GB and Pancreas disorders

10.26.2018
Bilirubin  Increased bilirubin production in elevated red cell turnover
Conjugation
 Bilirubin is insoluble in H2O
 Glucuronic acid conjugation in liver allows bilirubin to be water soluble and excreted in bile
 Unconjugated (indirect) bilirubin and conjugated (direct) can be measured
 Bilirubin is reversibly bound to albumin in blood
 When [molar] of bilirubin exceeds albumin encephalopathy can occur
 Sulfonamides, Warfarin, NSAIDs bind to albumin at the same site
 These drugs can displace bilirubin increasing risk of brain toxicity
Bile Role of Bile
 Enhances fat solubilization producing microscopic micelles – bile salt molecules that are water
soluble at one pole and fat soluble at other pole
Components of Bile
 Bile salts – cholate, chenodeoxycholate
 Phospholipids – lecithin
 Cholesterol
Enterohepatic  Albumin bilirubin complex dissociates in liver sinusoids and is taken up by hepatocytes.
Circulation Albumin stays in circulation.
 Bilirubin conjugated by liver
 Bile secreted into intrahepatic bile ducts, concentrated in
gallbladder (500-1500 cc/day) and secreted into extra-
hepatic bile ducts and then enters small intestine via
ampulla of Vater.
 Cholic acid, chenodeoxycholate absorbed in ileum
 Some converted to bile salts in colon (lithocholate,
deoxycholate)
 Bile salts reconjugated in liver and excreted in bile. 95% of
bile salts are reabsorbed in one pass. Bile salt pool is 1.5 –
3 grams and passes through liver 2-3 times per meal.
Circulation Degradation
 Terminal ileal disease – Crohn’s disease, lymphoma
 Bacterial overgrowth of gut
 Biliary fistula – i.e. cutaneous, fistula to colon, etc.
Jaundice/Cholestasis  Elevated direct and/or indirect (unconjugated) bilirubin
 May be caused by bilirubin overproduction (hemolysis)
 Impaired bilirubin conjugation
 Biliary obstruction
 Hepatic inflammation
 Key laboratory tests – Albumin, Alkaline phosphatase, GGTP (gamma-glutamyl transpeptidase)
Alanine aminotransferase, Aspartate aminotransferase, Total, Direct bilirubin
 Prothrombin time
Unconjugated Hyperbilirubinemia
 Hemolysis, dyserythropoiesis, sepsis, impaired liver uptake, certain drugs i.e. Rifampin, impaired
conjugation, neonatal, Gilbert syndrome, Crigler Najjar, Cirrhosis / hepatitis
Conjugated Hyperbilirubinemia
 Biliary extra hepatic obstruction, Common duct stone, Pancreatic cancer, Sclerosing cholangitis,
Biliary cancer / benign bile duct stricture, AIDS cholangiopathy, Parasites (Asia) – ascaris /
clonorchis
Intrahepatic Etiologies
 Viral hepatitis, Drugs, Alcoholic hepatitis, ischemic liver injuries, Genetic disorder (Dubin
Johnson, rotor syndrome), TPN, Pregnancy, Organ transplant, Primary biliary cholangitis,
Infiltrative liver disease (TB/fungus/metastasis/lymphoma)
Steps In Jaundice Evaluation
  History  dark urine, yellow skin and sclera, abdominal pain, weight loss, white stool
o White stool suggests cancer blocked the CBD
o Ask about drugs, herbs, dietary supplements, alcohol, previous GB surgeries, HIV,
hepatitis risk factors
 Physical Exam  Hepatomegaly, Scleral Icterus, Spiders, Palpable Gallbladder
 Labs  Total and Direct Bilirubin, GGTP, AST, ALT, CBC, Prothrombin Time
 Radiologic Exam
o Sonogram liver/GB almost always first test (cheap, no radiation) best for stones!!!
o CT Abdomen – shows pancreas well
o Possible MRI/MRCP (magnetic resonance cholangiopancreatography)
o Endoscopic retrograde cholangiopancreatography (ERCP)
 Dangerous but can remove CBD stones
o HIDA scan (non-visualization of gallbladder suggests acute cholecystitis
Gallstones  6% of men, 9% of women, most asymptomatic
Stone Types
 75% Cholesterol (yellow-brown faceted)
 25% are calcium bilirubinate pigmented (black, small, irregular)
 15% radiopaque (2/3 pigmented, 1/3 cholesterol)
 Cholesterol stones 50 – 100% cholesterol
o 1mm – 4 cm
o Women, obese, multiparous, >40, birth control
 Pigmented stones
o Elderly, male = female, increased in Asians
o Increased in cirrhosis, hemolysis, certain parasites
Presentation
 15-25% become symptomatic in 10-15 years
 Biliary colic (intermittent, intense, RUQ or epigastric pain radiating to back or shoulder) is the
most common symptom
o Associated with diaphoresis, nausea, vomiting
o Presence of colic increase risk of complications including CBD stone, acending
cholangitis, and pancreatitis
Diagnosis
 US  echogenic foci that casts an acoustic shadow
 Rarely seen on plain x-ray and frequently missed on CT scan
Treatment
 Asymptomatic
o Prophylactic cholecystectomy (chole) not recommended
o Chole is recommended for patients at risk of GB CA
 Rare, most are found incidentally
 High rates in South America
 Porcelain GB is associated with CA
 GB polyps larger than 5-10 mm
o Primary Sclerosing cholangitis, salmonella
 Symptomatic
o Laparoscopic GB removal is standard of care
o Ursodeoxycholic acid may dissolve small stones but there is a high recurrence rate and
the drug can damage the liver
 Prophylactic Chole
o Sickle cell disease, hereditary spherocytosis because of hemolysis/ pigmented stones
perform gallbladder removal if abdominal surgery for another reason performed
o ? Gastric bypass (30% get stones)
o ? Large >3cm gallstones (higher Gallbladder cancer risk)
Acute Cholecystitis  Associated with cystic duct obstruction and infected bile
Presentation
  Right upper quadrant pain, fever
 Increased white blood cell count, (+) Murphy’s sign, RUQ tenderness
o 90% have gallstones, 10% acalculus cholecystitis (critically ill patients, high mortality)
 Histologic changes range from mild edema, acute inflammation to necrosis and gangrene
 Can have hydrops of Gallbladder (cystic duct stone obstruction leading to gallbladder distention
filled with colorless fluid
Differential
 IBS, Sphincter of Oddi dysfunction, Appendicitis, Hepatitis, Pancreatitis, Peptic ulcer disease,
Bowel perforation, Cardiac ischemia, Pneumonia RLL
Imaging
 Ultrasound  first test, acute cholecystitis suggested by
o Gallbladder wall thickening
o Sonographic Murphy sign (severe pain when patient inhales while u/s probe pressing
over GB – causes patient to immediately stop inhaling
 Cholescintigraphy (HIDA scan) if diagnosis in doubt after sonogram
o Test positive if gallbladder doesn’t fill with technetium labeled iminodiacetic acid
o False positive in severe liver disease, TPN (GB already maximally filled because of
prolonged lack of stimulation due to fasting
o Previous biliary sphincterotomy
Treatment
 NPO
 IVF
 Analgesics
 2nd or 3rd generation cephalosporin + metronidazole
 Surgery within 24 hours of acute cystitis
Complications
 Gangrene, Fistulas, Perforation  peritonitis
Chronic Cholecystitis  Thickening of gallbladder wall associated with stones
o ? Recurrent attacks of acute cholecystitis leading to fibrosis
 HIDA fractional gallbladder excretion – if low <30% suggestive of chronic cholecystitis or small
gallstones not seen on sono
Choledocolithiasis  Stasis of extra hepatic biliary tree (stone, cancer causing obstruction of bile duct)
and Ascending  Infection with E-coli, Klebsiella, Enterobacter, Enterococcus or anaerobes such as Bacteroides or
Cholangitis Clostridia
Symptoms
 Charcots triad: fever, jaundice, and abdominal pain
 Reynolds pentad: Triad + AMS and hypotension
Labs
 Elevated WBC, GGTP, Total bilirubin, ALT, AST
Imaging
 If Charcots or Reynolds is present you may skip to ordering an ERCP
 If Charcots or Reynolds is absent begin with US then MRCP
Treatment
 MRCP then Chole
Pancreas Autoprotection of Pancreas
 Pancreatic proteases in proenzyme form
 Low intracellular calcium in acinar cell promotes destruction of
 Spontaneously activated trypsin
 Acid base balance
 Synthesis of protective protease inhibitors
 Loss of any of these four protective mechanisms can lead to premature enzyme activation and
pancreatitis
Activation of Pancreatic Enzymes
 Initial phase causes acinar cell injury (trypsin most important)
 Second phase is activation, chemoattraction of leukocytes,
  Macrophages in pancreas
 Third phase activated proteolytic enzymes, cytokines damage distant organs
Regulation of Pancreatic Secretion
 Gastric acid stimulates release of secreten from duodenal mucosa (S cells) which causes secretion
of water and electrolytes from pancreatic duct cells
 Long chain fatty acids, essential amino acids and HCl stimulate release of CCK
(Cholecystokinin) from duodenal mucosal ito cells. CCK promotes enzyme secretion from acinar
cells.
 Parasympathetic nervous system via vagas nerve also controls pancreatic secretion
Pancreatic Enzymes
 **Work best in alkaline environment
 Amylase – Hydrolyzes starch to oligosaccharides and maltose
 Lipase, Phospholapse A2 and cholesterol esterase break down fats
 (bile salts activate phospholipase A and cholesterol esterase)
 Endopeptidases include trypsin, chymotrypsin which act on internal peptide bands
 Exopeptidases (Carboxypeptidases, aminopeptidases) act on free carboxyl and amino-terminal
ends.
 Proteolytic enzymes are secreted as inactive zymogen precursor
Acute Pancreatitis Classification
 “Interstitial edematous” defined as inflammation of pancreatic parenchyma and peripancreatic
tissues without necrosis
 “Necrotizing acute pancreatitis” defined as inflammation of parenchyma and surrounding tissues
plus necrosis
Pancreatitis Severity
 Mild – no organ failure or local complications
 Moderately severe – no organ failure in first 48 hours
 Severe persistent organ failure > 48 hours involving one or more organs i.e. renal failure, ARDS,
CHF
 Multiple scoring formulas to assess severity and need for aggressive fluid resuscitation, ICU care
Indication for ICU Monitoring
 Severe acute pancreatitis
 Pulse <40, >150
 Systolic BP <80
 Respiration rate > 35
 Serum Na <110 or >170 Serum potassium < 2.0 or > 7.0
 Ph < 7.1 or > 7.7
 Glucose > 800
 Calcium > 15, ??, coma
Bad Prognostic Sign After Admission
 Apache II score > 8
 Persistent Sirs > 48 hours
 Elevated hematocrit > 44%, BUN > 20 mg/dl or creatinine > 1.8 mg/dl
 Age > 60
Diagnosis
 Amylase and Lipase both useful for making diagnosis but serial measurements not helpful for
prognosis/treatment.
 Levels >3X normal quite suggestive
 Must rule out gut perforation, ischemia and infarction
 No correlation between height of amylase/lipase elevations and severity of pancreatitis
 Patients with acidemia may have spurious amylase elevations (i.e. DKA which usually presents
with abdominal pain)
Other Labs
 Elevated WBC
 Elevated Hematocrit due to hemoconcentration
 Elevated BUN (Loss of plasma to retroperitoneal space)
  Hyperglycemia due to decreased insulin release, increased glucagon release
 Hypocalcemia – multifactorial but may be due to saponification of calcium to areas of fat
necrosis
 Elevated Bilirubin due to swelling of pancreatic head against CBD (common bile duct) of CBD
stone
Management
 Aggressive hydration with normal saline or Ringers solution
3 ml/kg/hr due to 3rd spacing – most aggressive in first 24 hours
 Watch for CHF
 Reassess pulse, urine output, creatinine, pulse OX frequently to assess need for aggressive
hydration
 Low urine output could be due to acute tubular necrosis or dehydration
 Pain control – Opiates
 Nutrition important – small bowel or NG tube for enteral feeding better than TPN
 Antibiotics – not for prophylaxis, only for infection of OTHER organ or infected necrosis
Monitoring
 O2 saturation
 Urine output
 Electrolytes
 Glucose
 Refeed within first 24-48 hours in mild pancreatitis without ileus
 Severe pancreatitis necessitates TPN
Complications
 Get CT abdomen if deterioration in 72 hours to look for necrosis, local complications
 Pseudocyst – walled off fluid collections
o Usually outside pancreas (develop late)
o Most asx and don’t need drainage
o Complications: bleeding, pain, infection
 Necrosis
 Peripancreatic fluid collections
 Infected necrosis
 Splenic vein thrombosis (variceal bleed)
 Pseudoaneurysm (GI bleed)
Management of Inciting Conditions
 ERCP if retained stone in common bile duct
o May need endoscopic sonogram or MRCP to look for common bile duct stone.
o Eventual cholecystectomy
 Treat hyperglycemia
 Treat hypercalcemia
Etiology
 Gallstones (35-40% ) more in middle age to older patients
 Biliary sludge (viscous, ? Microlithiasis)
 Alcohol
 Cigarette smoking!
 Elevated Triglycerides
 Post ERCP
 Medications (i.e. Cannabis, Furosemide, Mesalamine, 6MP, Tetracycline)
 Idiopathic
 Infections (CMV, Varicella Zoster, Coxsackievirus, Ascaris)
 Trauma
 Autoimmune (Elevated IgG4)
Clinical Symptoms
 Epigastric pain radiating to back – SEVERE!
 Relief of pain in fetal position
 Nausea / vomiting
Infected Necrosis Overview
 Seen in 10-14 days – initiate antibiotics if suspect
 Fever/failure to improve in 10-14 days, elevated white blood cells
 Diagnose by CT guided fine need aspiration/culture gram stain
 Immediate or delayed necrosectomy (percutaneous or laparoscopic or open drainage) more easily
done late when walled off
 If sterile – conservative therapy/ stop antibiotics
Sterile Necrosis Complications
 Gastric outlet obstruction
 Abdominal pain / nausea and vomiting
 Spillage of pancreatic enzymes into peritoneum because of transected pancreatic duct

Chronic Pancreatitis  Occurs most often in patients with alcoholism

 Tobacco smoking is a risk factor
Symptoms
 Persistent epigastric and/or RUQ pain
 Anorexia, weight loss, nausea, vomiting, constipation, flatulence, and weight loss
Signs
 Tenderness, guarding, ileus, steatorrhea
Labs
 Amylase, lipase, ALP, bilirubin may all be elevated
Imaging
 X-ray and CT may demonstrate calcifications
 ERCP is most sensitive study
 MRCP and EUS are less invasive alternatives to ERCP
Treatment
 Low fat diet
 No etoh
 Non opioids for pain
 Panc supplements
 Surgery may be needed
Pancreatic Cancer Etiology
 Ductal adenocarcinoma – 85% of cases, poor long-term prognosis, 15% amenable to surgery
(small, no metastasis, no vascular invasion, Whipple procedure if in head of pancreas)
Symptoms
 Weight loss
 Abdominal pain (epigastric to back)
 Jaundice (if in head of pancreas)
 Steatorrhea
Neuroendocrine Tumors
 Also known as islet cell tumors
 Rare, slow growing
 Can secrete peptide hormones including insulin, gastrin (Zollinger Ellison Syndrome) vasoactive
intestinal peptide, glucagon
 CT, MRI, endoscopic ultrasound and localized venous sampling of hormone levels can be helpful
in diagnoses
 Zollinger-Ellison Syndrome – multiple ulcers in duodenum, treated with high dose proton pump
inhibitors
Physical Exam
 Courvoisier’s sign (palpable distended gallbladder due to bile duct blockage
 Hepatomegaly (liver metastasis)
 Epigastric mass
 Ascites
 Scleral Icterus
 Location of mass i.e. body/tail can affect symptoms/physical exam
  Deep venous thrombosis
Labs
 CA19/9 not specific or sensitive
 Elevated liver function tests
 Anemia of chronic disease

Diagnosis
 CT scan
Treatment
 Whipple if localized to head of pancreas
o 5 year survival rate 20-25%
 Neoadjuvant and/or adjuvant chemo/radiation improves survival rate