythematous skin nodules due to subcutaneous fat necrosis; (3) basilar rales, pleural effusion (often on the left- fluid shifts); (edema-3 rd spacing) (4) abdominal tenderness and rigidity, diminished bowel sounds (absent if there is an associated ileus), palpable upper abdominal mass; (5) Cullen's sign: blue-purple discoloration in the periumbilical area due to hemoperitoneum; (6) (Grey) Turner's sign: blue-red-purple or green-brown discoloration of the flanks due to tissue catabolism of hemoglobin.

What other conditions can cause an elevated amylase?

(Lipase could be elevated in some of these, but is still considered more accurate of a measurement for pancreatic source.) High intestinal obstruction Gastroenteritis Mumps (not involving pancreas- salivary amylase) Ectopic pregnancy Administration of opioids After abdominal surgery

When is ERCP used in acute pancreatitis?

(REMEMBER that one of the possible complications of ERCP is pancreatitis!) So When Do We Consider doing it? Not indicated after a first attack Unless there is associated cholangitis, jaundice, or bile duct stone known to be present In selected patients, aspiration of bile for crystal analysis may confirm suspicion of microlithiasis Manometry of pancreatic duct sphincter may detect sphincter of Oddi dysfunction Recurrent pancreatitis EUS or MRCP should be considered, especially after repeated attacks of idiopathic acute pancreatitis (short for endoscopic retrograde cholangiopancreatography) is a procedure used to diagnose diseases of the gallbladder, biliary system, pancreas, and liver. ... In addition, ERCP can be used to treat problems in these parts of the digestive system

What is a sentinel loop?

(a segment of air-filled small intestine most commonly in the left upper quadrant)

What is seen in plain radiography for acute pancreatitis?

(x-ray) Can be abnormal but are not specific for pancreatitis and are infrequently used. Sentinel loop, Colon Cut-off Sign, Calcified gallstones, Focal linear atelectasis of the lower lobe of the lungs with or without pleural effusion A "sentinel loop" (a segment of air-filled small intestine most commonly in the left upper quadrant) The "colon cutoff sign"—a gas-filled segment of transverse colon abruptly ending at the area of pancreatic inflammation (absence of gas distal to splenic flexure caused by colonic spasm from pancreatic inflammation)—or focal linear atelectasis of the lower lobe of the lungs with or without pleural effusion.

What is the diagnosis of acute pancreatitis based on?

**The diagnosis is established by two of the following three criteria: o (1) typical abdominal pain in the epigastrium that may radiate to the back, o (2) threefold or greater elevation in serum lipase and/or amylase, and o (3) confirmatory findings of acute pancreatitis on cross-sectional abdominal imaging

What are characteristics of MEN type 2B?

- Marfanoid body habitus - medullary thyroid cancer (elevated calcitonin) - pheochromocytoma (elevate catecholamines) - neuromas->occur on lips, tongues, mouth, eyelids - freq a new gene mutation (no family hx)

What are complications of severe acute pancreatitis?

- Necrotizing pancreatitis - multisystem organ failure - intravascular volume depletion - ileus - fluid collections - necrosis (pseudocyst) - ARDS - Pancreatic abscess

What are protective factors related to acute pancreatitis?

- eating veggies - use of statins

What is the tx for acute pancreatitis?

- severity assessed to see if ICU care is required (hemodynamic monitoring, utilize severity assessment) - IV fluid resuscitation - no oral alimentation and parental analgesics for abdominal pain - eliminate precipitating factors - Calcium glutinate (if tetany present) - infusion of fresh frozen or serum albumin) - may need vasopressors if shock persists after adequate volume replacement

What are the risk factors for acute pancreatitis?

- smoking - high dietary glycemic load - abdominal adiposity - increase age and obesity (increases changes of more severe course)

What is the clinical presentation for pancreatic cancer?

- vague diffuse pain in epigastrium and LUQ (if tail involved) - diarrhea and wt loss - depression - painless jaundice - palpable gallbladder (Courvoisier sign)

What is the revised Atlanta class of severity of acute pancreatitis?

1. Mild: absence of organ failure and local pancreatic necrosis or fluid collections or systemic complications 2. Moderate: disease is the presence of transient (under 48 hrs) organ failure or local or systemic complications or both 3. SevereL presence of persistent (48 hrs+) organ failure

What are the different assessments for determining severity of acute pancreatitis?

1. Ranson Criteria (GA-LAW and HOBBS) 2. APACHE II (Acute Physiology and Chronic Health Eval) 3. Bedside Index for severity in acute pancreatitis (BISAP) 4. HAPS (harmless acute pancreatitis score) 5. Revised Atlanta class (mild, moderate, severe) 6. CT Gated of Severity index 7. presence of SIRS and high BUN with rise in BUN in first 24 hrs of hospitalization 8. early rise in serum levels of neutrophil gelatinase-associated lipocalin=severe acute pancreatitis 9. sequential organ failure assessment (SOFA) 10. Modified Marshal Scoring System

APACHE II

Acute Physiology and Chronic Health Evaluation II not just for pancreatitis->also used as ICU scoring system that predicts hospital mortality >8=higher mortality

What are characteristics of Multiple endocrine neoplasia syndrome (MEN) ?

Autosomal dominant Rare Endocrine glands - benign or malignant Three patterns o Type 1 o Type 2A o Type 2B

BISAP

Bedside index of severity of acute pancreatitis score=(BUN>25, impaired mental status, SIRS, Age>60 and pleural effusion (before onset of organ failure) - scale: 0-5 mortality<1% for BISAP of 0-1, up to 27% for score of 5

What are the 2 functions of the pancreas?

Endocrine Exocrine (digestion)

What is the imaging related to chronic pancreatitis?

Plain films of the abdomen reveal pancreatic calcifications CT scan is the imaging modality of choice followed by MRI, endoscopic ultrasound, and pancreas function testing.

What can pregabalin do?

Pregabalin can improve pain in chronic pancreatitis and lower pain medication requirement

When should a pancreatic pseudocyst be drained?

Pseudocysts that are >5 cm in diameter and persist for >6 weeks should be considered for drainage

What should be considered with any change in clinical course to monitor complications of acute pancreatitis?

Repeated CT or MRI imaging

When should MRCP be considered in acute pancreatitis?

Should be considered, especially after repeated attacks of idiopathic ***not thereupetic

What imaging is performed for acute pancreatitis?

X-ray ultrasound unenhanced CT - rapid bolus IV contrast CT - MRI - perfusion CT (PCT) - CT guided needle aspiration - CT showing gas bubles - endoscopic ultrasound EUS

What is ARDS?

acute respiratory distress syndrome->cardiac dysfunction may be superimposed. o It usually occurs 3-7 days after the onset of pancreatitis in patients who have required large volumes of crystalloid fluid and colloid fluids to maintain blood pressure and urinary output. o Most patients with ARDS require intubation, mechanical ventilation, and supplemental O2.

What is MRI used for in acute pancreatitis?

alternative to CT

How is malabsorption managed in chronic pancreatitis?

managed with a low-fat diet and pancreatic enzyme replacement. Because pancreatic enzymes are inactivated by acid, agents that reduce acid production (e.g., omeprazole or sodium bicarbonate) may improve their efficacy (but should not be given with enteric-coated preparations).

Which patients may need plasma or serum albumin?

may be necessary in patients with coagulopathy or hypoalbuminemia. o With colloid solutions (these are examples of colloid fluids), the risk of ARDS may be increased o (Crystalloid fluids are fluids such as normal saline or lactated ringers)

What is the etiology behind acute pancreatitis?

cholelithiasis and alcohol

What is independently associate with increased mortality?

greater rise in BUN the greater the mortality rate

What is autoimmune pancreatitis associated with?

hypergammaglobulinemia (IgG4) often with autoantibodies and other autoimmune diseases Is responsive to corticosteroids.

When is endoscopic therapy or surgery indicated in chronic pancreatitis?

to treat underlying biliary tract disease, ensure free flow of bile into the duodenum, drain persistent pseudocysts, treat other complications, eliminate obstruction of the pancreatic duct, attempt to relieve pain, or exclude pancreatic cancer.

What is the pathologic spectrum of acute pancreatitis?

varies from o Interstitial pancreatitis, which is usually a mild and self-limited disorder to o Necrotizing pancreatitis, in which the degree of necrosis may correlate with the severity of the attack and its systemic manifestations.

What is pancreatic pseudocyst?

walled-off necrosis o are characterized by encapsulation, have high amylase content o develop over 1-4 weeks in 15% of pts. o Abdominal pain is the usual complaint, and a tender upper abdominal mass o Can be detected by abdominal ultrasound or CT. o In pts who are stable and uncomplicated, treatment is supportive o Pseudocysts that are >5 cm in diameter and persist for >6 weeks should be considered for drainage. o In pts with an expanding pseudocyst or one complicated by hemorrhage, rupture, or abscess, surgery should be performed. o Infection needs debridement (high mortality) o Pancreatic debridement (necrosectomy) should be considered for definitive management of infected necrosis o Can show up anywhere along anatomic planes (usually adjacent)

What is the colon cutoff sign?

—a gas-filled segment of transverse colon abruptly ending at the area of pancreatic inflammation (absence of gas distal to splenic flexure caused by colonic spasm from pancreatic inflammation)—or focal linear atelectasis of the lower lobe of the lungs with or without pleural effusion

What should be given in severe pancreatitis?

—particularly necrotizing pancreatitis - there may be considerable leakage of fluids o necessitating large amounts of intravenous fluids (eg, 500-1000 mL/h for several hours, then 250-300 mL/h) to maintain intravascular volume o Risk factors for high levels of fluid sequestration [3rd spacing/edema] include: younger age, alcohol etiology, higher hematocrit value, higher serum glucose, and systemic inflammatory response syndrome in the first 48 hours of hospital admission.