Pancreatic and Biliary Disease: An

Overview

Tory Davis PA-C

Table of Contents

Pancreatic disease– Acute pancreatitis– Chronic pancreatitis

Gallbladder disease– Cholelithiasis– Cholecystitis

Acute Pancreatitis Inflammation of pancreas (+/-adjacent

tissue) – caused by release of activated pancreatic

enzymes within gland (autodigestion) Several possible etiologies Range from mild (abd pain, vomiting-

inflammation confined to gland, 5% mortality) to severe (really bad, maybe dead: pancreatic necrosis, systemic inflammatory process, shock, multi-organ failure- up to 50% mortality)

What’s happening Pancreatic enzymes (trypsin,

phospholipase A2, elastase) get activated within the gland

Cause tissue damage directly AND Activate complement and inflammatory

cascades, producing cytokines inflammation, edema, tissue necrosis

Then what? Cytokines and enzymes in peritoneum

cause chemical burns, fluid third-spacing

In systemic circ systemic inflammatory response capillary permeability and vascular tone– acute respiratory distress, renal failure

Who’s responsible for this mess?

EtOH- 100 g/d x 3-5 yrs (lots)pancreatic enzyme proteins to precipitate in small ductulesobstructionpremature activation of enzymes

Biliary/structural- gallstone in Sphincter of Oddi ductal pressures

Etiology 80% caused by alcohol or biliary tract

disease/structural disorders– Stones– ERCP (dx imaging study)– Trauma– Ischemia– Vasculitis– Pancreas divisum – predisposes for

pancreatitis

Etiology 20% caused by “other”

– Drugs: ACE-I, sulfa, NSAIDs– Infectious: CMV, mumps, Coxsackie B– Inherited: CF, other gene mutations– Metabolic: hypertrigs, hypercalcemia,

hyperparathyroid– Other: pregnancy, embolism

Causes of Acute Pancreatitis: GET SMASH'D

Gallstones (most common reason for acute pancreatitis with amylase >1000 units/L)

Ethanol (alcohol) Trauma (usually blunt abdominal injury) Steroids Mumps Autoimmune Scorpion bites (akin to zebra bites in Maine) Hyperlipidemia (particularly

hypertriglyceridemia) Drugs (ACE-I, sulfa)

Acute Pancreatitis S&S Steady, boring deep epigastric pain

– Radiates to the back in 50% Sudden onset with gallstone pancreatitis,

gradual sx increase over days with EtOH Nausea and vomiting common Alleviated by sitting upright, lean forward Aggravated by vigorous movement, deep

inspiration, coughing Weakness, anxiety, diaphoresis

Physical Exam Acutely ill appearing Febrile Mild jaundice possible Tachycardic, diaphoretic, pale Tachypneic with shallow respirations diaphragmatic excursion

– Why? Don’t want to breath Postural hypotension Blunted sensorium

Exam Marked upper and mild lower abd

tenderness with guarding Mild-moderate upper abd rigidity Rectum nontender, neg FOBT Hypoactive BS, maybe absent (ileus) Evidence of extravasation of hemorrhagic

exudate– Grey Turner’s sign: flank ecchymosis– Cullen’s sign: umbilical ecchymosis

Work-up Lipase more specific, elevated up to 14

days Amylase elevate early, recedes 3-5 days

Non-specific to pancreas

CMP- – elevated glucose, Ca– elevated alk phos and bilirubin indicating

obstruction LDH- elevated from tissue necrosis

Work-up CBC with diff-

– WBC up to 12-20– Hct 50-55% (indicating 3rd spacing)

EKG- r/o MI U/S to image biliary tree

– Start here - it’s faster and cheaper– Stones easily observable and fixable

CT to image pancreas itself– Necrosis, vascular involvement, mass

Ddx Perforated ulcer

(gastric, duodenal) Mesenteric

infarction Strangulating

intestinal obstruction

Dissecting aneurysm

Biliary colic Appendicitis Inferior wall MI Splenic hematoma Abd muscle

hematoma

Ranson’s Criteria for Pancreatitis Mortality

Determine and document at admission – Age >55– Glucose>200– Serum LDH>350– AST>250– WBC>16,000

If 3 or more present at admission, severe course predicted with 60-80% sensitivity

Ranson’s Criteria: Part 2 Development of these in 1st 48h

heralds worsening prognosis– HCT > 10%– BUN > 5mg/dL– Ca <8mg/dL– PaO2 <60 mmHg– Fluid sequestration >6L– Base deficit over 4 meq/L

Ranson’s CriteriaMortality proportional to # of criteria

Download to your PDA for IM rotations…

Number of Criteria

0-23-45-67-8

Mortality

1%

16%

40%

100%

Treatment Adequate fluids- up to 6-8 L/day IV fluid

with lytes- dilute enzymes, reduce inflammatory markers

NPO until acute inflammation subsides– To avoid stimulation or release of enzymes– Until pain/tenderness resolved, nl labs, appetite

present, feels better- may take days to weeks– NG tube for pts with ileus, abd distention,

vomiting

Acute pancreatitis Tx Pain relief- parenteral opioids

– such as demerol Anti-emetics H2 blockers and/or PPI

– why? Stop stomach acid production (doesn’t stimulate pancreas)

IVF Surgical consult for severe pancreatitis

Treatment ICU admission if oliguric, hypotensive,

Ranson’s 3, or pancreatic necrosis by CT >30%

Humidified O2 if hypoxic Treat heart failure, renal failure,

hyperglycemia, hypomagnesemia etc Abx (imipemem x 1 wk)

Tx If gallstone pancreatitis: 80% will pass stone spontaneously within

24h If not…ERCP w/ sphincterotomy and stone

removal

If they DO pass the stone spontaneously, may elect lap cholecystectomy later

Oh and.. After 5-7d, necrotic tissue can become

infected If pt initially stabilizes, then

deteriorates OR if pt appears toxic, w/ high temp, high WBCs, suspect infection with enteric bacteria

100% mortality unless aggressive tx with surgical debridement or drainage

Other complications Intravascular volume depletion, shock Prerenal azotemia

– May require peritoneal or hemodialysis ARDS- acute respiratory distress

syndrome Pancreatic abscess- needs drainage GI bleed

Chronic Pancreatitis

Persistent inflammation of pancreas permanent structural damage decrease in endocrine and exocrine functions

Chronic Pancreatitis In US, 70-80% from alcohol, 15-25%

idiopathic Mechanism: ductal obstruction from

protein plugs– Chronic obstructionchronic and

persistent inflammation fibrosis and alternating ductal stricture and dilation

– Neuronal sheath hypertrophy and peri-neural inflamchronic pain

– DM in 20-30% in 10-15 yrs due to loss of endocrine function

S&S Episodic abd pain in 85-90%

– Severe pain, lasts hours to days– Episodes subside in 6-10 years, after acinar cells

destroyed Steatorrhea when lipase and protease are

<10% of normal– Greasy stools, oil droplet leakage– Sort of like eating a bag of Olestra WOW! Chips

Weight loss

Dx Chronic Pancreatitis Difficult to dx Amylase/lipase are normal early Typical alcohol hx helps X-ray show calcification in 30%- but not

until late in disease process Without typical hx, must r/o malignancy with

abd CT– If nl, ERCP, endoscopic US, secretin pancreatic

function testing

Tx

Similar to acute pancreatitis Acutely: NPO, fluids, opioids Long term: EtOH cessation, low-fat

diet to pancreatic enzyme secretion Often these don’t help; may need

opioids, with real concern for addiction

Surgery (pancreatic resection) for pts abstinent from EtOH who can manage DM

Drugs Tx steatorrhea with pancreatic

supplements– 30,000 units of lipase given before,

during, after meals acid-stimulated release of secretin

– H2 blocker (ranitidine150 mg BID– PPI (omeprazole 20-60 mg qday)– Sodium bicarb 650 mg ac and pc

Gallbladder

Anatomy 101 Anatomy of Biliary Tree

– R & L hepatic ducts from liver form Common Hepatic Duct

– Joins Cystic Duct from GB to form Common Bile Duct

– Pancreatic Duct joins at Ampulla of Vater, has Sphincter of Oddi

– Enters duodenum at Major Duodenal Papilla

Biliary Disease Cholestasis – impairment of bile formation

or transport from metabolic, autoimmune, infectious, genetic, or toxic abnormalities

Most biliary disease is caused by gallstones– Found in 20% ♀ and 8% ♂ > 40 y.o.

Biliary sludge: thick mucoid stuff contains phospholipids, cholesterol and Ca++ crystals– Precursor to gallstones

Gallstone Formation Gallstones mostly cholesterol, bilirubin, and

Ca++ salts, plus proteins and other materials 80% of stones are cholesterol stones, 20%

are pigment stones– Cholesterol stones form when bile

supersaturated with cholesterol– Multilaminar vesicles of phospholipid and

cholesterol form nucleus of stone– Insoluble cholesterol crystals laminate onto

surface and grow within mucin gel– Polar bile proteins then fuse crystals into stones

Pigment Stones Ca++ salts of bilirubin

– Often in polymers with mucin glycoproteins, some cholesterol

About 15% of stones can be seen on X-ray, and 2/3 of these are pigment stones (more calcified)

Why these form is not well understood, but some links to infection and other processes

Etiol/Epidemiology Cholesterol stone formation factors are proportions

of cholesterol, phospholipid, and bile acids in gall bladder

Stones form when cholesterol output increased or bile acid secretion decreased or combination of both

Process enhanced by estrogen and cholesterol– Female, OCP, multiparous, over forty – Obesity; rapid weight loss and fasting– Serum cholesterol not a predictor

Cholelithiasis Presence of one or more calculi in

gallbladder In US, 20% of people >65 have stones Most disorders of biliary tract are

caused by stones 80% asymptomatic Sx and disease when stones cause

obstruction

Cholelithiasis

Consequences: – Cholecystitis– Bile tract obstruction/biliary colic– Infection (cholangitis)– Gallstone pancreatitis

Biliary colic Caused by transient cystic duct

obstruction RUQ pain, poorly localized Sudden onset, peaks in 15-30 min,

steady for 1-6h, dissipates over 30-60 min, leaving dull ache– If lasts >6h, suspect pancreatitis or

cholecystitis, not colic

Biliary Colic Intensify 30-60 minutes after eating

(why?), resolves in hours Eructation, N/V, dyspepsia, flatulence,

reflux Mild transient elev serum bili >5 Broad, scary DDx, incl PUD,

pancreatitis, cardiac syndromes, SBO, AAA, pleurisy, hepatitis, gastroenteritis, PTX

Biliary colic Pain- severe N/V, no F/C Labs normal Feels FINE between episodes Tests:

– Abd US 95% specific for stones– CT, MRI– Endoscopic US if other tests equivocal

CholelithiasisPrognosis

Asymptomatic stones get symptomatic at average rate of 2% per year– Diabetics prone to complications, so recommend

cholecystectomy even in absence of sx Symptomatic: Colic resolves spontaneously

but recurs in 20-40% of pts per year Complications: cholecystitis,

choledocholithiasis, cholangitis, gallstone pancreatitis

Cholelithiasis Treatment Elective cholecystectomy

– Open– Laparoscopic

Converts to open in 5% due to difficulty in identifying anatomy or complications

Non surgical– High risk (age, comorbidities)– Stones can be dissolved with oral bile salts

made from bear bile. $$$, lots of SEs, lifetime tx

Cholecystitis Inflammation of gallbladder Usually cystic duct obstruction by stone Stone lodges obstructionbile

stasisrelease of inflammatory enzymes Damaged mucosa secretes more fluid into

gallbladderdistension inflammatory mediatorsworse mucosal damage ischemiamore inflammation

Cholecystitis Most commonly a complication of

cholelithiasis But 5-10% are acalculous Common for pts to have hx biliary colic RUQ pain and tenderness Develops over hours +/- nausea, vomiting, fever, chills Can lead to bacterial infection, necrosis,

perforation

S&S Like biliary colic, but worse and

doesn’t resolve Vomiting R subcostal tenderness + Murphy’s sign R sided guarding Low grade fever

IF… … abd pain, fever, rigors, + rebound

tenderness- think empyema or perforation

…accompanied by jaundice, think common duct obstruction

…untreated, 10% will have local perforation, 1% free perfperitonitis

Dx and Tx Dx: US- (incl ultrasonographic Murphy’s

sign) If unequivocal, cholescintography (HIDA

scan) Check CBC, LFTs, amylase/lipase

– Expect leukocytosis with L shift, nl LFTs Tx: NPO, IV fluids, opioids, parenteral abx,

admit, cholecystectomy in next 24-48h

Cholecystitis Complications

Emphysematous cholecystitis: result of gangrene, gas-producing bacteria (usually Clostridium)

Porcelain GB: repeated inflammation causes deposition Ca++ salts in GB wall

Fistula Ileus

Choledocholithiasis Common duct stones Most passed from GB, some form in

CBD Sx of gallstones plus possible

pancreatitis Charcot’s Triad: RUQ pain, jaundice,

fever (usually with chills) ERCP - possible stent, sphincterotomy

Cholangitis Painful inflammation of biliary tree If infection occurs, then can be suppurative Ascending Cholangitis: rises to infect liver May form obstructing empyema, abscess,

gangrene, perforation fulminant liver failure, peritonitis, sepsis (death, too)

Suppurative cholangitis is life threatening - SCU admission, abx, supportive care, surgical consult

Primary Biliary Cirrhosis Inflammation & necrosis of cholangiocytes

in small and mid-size bile ducts Immunologic process Cholestatic process results in liver dz Signs/Sx of biliary obstruction

– Pruritis, RUQ pain, indigestion, xanthomas and xanthelasmas, eventual cirrhosis and liver failure

Mostly ♀ > 40 with co-morbid auto-immune disorders

Biliary Dyskinesia

Can have all sx of cholecystitis, but no stones, no sludge

Usually dysfunction at Sphincter of Oddi