Pathophysiology Chapter 37

CHAPTER 37

ALTERATIONS IN FUNCTION OF THE GALLBLADDER AND

EXOCRINE PANCREAS

STRUCTURE AND FUNCTION OF THE PANCREATICOBILIARY SYSTEMPancreaticobiliary System• Gallbladder and cystic duct

• Forms a controlled system to deliver bile to intestinal tract

• Gallbladder: distensible sack about 30-50 ml capacity

• Cystic duct: connects with hepatic duct to form common bile duct

STRUCTURE AND FUNCTION OF THE PANCREATICOBILIARY SYSTEM

(CONT.)Pancreaticobiliary System • Intrahepatic, hepatic, and common bile

duct• Common bile duct forms major aqueduct for

digestive secretions to enter intestinal tract• Ampulla of Vater

• 3 inches long• Runs along duodenum; terminates at ampulla of

Vater• Forms terminating point of main pancreatic duct


(CONT.)Pancreaticobiliary System • Endocrine and exocrine pancreas

• Pancreatic duct• Runs proximally in pancreas• Branches off dorsally to drain tail of pancreas


(CONT.)

EMBRYOLOGY OF THE PANCREATICOBILIARY SYSTEM

3-4 Weeks’ Gestation• Hepatic diverticulum forms from the

primitive foregut• Composed of specialized progenitor liver cells• Eventually forms entire liver, biliary tree, ventral

pancreas• Dorsal pancreas forms from separate outcropping

of cells lying on the opposite side


(CONT.)5 Weeks’ Gestation• Three buds seen in hepatic diverticulum

• Cranial contains hepatoblasts to form liver• Liver sinusoids develops and feed into developing

bile canaliculi• Caudal bud develops into gallbladder


(CONT.)


(CONT.)Second Trimester• Fetus produces bile: gives coloring to the

fetal meconium• Basal bud transforms into the ventral

pancreas

PHYSIOLOGY AND FUNCTION OF BILE FLOW

• Bile produced by hepatocytes in liver; stored in gallbladder• Primary bile acids: choli, chenodeoxycholic acid• Secondary bile acids: deoxycholic acid,

ursodeoxycholic acid, lithocholic acid• Composed primarily of H2O, electrolytes, organic

solute; low protein content• Additional components include pigment

cholesterol phospholipids

PHYSIOLOGY AND FUNCTION OF BILE FLOW (CONT.)

Bile Composition• Primarily H2O, electrolytes, organic

solute• Low protein content• Additional components: pigment,

cholesterol, phospholipids


Bile Functions• Aids in digestion of lipids• Transports waste products

• Bilirubin• Immunoglobulins (IgA)• Toxins• Cholesterol


Gallbladder• Concentrates and stores bile• Fasting state

• Muscular sphincter at ampulla of Vater is contracted; promotes flow of bile into gallbladder

• Half of bile stored; half flows into duodenum• Absorption: 90% of H2O in bile absorbed from bile

in 4 hours


• Bile flow (in sequence): 1st morning meal• Hormonally and neurally regulated contraction of

gallbladder releases concentrated bile into duodenum

• Bile acids • Eventually absorbed again in terminal ileum

(2-3 times)• Travel by portal circulation to be secreted again into

the bile• Small amount of pool enters colon (5%); undergo

bacterial transformation into secondary bile salts


Bile Salts• Dual properties

• Digestion• Absorption of fats from small bowel

• Molecules aggregate into clusters• Micelles surround lipids and allow them to go into

solution• Hydrophilic/hydrophobic


FUNCTIONAL ANATOMY OF THE PANCREAS (CONT.)

• Endocrine pancreas• Insulin• Glucagon• Somatostatin into blood

• Exocrine pancreas• Secretes >1 L of digestive juice into duodenum

every 24 hr


Pancreas Components• Lobular; composed of two fused organs

• Dorsal• Ventral

• Pancreatic juices• Active digestive enzymes: amylase, lipase• Precursor or proenzymes: trypsinogen• Release stimulated by cholecystokinin and

secretin


DISORDERS OF THE GALLBLADDER

• Cholesterol gallstone formation (cholelithiasis)• Etiology

• 20 million (U.S.)• Incidence

• Native Americans > American Caucasians• Women > men (2:1)

• Risk factors• Age• Sex• Obesity (also rapid weight loss in obese)• Variety of medical factors

DISORDERS OF THE GALLBLADDER (CONT.)

• Cholesterol gallstone formation (cholelithiasis)• Pathophysiology

• Three phases• Supersaturation of bile with cholesterol• Nucleation of crystals• Hypomotility allowing stone growth

• Cholecystitis• Inflammation of the gallbladder wall• Related to continued presence of gallstones


Signs and Symptoms: ChronicCholelithiasis• Biliary colic

• Precipitated by a meal (infrequent schedule)• Persistent epigastric (right upper abdominal pain)• Often radiates to back• Increases steadily for >15 minutes, lasts several

hours, then slowly decreases• Related to intermittent obstruction of cystic duct

• Nausea, vomiting, sweating, flatus


Chronic Cholelithiasis• Diagnosis: ultrasound• Treatment

• Watchful waiting• Patients with significant recurrences of biliary colic

• Cholecystectomy• Chemical dissolution of gallstones• Lithotripsy

Disorders of the Gallbladder Disorders of the Gallbladder (Cont.)(Cont.)


Acute Cholecystitis: Acute Inflammationof the Gallbladder Wall• Etiology

• Cholelithiasis present in 90% of patients• Obstruction of cystic duct present in almost all

patients: related to stasis of bile• Bacterial infection may be present


Acute Cholecystitis • If untreated, escalates; gangrene may occur

• Peritonitis• Septic shock• Localized abscess• Cholecystoenteric fistula (fistula between

gallbladder and GI tract)


Acute Cholecystitis• Signs and symptoms

• Severe right upper abdominal pain: radiates to back

• Abdominal tenderness• Fever


Acute Cholecystitis • Acalculous cholecystitis

• Occurs in patients without preexisting gallstones• Males >50 years• Rapid development of gangrene, perforation,

emphysematous cholecystitis, and empyema develops rapidly


Acute Cholecystitis • Risks

• Major surgery • Critical illness• Trauma• Burn-related injury


Acute Cholecystitis • Diagnosis

• Abdominal ultrasound• Presence of stones• Thickened gallbladder wall

• HIDA scan• CT• MRCA• ERCP


Acute Cholecystitis • Treatment

• Chemodissolution (nonsurgical): use of bile acids/organic solvents to dissolve gallstone

• Lithotripsy (nonsurgical)• Breaking up of gallstones using shockwaves• Stones <2 cm


Acute Cholecystitis • Treatment

• Cholecystectomy: mainstay of therapy• Antibiotics (if bacterial infection)• Advanced acute cholecystitis complicated by

gangrene, empyema, or emphysematous changes is a surgical emergency


Chronic Cholecystitis: ChronicInflammation of Gallbladder Wall • Related to persistent low-grade irritation

from gallstones• Related to recurrent attacks of acute

cholecystitis• Predisposing factors

• Diabetes mellitus• Obesity


Chronic Cholecystitis • Signs and symptoms

• Asymptomatic• Leads to complications

• Biliary sepsis• Scarring (porcelain gallbladder)

DISORDERS OF THE PANCREAS (CONT.)

Acute Pancreatitis• Etiology: 1-5:10,000 in U.S. annually• Predisposing factors• Biliary tract disease

• Hypertriglyceridemia• Ethanol-associated (66%)

• Secretion of protein-rich pancreatic fluid• Deposition of inspissated protein plugs• Obstruction of small pancreatic ducts



Acute Pancreatitis: Signs and Symptoms• Steady, boring pain in epigastrium or LUQ

• Increases in intensity• Severe tenderness on palpation• Radiates or penetrates to back• Accompanied by nausea and vomiting

• Abdominal distention• Hypoactive or absent bowel tones

• Low-grade fever


Acute Pancreatitis: Diagnosis• Laboratory

• Increase in amylase and lipase during first 12 hr• Remain elevated for several days• Lipase preferred test

• Elevated aminotransferases• Elevated alkaline phosphatase and

bilirubin• Leukocytosis• Hyperlipidemia• Hypocalcemia


Acute Pancreatitis: Diagnosis • Abdominal x-ray

• Ileus pattern• “Sentinel loop”: distended loop of small bowel in

area of pancreas• Abdominal ultrasound


Acute Pancreatitis: Diagnosis • CT of abdomen

• Gold standard and allows remarkable detail: edema, abscess, cyst formation

• Prognostic assessment: Ranson’s criteria


Acute Pancreatitis: Differential Diagnosis

• Perforated peptic ulcer• Acute cholecystitis• Mesenteric vascular disease



Acute Pancreatitis: Treatment• Mild to moderate

• Conservative management• Withhold oral feedings• Nasogastric suction for adynamic ileus• IV fluid replacement• Analgesics


Acute Pancreatitis: Treatment • Severe

• Nutritional replacement: prevents tissue breakdown

• Calcium and magnesium administration• Control of hyperglycemia• Prevent respiratory, ARF, intraabdominal sepsis• Bacterial infection


Acute Pancreatitis: Treatment • Surgical intervention (abscess or

hemorrhage)• Necrosectomy: debridement of devitalized tissue• Pancreatectomy: major pancreatic resection


Acute Pancreatitis: Complications• Pseudocyst: collection of fluid within or

adjacent to pancreas• Signs and symptoms

• Fever• Tachycardia• Abdominal mass and tenderness

• Management: endoscopic or surgical drainage


Acute Pancreatitis: Complications • Pancreatic ascites: persistent leak in

pancreatic duct into pleural space and mediastinum• Signs and symptoms: painless and massive• Treatment

• Ultrasound• CT• Fluid analysis obtained by aspiration


Acute Pancreatitis: Complications • Pancreatic ascites: management

• Prolonged parenteral nutrition• Endoscopic placement of a stent into main pancreatic

duct• Common bile duct obstruction• Portal or splenic vein thrombosis• Peptic ulcer disease• Chronic fistula formation


Chronic Pancreatitis: Etiology• Mortality (3%-4% yearly)• Predisposing factors

• ETOH consumption• Idiopathic• Hereditary• Hyperparathyroidism (hypercalcemia)• Trauma


Chronic Pancreatitis: Pathophysiology • Presence of chronic inflammatory lesions in

pancreas• Key element: necrosis followed by fibrosis• Persistence of symptoms secondary to

pancreatic dysfunction over weeks and months


• Destruction of exocrine parenchyma and fibrosis• Precedes destruction of endocrine parenchyma• Leads to calcification


Chronic Pancreatitis: Pathophysiology • Increase in protein concentration in

pancreatic juice with reduction in “pancreatic stone protein” (inhibits formation of pancreatic protein plugs)• Leads to calcification—obstruction in flow of

pancreatic juice


Chronic Pancreatitis: Signs andSymptoms• Bouts of acute pancreatitis with progressive

signs of persistent pancreatic dysfunction• Insidious onset of epigastric pain radiating

to back (first symptom)• No pain but sequelae of chronic

pancreatitis(10%-15%)


Chronic Pancreatitis: Signs andSymptoms • Endocrine and exocrine pancreatic

insufficiency• Diabetes: progressive loss of endocrine cells in

pancreatic islets• Malabsorption

• Pancreatic enzyme output <10% of normal• Impairment of vitamins A, D, E, and K

• Weight loss: poor intake related to pain


Chronic Pancreatitis: Complications• Pseudocyst• Pancreatic ascites• Obstruction of common bile duct: surgical

or endoscopic intervention• Thrombosis of portal and splenic veins may

lead to GI hemorrhage related to gastric varices

• Peptic ulcer disease


Chronic Pancreatitis: Diagnosis• History• Physical examination• Laboratory: elevated LFTs, alkaline

phosphatase, and bilirubin levels• Abdominal x-ray• CT• ERCP: suspicious cases unconfirmed with

other tests



Chronic Pancreatitis: Treatment• Pain control

• Absolute abstention from alcohol• Analgesics• Surgical intervention• Celiac plexus block

• Pancreatic sphincterotomy: management of single or multiple stones


Chronic Pancreatitis: Treatment • Pseudocysts (adjacent to stomach or

duodenum): endoscopic drains• Obstruction of bile duct or main pancreatic

duct: biliary/pancreatic stents• Whipple procedure

(pancreaticoduodenectomy)


Chronic Pancreatitis: Treatment• Management of endocrine/exocrine

insufficiency• Low-fat diet• Pancreatic enzyme supplementation• Oral hypoglycemic agents/insulin

Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.


Chronic Pancreatitis: Treatment• Pancreatic enzyme replacement

• Steatorrhea control• Chronic pain management• 20%-30% ETOH-induced disease respond to therapy• Medications

• H2 blocker• Proton pump inhibitor

Education

Pathophysiology Chapter 37