THE GENERAL DIAGNOSTICS OF THE , AND PANCREATIC DISEASES László Kalabay MD PhD

2018/2019 Academic Year, 2nd Semester 4th Year

SEMMELWEIS UNIVERSITY 3rd Department of Internal http://semmelweis.hu THE GENERAL DIAGNOSTICS OF LIVER DISEASES

SEMMELWEIS UNIVERSITY 3rd Department of http://semmelweis.hu Liver diseases 1

Inherited hyperbilirubinemia Liver involvement in systemic diseases • Gilbert’s syndrome • Sarcoidosis • Crigler-Najjar syndrome I, II • Amyloidosis • Rotor syndrome • Glycogen storage diseases Viral • Celiac disease • A, B, C, D, E, other (EBV, CMV), • Tuberculosis cryptogenic Cholestatic syndromes Immune and autoimmune liver • Benign postoperative diseases • of sepsis • Primary biliary (PBC) • Total parenteral nutrition-induced • (CAH) jaundice • Sclerosing cholangitis (PSC) • Cholestasis of pregnancy • Graft-versus-host disease (GVHD) • and cholangitis • Allograft rejection • Extrahepatic biliary obstruction (stone, stricture, cancer) Source: Harrison's Principles of Internal • Biliary atresia Medicine 19th Ed. McGraw-Hill 2015 • Caroli’s disease • Cryptosporidiosis Liver diseases 2 Genetic liver diseases Drug-induced • α1-antitrypsin deficiency • Hepatocellular (INH, acetaminophen) • Hemochromatosis • Cholestatic (methyltestosterone) • Wilson’s disease • Mixed (sulfonamides, phenytoin) • Benign recurrent intrahepatic • Micro- and macrovesicular steatosis cholestasis (BRIC) (MTX, fialuridine) • Progressive familial intrahepatic Vascular injury cholestasis (PFIC) types I-III • Venoocclusive disease • Others (galactosemia tyrosinemia, • Budd-Chiary syndrome cystic fibrosis, Newman-Pick • Ischemic hepatitis disease, Gaucher’s disease) • Passive congestion Alcoholic liver diseases • Portal vein • Acute fatty liver • Nodular regenerative hyperplasia • Acute Mass lesions • Laënnec’s cirrhosis • Hepatocellular carcinoma (HCC), • Nonalcoholic fatty liver cholangiocarcinoma, adenoma, focal • Steatosis nodular hyperplalsia (FNH), metastatic • Steatohepatitis (NASH) tumors, abscess, cysts, hemangioma Acute fatty liver of pregnancy Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 History and symptoms

Aspecific constitutional More liver-specific • Fatigue • Jaundice • Weakness, malaise • Dark urine, light stools, • Nausea, less commonly Pruritus (in cholestasis) vomiting (vomitus • Fever matutinus, too) • Diminished libido • Poor appetite • Anorexia, weight loss • Abdominal pain, bloating, and discomfort in the RUQ region Bloating • Abdominal swelling (ascites) Source: Harrison's Principles of Internal • Change in sleep pattern and Medicine 19th Ed. McGraw-Hill 2015 behavior Major risk factors for liver disease • Details of alcohol use • (incl. herbal compounds, birth control pills, OTC medications) • Personal habits • Sexual activity • Travel • Exposure to jaundiced or other high-risk persons • IV drug abuse • Recent • Remote or recent transfusion with blood or blood products • Occupation Source: Harrison's • Accidental exposure to blood or needlestick Principles of Internal Medicine 18th Ed. • Familial history of liver disease McGraw-Hill 2012 Physical examination Inspection: icterus (sclera, skin) spider teleangiectasias, palmar erythema, excoriations (pruritus!), xanthomas, xanthelasmas (hypercholesterinemia), changes in hair pattern (female type in males), gynecomastia, soft, small testes, prominence of cutaneous veins, haemorrhoid veins (portosystemic shunts) Palpation: size-form-consistency: smooth, nodular, hard, rockhard, firm-sharp edge, rounded edge, irregular edge, abdominal mass, tenderness ascites (ballottment) • cholecyst: Courvosier’s sign • spleen (splenomegaly in ) Percussion: ascites (as dullness), size and shape of the liver neurologic examination - flapping tremor Constellation of symptoms reported by patients with acute hepatitis B virus (HBV)

Source: Images MD Icterus Spider nevi

Source: slideshare.net Source: Medical-On-Line Alamy Ascites

Source: en.wikipedia.org Source: murrasaca.com Severe protein malnutrition in a patient with end-stage liver disease

Source: Images MD Large esophageal varices

Source: Images MD Pruritus and palmar erythema

Source: imgarcade.com Source: Medical-On-Line Alamy Source: empills.com Metabolism in liver diseases

CARBOHYDRATE METABOLISM: • maintenance of blood glucose level in fasting state is impaired (glycogenolysis, gluconeogenesis) • glucose intolerance (insulin is diverted to peripheral circulation via portosystemic shunts) LIPID METABOLISM: • in cholestasis, se. cholesterin , phospholipids , xanthomas, xanthelasmas AMINO ACID AND PROTEIN METABOLISM: • albumin (hypalbuminaemia, edema, ascites) • clotting factors (prothrombin!) • transferrin • 1-antitrypsin BIOTRANSFORMATION AND DETOXIFICATION: • ammonium  urea (Krebs-Henseleit) = hyperammoniemia Important diagnostic tests in common liver diseases Disease Test Hepatitis A Anti-HAV IgM Source: Harrison's Hepatitis B Principles of Acute HBsAg and anti-HBc IgM Internal Chronic HBsAg and HBeAg and/or HBV DNA Medicine 19th Ed. Hepatitis C Anti-HCV and HCV DNA McGraw-Hill Hepatitis D (delta) HBsAg and anti-HDV 2015 Hepatitis E Anti-HEV Autoimmune hepatitis ANA, SMA, se. IgG↑, compatible histology Primary biliary cirrhosis AMA, se. IgM↑, compatible histology Primary sclerosing cholangitis p-ANCA, cholangiography Drug-induced liver disease History of drug ingestion History and compatible histology Nonalcoholic steatohepatitis USG or CT evidence of fatty liver, compatible histology α1 Antitrypsin disease α1-AT levels↓, phenotypes PiZZ or PiSZ Wilson’s disease Se. ceruloplasmin↓, urinary copper↑, hepatic copper level↑ Hemochromatosis Iron saturation↑, se. ferritin↑, testing for HFE gene mutations Hepatocellular cancer ElevatedAFP > 500; USG or CT image of mass A simplified diagnostic approach in patients presenting with acute hepatitis Serologic tests of patient's serum Diagnostic interpretation HBsAg IgM IgM anti- anti-HAV anti-HBc HCV + - + - Acute hepatitis B + - - - Chronic hepatitis B + + - - Acute hepatitis A superimposed on chronic hepatitis B + + + - Acute hepatitis A and B - + - - Acute hepatitis A - + + - Acute hepatitis A and B (HBsAg below detection threshold) - - + - Acute hepatitis B (HBsAg below detection threshold) - - - + Acute hepatitis C Markers of inflammation in liver disease

• SGOT = serum glutaminic acid-oxalacetic acid transaminase = ASAT = aspartate aminotransferase. Present in mitochondria and cytoplasm. • SGPT = serum glutaminic acid-pyruvic acid transaminase = ALAT = aspartate aminotransferase. Present in cytoplasm. → hepatocyte damage • -glutamyl transpeptidase (GT) Markers of cholestasis

• Alkaline phosphatase (ALP, SAP) • Leucine aminopeptidase (LAP) • 5’-nucleotidase Tests of protein synthetizing capacity of the liver

SERUM ALBUMIN AND GLOBULIN: • albumin decreases (so is colloid osmotic pressure) • globulins increase, A/G ↓ PROTHROMBIN TIME: • vitamin K-dependent clotting factor, produced exclusively by the liver Zone electroph oresis pattern in liver cirrhosis Other serum markers of liver disease

• Liver-specific glycoproteins: α2-macroglobulin • Acute phase reactants: – positive: C-reactive protein, (CRP), α1-acid glycoprotein (orosomucoid), serum amyloid A (SAA) – negative: albumin, transferrin, fetuin-A • Serum lipids and lipoproteins • Elements: iron, copper Evaluation of abnormal liver tests

Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 Evaluation of chronically abnormal liver tests

Source: Harrison's Principles of Internal Medicine 19th Ed. W/U: workup McGraw-Hill 2015 Variant syndromes in autoimmune hepatitis

Source: Images MD Mitochondrial and smooth muscle antibodies Imaging techniques in liver disease

• Ultrasonography • CT • MRI • Angiography • Fibroscan on abdominal USG

Source: Images MD Ultrasound and liver scan: hepatic angioma

Source: Images MD Ultrasound: periportal fibrosis

Source: Images MD CT: small hepatocellular adenoma (upper) and cyst (lower) in the liver

Source: Images MD Multiple liver abscess

Source: Images MD Abscess on liver 99Tc scan

Source: Images MD MRI: Hepatocellular carcinoma

Source: Images MD MRI for hepatic metastases of colon cancer

Source: Images MD Hepatic arteriogram in focal nodular hyperplasia

Source: Images MD Portal venography

Source: Images MD Positron emission tomography for hepatic metastases of colon cancer

Source: Images MD Fibroscan - alternative to liver biopsy?

Source: samitivehospital.com Liver biopsy

A, Prominent portal inflammation and occasional peripheral piecemeal necrosis.

B, Section displaying one of many portal-containing lymphoid aggregates with germinal center formation. Portal lymphoid infiltrates with germinal center formation, although not pathognomonic, occur with relatively increased frequency in chronic hepatitis C.

Source: Images MD Fatty liver (left) and cirrhosis (right)

Source: Images MD Primary biliary cirrhosis

Source: Images MD Genetic testing

• HCV • Hemochromatosis (HFE) • Wilson’s disease (ATP7) PCR

For the determination of viral copy number („viral load”) in hepatitis B and hepatitis C THE GENERAL DIAGNOSTICS OF THE BILIARY TRACT DISEASES

SEMMELWEIS UNIVERSITY 3rd Department of Internal Medicine http://semmelweis.hu Blood (plasma) hemoglobin (70%) other heme Intestinal The entoero- proteins (30%) lumen RES hepatic verdoglobin

biliverdin circulation of

0.5 mg% bilirubin bilirubin bilirubin Biliary tract LIVER mesobilirubin bilirubin-glucuronide urobilinogen stercobilinogen Portal vein

Hemorrhoidal veins

Kidney

Urine urobilinogen Stool stercobilin urobilin urobilin approx. 4 mg/day approx. 200 mg/day The hepatobilary tree

Source: Images MD Characteristics of pain of acute abdomen

Source: Szabó Sz. et al. Családorvosi Fórum 2002/1_2-8. (2002) Symptoms Cholelithiasis • Predisposing factors: 3F: female, fat, forty/fifty • Occur following fatty meal • Typically crampy pain n in the right upper quadrant, radiating to the tip of the scapula Laboratory findings • Signs of inflammation, more expressed when cholecystitis is present. elevated ESR, CRP, leukocytosis with the shift to the left • Signs of obstruction only in choledocholithiasis Treatment • Cholecystectomy (laparoscopic preferred), in case of cholecystitis: (amoxicillin, metronidazole) Complications • Acute and chronic cholecystitis (gallbladder cc!) • Choledocholithiasis, biliary tract obstruction • Hydrops, empyema • Perforation of the cholecyst • Acute cholecystitis

Symptoms • as above + fever, chills Laboratory findings • Elevated ESR, CRP, leukocytosis with the shift to the left Treatment • Cholecystectomy (emergency or elective) • Antibiotics (amoxicillin, metronidazole) Choledocholithiasis

Symptoms • Typical pain + jaundice, dark urine, clay-like stool Laboratory findings • Direct hyperbilirubinemia, elevated serum alkaline phosphatase, (less elevated serum transaminases) • Usually signs of inflammation (ESR, CRP, leukocytosis) Differential diagnosis • Other causes of biliary tract obstruction: cholanciocarcinoma, Vater papilla sclerosis or carcinoma, primary sclerotizing cholangitis • Courvoisier’s sign: jaundice with painless palpable gallbladder • Surgical: choledochotomy, cholecystectomy • ERCP Diagnostic evaluation of the gallbladder 1

Diagnostic advantages Diagnostic limitations Comment Plain abdominal X-ray Low cost Relatively low yield Pathognomic findings: Readily available ?Contraindicated in calcified , pregnancy limey bile, , emphysematous cholecystitis, gallstone ileus Gallbladder ultrasound (USG) Rapid; Accurate Bowel gas, massive Procedure of choice to identification of gallstones obesity, ascites, detect stones (>95%); Simultaneous recent barium study scanning of gallbladder, Not limited by liver, bile ducts, pancreas; jaundice, pregnancy „Real-time” scanning allows assessment of gallbladder volume, contractility; May detect very small stones Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 Diagnosis of stone disease by ultrasound

Source: Images MD Diagnostic evaluation of the gallbladder 2

Diagnostic Diagnostic limitations Comment advantages Radioisotope scans (HIDA, DIDA, etc.) Accurate ?Contraindicated in Indicated for identification of pregnancy confirmation of cystic duct Se Bi >103-205 uM/L suspected acute obstruction Cholecystogram low cholecystitis Simultaneous resolution Less sensitive and less assessment of bile specific in chronic ducts cholecystitis Useful in diagnosis of acalculous cholecystopathy, esp. if given with CCK to assess gallbladder emptying

Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 Healthy subject compared with patient with cholelithiasis

Source: Images MD Diagnostic evaluation of the bile ducts 1

Diagnostic Diagnostic Contra- Compli- Comment advantages limitations indications cations Hepatobiliary ultrasound (USG) Rapid; Bowel gas, None None Initial simultaneous massive procedure of scanning of obesity, choice in gallbladder, ascites, investigating liver, bile barium, portal possible ducts, biliary tract pancreas obstruction obstruction Poor visualization of distal

Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 Ultrasonography of duct stones is not as reliable as of those in the bile duct

Source: Images MD Diagnostic evaluation of the bile ducts 2 Diagnostic Diagnostic Contra- Compli- Comment advantages limitations indications cations Computer tomography (CT) Simultaneous Extreme Pregnancy Reaction to Indicated for scanning of cachexia iodinated evaluation gallbladder, liver, Movement contrast, if of hepatic or bile ducts, artifact used pancreatic pancreas Ileus masses Accurate Partial bile tract Procedure identification of obstruction of choice in dilated bile ducts, investigating masses High cost possible Not limited by May not be biliary jaundice, gas, readily available obstruction obesity, ascites if diagnostic High-resolution limitations image prevent USG Guidance for fine-needle biopsy Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 CT of the biliary tract: choledocholithiasis (left) and gallbladder carcinoma with local invasion and a separate metastasis near a percutaneous transhepatic biliary stent (right)

Source: Images MD Diagnostic evaluation of the bile ducts 3

Diagnostic advantages Diagnostic Contra- Compli- Comment limitations indications cations Magnetic resonance cholagiopancreatography (MR) Useful modality for Cannot Some metal visualizing pancreatic and offer alloy biliary ducts therapeutic implants Can identify pancreatic intervention duct dilatation or stricture, pancreatic duct stenosis, and pancreas divisum Has excellent sensitivity for bile duct dilatation, biliary stricture, and intraductal abnormalities

Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 MR of the biliary tract: choledocholithiasis (left), cholangiocarcinoma surrounding the middle hepatic vein and a second lesion posteriorly and medially near the spine (right)

Source: Images MD Diagnostic evaluation of the bile ducts 4

Diagnostic Diagnostic Contra- Compli- Comment advantages limitations indications cations Endoscopic retrograde cholangiopancreatogram (ERCP) Simultaneous Gastroduodenal Pregnancy Cholangiogram pancreatography obstruction Acute Cholangitis, of choice in: Visualization/biopsy ?Roux en Y pancreatitis sepsis Absence of of ampulla and biliary-enteric ?Severe Infected dilated ducts anastomosis cardiopulmonar pancreatic ?Pancreatic, Best visualization of y disease pseudocyst ampullary or distal biliary tract Perforation gastroduodenal Bile or pancreatic (rare) disease cytology Hypoxemia, Prior biliary Endoscopic aspiration surgery sphincterotomy and PTC stone removal contraindicated Biliary manometry or failed Not limited by Endoscopic ascites, sphincterotomy coagulopathy, a treatment abscess possibility Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 ERCP: choledocholithasis (top left), patent pancreatic and occluded common bile duct (bottom left) and long stricture of the common hepatic duct (bottom right)

Source: Images MD Sphincterotomy and stone extraction of common bile duct stones

Source: Images MD Diagnostic evaluation of the bile ducts 5

Diagnostic Diagnostic Contra- Compli- Comment advantages limitations indications cations Percutaneous transhepatic cholangiogram (PTC) Extremely Nondilated or Pregnancy Bleeding Largely successful when sclerosed Uncorrectable Hemobilia replaced by dilated ducts are ducts coagulopathy Bile CT and dilated MRI Massive Bacteremia, Best visualization ascites sepsis Usually of proximal biliary Hepatic initial tract abscess cholangio- Possible separate gram of visualization of choice obstructed left when bile ductal system ducts are Bile dilated cytology/culture Percutaneous transhepatic drainage Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 Percutaneous transhepatic cholangiography (PTC): extensive perihilar cholangiocarcinoma with extension into secondary intrahepatic branches

Source: Images MD Diagnostic evaluation of the bile ducts 6

Diagnostic Diagnostic Contra- Compli- Comment advantages limitations indications cations Endoscopic Ultrasound (EUS) Most sensitive method to detect ampullary stones

Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015

Periampullary tumor THE GENERAL DIAGNOSTICS OF PANCREATIC DISEASES

SEMMELWEIS UNIVERSITY 3rd Department of Internal Medicine http://semmelweis.hu The diagnosis of pancreatic diseases - general considerations • Relative inaccessibility to direct examination and nonspecific nature of abdominal pain • >90 % of the pancreas must be damaged before maldigestion of fat and protein is manifested. • Pancreatic exocrine function becomes abnormal only when >60% of exocrine function has been lost • : severe, constant epigastric, belt-like pain that radiates through to the back, along with an elevated blood amylase level • : hypertriglyceridemia, vitamin B12 , hypercalcemia, hypocalcemia, hyperglycemia, ascites, pleural effusion, and chronic abdominal pain with normal blood amylase levels. Cullen’s sign in acute panrcreatitis

Source: Images MD Peritoneal aspirates in acute pancreatitis

The color of the peritoneal aspirate of patients with acute pancreatitis can differentiate mild from severe disease. The darker the color (caused by blood, due to hemorrhagic pancreatitis), the greater the severity of the disease is. Source: Images MD Fat necrosis seen at surgery

Acute necrotizing pancreatitis

Source: Images MD Pancreatic enzymes in body fluids 1 (frequently used) Test Principle Comment Serum Pancreatic inflammation Simple; 20-40% false positives amylase leads to increased and negatives; reliable if test enzyme levels results are 3 times the upper limit of normal Urine Renal clearance of Inferquently used amylase amylase is increased in acute pancreatitis Ascitic fluid Disruption of gland or Can help establish diagnosis of amylase main pancreatic duct acute pancreatitis; false positives leads to increased occur with intestinal obstruction amylase concentration and perforated ulcer Pleural fluid Exudative pleural effusion False positives occur with amylase with pancreatitis carcinoma of the lung and esophageal perforation Serum Pancreatic inflammation Positive in 70-85% of cases lipase leads to increased enzyme levels Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 Pancreatic enzymes in body fluids 2 (rarely used)

Test Principle Comment Amylase P isoamylases arise from More sensitive than total amylases isoenzymes the pancreas; S in diagnosis of acute pancreatitis; isoamylases are from useful in identifying nonpancreatic other sources causes of hyperamylasemia Serum Pancreatic inflammation Elevated in acute pancreatitis; trypsinogen leads to increased enzyme decreased in chronic pancreatitis levels with ; normal in chronic pancreatitis without steatorrhea and in steatorrhea with normal pancreatic function Pancreatic PP confined almost totally Basal, meal- and hormone- polypeptide to the pancreas; release stimulated (by secretin or CCK) PP (PP) stimulated by nutrients levels decreased in chronic and hormones; such pancreatitis; a fasting PP level > release correlates with 125 pg/mL argues against chronic pancreatic enzyme pancreatitis and pancreatic cancer secretion

Source: Harrison's Principles of Internal Medicine 18th Ed. McGraw-Hill 2012 Serum trypsin levels in chronic pancreatitis

Source: Images MD Morphological studies of the pancreas 1 Test Principle Comment Abdominal Can be abnormal in Simple; normal in > 50% of plain film acute and chronic cases of both acute and chronic pancreatitis pancreatitis Upper GI X- Now obsolete rays Ultrasono- Can provide information Simple, noninvasive; sequential graphy on edema, inflammation, studies quite feasible; useful in (USG) calcification, diagnosis of pseudocyst limited pseudocysts, and mass by interference with bowel gas lesions CT scan Permits detailed Useful in the diagnosis of visualization of pancreas pancreatic calcification, dilated and surrounding pancreatic ducts, and pancreatic structures, pancreatic tumors; may not be able to fluid collection, distinguish between pseudocyst, degree of inflammatory and neoplastic necrosis mass lesions Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 Pancreatic calcification on plain abdominal radiograph

Source: Images MD Barium studies of the GI tract to evaluate patients with suspected pancreatic cancer

Source: Images MD Pancreatic ultrasonography: calcification and dilated, segmented pancreatic duct (left) and a pseudocyst (right)

Source: Images MD A CT scan of the pancreas indicating gas bubbles within the substance of the pancreas

Source: Images MD CT: diffuse pancreatic calcification (left) and a pseudocyst in the head of the pancreas (right)

Source: Images MD Morphological studies of the pancreas 2

Test Principle Comment Endoscopic Cannulation of pancreatic Provides diagnostic retrograde and common bile duct data in 60-85% of cholangio- permits visualization of cases; differentiation pancreatography pancreatic-biliary ductal of chronic pancreatitis (ERCP) system from pancreatic carcinoma may be difficult; now considered primarily a therapeutic procedure Endoscopic High-frequency transducer Can be used to ultrasonography employed with EUS can assess chronic (EUS) produce very high-resolution pancreatitis and images and depict changes pancreatic carcinoma in the pancreatic duct and parenchyma with great detail Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 Arteriogram: „leaking” contrast material from the splenic artery into large pseudocyst

Source: Images MD ERCP: primary sclerosing cholangitis (left) and tapering of distal common bile duct resulting from pseudocyst or fibrosis in the head of the gland (right)

Source: Images MD ERCP: Minimal dilatation of the pancreatic duct (left) advanced chronic pancreatitis, „chain-of- lakes” (right)

Source: Images MD Endosonographic (EUS) image of the body of the pancreas with a visible pancreatic duct (thin arrow) and calcifications within the gland (thick arrow). The circular target structure in the center is the instrument

Source: Images MD Pseudocyst in the pancreas Morphological studies of the pancreas 3

Test Principle Comment Magnetic 3D rendering has been Has largely replaced resonance used to produce very ERCP as a diagnostic cholecysto- good images of the test pancreatography pancreatic duct by a (MR) noninvasive technique Pancreatic Percutaneous biopsy with High diagnostic yield; biopsy with USG skinny needle and laparotomy avoided; or CT guidance localization of lesion by requires special USG technical skills

Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 MR of the pancreas: duct abnormalities

Source: Images MD Computed tomography can also direct a needle aspiration to obtain a tissue diagnosis from a pancreatic mass

Source: Images MD Tests of exocrine pancreatic function 1

Test Principle Comment Direct stimulation of the pancreas with analysis of duodenal contents 1. Secretin- Secretin leads to Sensitive enough to detect pancreozymin increased output of occult disease; involves (CCK) test pancreatic juice and duodenal intubation and HCO3-; CCK leads to fluoroscopy; poorly defined increased output of normal enzyme response; pancreatic enzymes; overlap in chronic pancreatitis; pancreatic secretory large secretory reserve capacity response is related to of the pancreas, currently done the functional mass of at only few medical centers pancreatic tissue 2. Endoscopic Replaces need for Sensitive enough to detect secretin-CCK tube replacement occult disease; avoids intubation test duodenum and fluoroscopy; requires seadation

Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 Tests of exocrine pancreatic function 2 Test Principle Comment Measurement of intraluminal digestion products 1. Microscopic Lack of proteolytic and Simple, reliable; not examination of lipolytic enzymes causes sensitive enough to detect stool for decreased ingestion of milder causes of undigested meat meat fibers and pancreatic insufficiency fibers and fat triglycerides 2. Quantitative Lack of lipolytic enzymes Reliable, reference stool fat brings about impaired fat standard for defining determination digestion severity of malabsorption; does not distinguish between maldigestion and malabsorption 3. Fecal nitrogen Lack of proteolytic Does not distinguish enzymes leads to between maldigestion and impaired protein digestion; malabsorption; low resulting in an increase in sensitivity stool nitrogen Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015 Steatorrhea and diabetes associated with chronic pancreatitis

Source: Images MD Stimulated pancreatic lipase output and fecal fat excretion and stimulated pancreatic trypsin output and fecal nitrogen excretion

Source: Images MD Tests of exocrine pancreatic function 3

Test Principle Comment Measurement pancreatic enzymes in feces 1. Elastase Pancreatic secretion Good sensitivity if stools of proteolytic enzymes not liquid 2. Chymotrypsin Pancreatic secretion Unable to detect chronic of proteolytic enzymes pancreatitis in the absence of steatorrhea

Source: Harrison's Principles of Internal Medicine 19th Ed. McGraw-Hill 2015