Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

6. HDS GI Repro > Pancreatic and Gallbladder Disorders > Flashcards

Pancreatic and Gallbladder Disorders Flashcards

1
Q

Bile

A
  • Isosmotic w/ plasma
  • Composition:
    • Water (82%)
    • Bile acids (12%)
    • Phospholipids (4%)
    • Cholesterol (0.7%)
    • Bilirubin (0.3%)
  • Bile acids formation
    • Primary bile acids: synthesized in the liver from cholesterol
    • Secondary bile acids: formed from bacterial action in the colon
    • Bile salts are absorbed in the ileum and majority go back to the liver
  • Bile pool = 2-4 grams
    • 500-600 ml of hepatic bile secreted/day
    • Bile circulates 2-3x per meal
    • 90-95% of bile enters the enterohepatic circulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Gallbladder

Histology

A
  • Mucosa is columnar and thrown into folds
  • Rokitansky-Aschoff sinuses: outpouchings of gallbladder mucosa that penetrate into muscle wall
    • May represent acquired herniations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Gallbladder

Motility

A
  • Neural control by parasympathics
  • Most potent physiologic stimulator is cholecystokinin (CCK)
    • Stimulated by long-chain fatty acids, amino acids and carbs
    • Causes gallbladder contraction, relaxation of the Sphincter of Oddi
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Gallbladder

Diseases

A
  • Cholelithiasis (gallstones)
  • Cholecystitis (inflammation)
  • Cholesterolosis (cholesterol deposits)
  • Cancer (gallbladder adenocarcinoma)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Cholelithiasis

Overview

A

“Gallstones”

  • 10-20% of adults in U.S. and western Europe
  • Most are clinically silent (> 80%)
  • Most stones in the U.S (90%) are cholesterol stones
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Cholelithiasis

Epidemiology

A
  • 20 million per year in U.S.
  • 98-99% asymptomatic
  • 1-2% develop sx (biliary colic) per year
    • 50% of those will be asymptomatic in the next year
    • 50% will have another episode within 1 year
    • 1-2% of those will develop complications per year
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Types of Gallstones

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Cholesterol Gallstones

Characteristics

A
  • 75% of gallstones
  • Composition:
    • Pure cholesterol stones ⇒ large and white
    • Mixed cholesterol stones (> 50% cholesterol) ⇒ small and multiple
    • Other components are calcium carbonate, calcium phosphate and calcium bilirubinate
  • Most stones are: radiolucent, 1-3 cm, yellow and multifaceted
  • Formation:
    • Bile supersaturated w/ cholesterol
    • Concentration exceeds capacity of bile salts and lecithin’s to disperse it
    • Cholesterol nucleates into solid crystals
    • Delayed emptying favors further precipitation of crystals around nidus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Cholesterol Gallstones

Risk Factors

A
  • Age: most common in the later part of life
  • Female sex: estrogenic factors predispose
    • ↑ Risk w/ OCPs and pregnancy
  • Obesity
  • Genetics
    • Pima Indians, Scandinavians, those w/ 1st degree relatives affected
    • Genes encoding hepatocyte proteins that transport biliary lipids have association w/ gallstone formation
  • Underlying conditions
    • Crohn’s disease, DM, hypertriglyceridemia
  • Changes in biliary excretion of cholesterol
  • Clofibrate: drug used to lower cholesterol
    • ↓ Cholesterol → bile acids ⇒ ↑ biliary secretion of cholesterol ⇒ ↑ stone risk
  • Rapid weight change: ass. w/ ∆ biliary excretion of bile
  • Conditions of stasis: autonomic neuropathy (DM)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Pigment Gallstones

Overview

A
  • Predominant gallstone worldwide
  • 10-25% of gallstones in the US but higher % in Asians
  • Usually < 1cm, many may be present
  • Seen in conditions w/ ↑ concentration of unconjugated bilirubin in bile
    • Chronic hemolytic anemias (overwhelm deconjugation in biliary tree)
    • Severe ileal dysfunction or bypass
    • Bacterial/parasitic contamination of the biliary tree
    • Infection ⇒ release of microbial Beta-glucuronidases ⇒ hydrolysis of bilirubin glucuronides ⇒ ↓ conjugation in the biliary tree
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Black Pigment Stones

A
  • Increased production of unconjugated bilirubin which complexes w/ calcium
  • Content:
    • Pure calcium bilirubinate or complexes w/ calcium, mucin, glycoproteins, and copper
  • Association:
    • Chronic hemolytic conditions
    • Cirrhosis
    • Sclerosing Cholangitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Brown Pigment Stones

A
  • Colonization of bile by enteric organisms
  • Soft and Flaky
  • Common in Asia
  • Association:
    • Biliary Stasis
    • Infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Cholelithiasis

Clinical Manifestations

A
  • 70-80% asymptomatic
  • Symptomatic stones complications:
    • Biliary colic
    • Cholecystitis
    • Empyema, perforation, fistulas
    • Pancreatitis
    • Ascending cholangitis
    • Gallstone ileus: erosion of stone through GB wall and into ileum w/ subsequent intestinal obstruction
    • Gallbladder carcinoma (association, not necessarily causal)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Biliary Colic

A
  • Can follow a fatty meal
  • Intermittent obstruction of cystic duct by stones
    • ↑ Pressure in gallbladder
    • No inflammation of gallbladder mucosa
  • Symptoms:
    • Severe, epigastric or RUQ pain increasing over 30 mins and constant for 1-5 hrs
    • ± Radiation to right shoulder/scapula
    • Normal labs if uncomplicated
  • Up to 50%/yr will have another episode
  • 1-2%/yr will have a complication
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Cholecystitis

Overview

A
  • Inflammation of the gallbladder
    • Acute
    • Chronic
    • Acute superimposed on chronic
  • Common indication for abd surgery in the US
  • Usually associated w/ gallstones
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Cholecystitis

Pathogenesis

A
  • Chemical injury:
    • Obstruction ⇒ ↑ level of bile salt or acids ⇒ hydrolyzed to lecithin and lysolecithin ⇒ ↑ inflammation
  • Microbials:
    • Bacteria (usu. E. coli or Enterococcus) are present in 80% of acute and 30% of chronic cholecystitis
      • Usually secondary rather than precipitating colonization
    • Protozoa (e.g. cryptosporidium) may be causal in cases of acalculous cholecystitis, particularly in the immunosuppressed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Acute Calculous Cholecystitis

A

90% of acute cholecystitis

  • Impacted stone in cystic duct or GB neck
    • GB chemical irritation
      • Disrupt protective glycoprotein mucus,
      • Exposes epithelium to detergent action of bile salts
    • Acute inflammation of gallbladder mucosa:
      • Prostaglandins released
      • ↑ inflammation of wall w/ edema
      • ↑ intraluminal pressure w/ compromised blood flow
    • Eventually, may develop bacterial contamination
  • 75% preceded by biliary colic
  • Symptoms:
    • Progressive RUQ or epigastric pain, > 6 hrs
    • Murphy’s sign (bedside or sonographic)
    • Fever, anorexia, N/V
    • Leukocytosis, ± mild ↑ LFTs
    • Thick gallbladder wall > 3 mm
  • Can require surgery, have spontaneous resolution, or become chronic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Acute Cholecystitis

Morphology

A
  • Gross:
    • Enlarged, tense, blotchy
    • Covered w/ fibrinous/fibrinopurulent exudate
    • Often identify obstructing stone in GB neck or cystic duct
    • Bile may contain pus (empyema)
  • Micro:
    • Neutrophilic infiltrate
    • Vascular congestion / edema
    • Hemorrhage / ulceration
    • Fibrin
    • Mucosal/mural necrosis
      • Day 3-5
    • Myofibroblastic proliferation
      • Day 5-10
  • If very severe:
    • ± Necrosis (gangrenous cholecystitis)
    • ± Perforation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Acute Acalculous Cholecystitis

A

5-10% of acute cholecystitis w/o obstruction from a stone

  • Pathogenesis involves ischemia
    • See inflammation and edema of wall
    • Further compromises blood flow
    • Bile, mucus and ‘sludge’ may accumulate and block cystic duct
  • Often is insidious
    • Need a high index of suspicion in these pts
  • Males > females (slight effect)
  • Precipitating factors include:
    • Burns
    • Trauma
    • Shock, vasculitis/ischemia
    • Critical/chronic illness (ICU pt)
    • Diabetes, long term TPN
    • Immunosuppression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Gangrenous Cholecystitis

A
  • Gallbladder so inflamed that tissue ischemia results
  • Gas forming organisms
  • Can lead to gallbladder perforation
  • 30% mortality
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Empyema of the Gallbladder

A

Pus around the gallbladder

More severe than traditional cholecystitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Choledocholithiasis

A
  • Obstruction of CBD which obstructs bile flow out of liver and gallbladder
  • Different from cholecystitis in that bilirubin and liver enzymes will be significantly elevated
    • AST/ALT usually < 1,000
  • Bilirubin spills into urine
  • ± Pruritus and acholic stools
  • No urobilinogen (usually malignancy only)
  • Stone removal is key before cholangitis occurs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Cholangitis

A

Impacted stone in CBD causing bile stasis and bacterial superinfection

  • Charcot’s triad: pain, jaundice and fever
  • May become septic
    • Fever, hypotension, higher mortality
  • Reynolds’ Pentad: Charcot’s triad plus hypotension and AMS
  • Need urgent decompression of bile duct
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Porcelain Gallbladder

A
  • Intramural calcification of the gallbladder
  • Risk factor for carcinoma of the gallbladder
  • Plain abdominal film can detect
  • Treatment is prophylactic cholecystectomy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Gallstone Ileus

A
  • Inflammation from cholecystitis causes a fistula from gallbladder directly to small intestine
  • Stone travels through fistula
  • Causes small bowel obstruction at ileocecal valve
  • Plain x-ray shows air in biliary tree and SBO
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Mirizzi’s Syndrome

A

Stone impacted in cystic duct mimics choledocholithiasis in presentation and labs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Chronic Cholecystitis

A
  • Multiple attacks of acute cholecystitis
    • May appear as if it is an acute attack
    • ± Prior dx/sx of acute cholecystitis
  • 90% of pts have stones
  • Morphology:
    • Fibrosis w/ ↑ wall thickness, mucosa usually preserved
    • Mononuclear cells: lymphocytes, plasma cells and MΦ
    • ± Dystrophic calcification in GB wall ⇒ ‘porcelain gallbladder’
    • ↑ Incidence of GB cancer
    • Hydrops: resorption of bile solids and mucin secretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Biliary Tract Disorders

Diagnostic Tests

A
  • Labs
  • Ultrasound
  • CT scan
  • HIDA (hepatobiliary scintigraphy)
  • MRI/MRCP
  • EUS (endoscopic ultrasound)
  • ERCP (endoscopic retrograde cholangiopancreatography)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Liver Labs

A
  • Liver Associated Enzymes (LAE’s) ⇒ Alk phos, GGT, ALT, AST
  • Liver function tests ⇒ Bilirubin, INR, albumin
  • Stages of biliary obstruction:
    • ALT elevation ⇒ within hrs
    • Bilirubin elevation ⇒ within one to several days (CA 19-9)
    • Duct dilation ⇒ within several days
    • Liver labs (LAE and bilirubin) often lag behind
      • Reflect clinical status of pt 6-24 hours before drawn
      • ALT and LAE first to improve, then bili then duct dil, then CA 19-9
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Biliary Tract Disorders

Ultrasound

A
  • Stones appear as mobile, dependent echogenic foci in gallbladder lumen w/ shadowing
  • Sludge appears as layering echogenic material w/o shadows
  • Sensitivity > 95% for stones > 2 mm
  • Stones seen in CBD in 50%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Biliary Tract Disorders

CT scan

A

Not great for detecting uncomplicated stones

Excellent test for detecting complications such as:

Abscess, gallbladder perforation, CBD stone, and pancreatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Biliary Tract Disorders

Hepatobiliary Scintigraphy (HIDA)

A
  • Assessment of cystic duct patency
  • Normal scan: radioactivity in gallbladder, CBD, and small bowel in 30–60 min
  • Positive scan (abnormal): non-visualization of gallbladder w/ preserved excretion into CBD or small bowel
  • Sensitivity 95%, specificity 90% for acute cholecystitis
  • Do not use if bilirubin very high
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Biliary Tract Disorders

MRI/MRCP

A
  • Does not require contrast for stones but does for masses
    • Can’t give contrast w/ GFR < 30 due to Derm condition
  • Best at high stones/common hepatic duct
    • Very sensitive and specific but institution dependent
  • Still lots of false pos and neg’s ⇒ only use if changes management
  • Takes time (1-1.5hr)
  • Does not see stents, calcifications well
  • Can be hard to get/read at night and on weekends
  • Pt cooperation a problem
    • Movement obscures
    • Claustrophobia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Biliary Tract Disorders

EUS (Endoscopic Ultrasound)

A
  • Sometimes used pre-ERCP
  • Not available at all centers
  • Invasive (sedation) but low risk, much lower than ERCP
  • May be better than MRCP at distal stones
  • Allows for fine needle aspiration if tumor suspected
  • Much better at ampullary visualization than MRCP
  • Can rule out ampullary tumors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Biliary Tract Disorders

Endoscopic Retrograde Cholangiopancreatography (ERCP)

A
  • Gold standard test for choledocholithiasis
  • Sensitivity and specificity rates 95%
  • Ability to extract stones (or drain infected bile)
    • Lifesaving in severe cholangitis
  • Complication rate as high or higher than cholecystectomy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Cholesterolosis of Gallbladder

A
  • Accumulation of cholesterol esters and TAGs in MΦ within lamina propria
  • Common, and usually asymptomatic
  • Pathogenesis theories:
    • Supersaturation of bile w/ cholesterol
    • Abnormal lipid transport
    • No association w/ elevated blood cholesterol
  • Gross appearance:
    • Strawberry Gallbladder
      • Yellow color on mucosa
  • Microscopic:
    • Cholesterol esters and triglycerides accumulate in subepithelial “foamy MΦ” and gallbladder epithelium
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Gallbladder Carcinoma

Epidemiology and Associations

A
  • Demographics:
    • F:M ratio is 2:1
    • Affects older population
    • ↑ incidence in Southwest US
  • Associations:
    • Gallstones: present in 95% of cases, BUT only 1-2% of pts w/ gallstones develop GB cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Gallbladder Carcinoma

Characteristics

A
  • Clinical:
    • Sx similar to cholelithiasis
  • Pathogenic factors:
    • Chronic inflammation
      • Stones and infections
  • Growth patterns:
    • Infiltrating
      • More common
      • Poorly defined area of diffuse wall thickening and firmness
      • Deep ulcers can result in penetration through wall to liver or loops of bowel
    • Exophytic (Fungating)
      • Grows into lumen as a cauliflower-like mass
  • Outcome: Dismal
    • Usually unresectable at dx
    • 5 yr survival rate is less than 10%
39
Q

Gallbladder Carcinoma

Subtypes

A
  • Adenocarcinoma (95%)
    • Microscopically Indistinguishable from adenocarcinoma of the bile ducts (cholangiocarcinoma) or pancreatic duct
  • Adenosquamous/squamous (5%)
    • Can see areas of dysplasia in epithelium adjacent to invasive cancer
40
Q

Pancreas
Anatomy

A
41
Q

Pancreas
Embryology

A
  • Arises from fusion of dorsal and ventral buds of the developing duodenum
  • Pancreatic duct = fusion of ventral duct w/ distal portal of dorsal duct
  • Accessory duct of Santorini = persistence of proximal portion of dorsal duct
  • PD forms confluence w/ CBD and empties via Ampulla of Vater into duodenum in ⅔ of people
  • Empties via separate orifice into duodenum in remainder
42
Q

Exocrine Pancreas

A
  • 80-85% of organ
  • Acini: small glandular units
  • Ducts: drainage system
  • Exocrine cells are filled w/ enzymes
  • Pancreatic injury ⇒ failure of protective mechanisms ⇒ autodigestion of pancreatic tissue
  • Protective Mechanisms:
    • Digestive enzymes packaged in secretory granules as inactive proenzymes (zymogens)
      • Proenzymes activated by trypsin
        • Activated in the duodenum
    • Acinar and ductal cells secrete trypsin inhibitors
43
Q

Endocrine Pancreas

A

Islets of Langerhans

Represents only 1-2% of organ

  • Beta cells ⇒ insulin
  • Alpha cells ⇒ glucagon
  • D cells ⇒ somatostatin
  • D1 ⇒ vasoactive polypeptide
  • PP ⇒ pancreatic polypeptide
  • EC ⇒ serotonin and motilin
44
Q

Pancreas

Role in Normal Digestion

A
  • Responsible for the vast majority of chemical digestion in the body
  • Pancreas produces Zymogens (precursors to enzymes)
  • Zymogens become activated to trypsin by enterokinase or trypsin itself
  • Creates a feedback loop and more and more trypsin become activated
45
Q

Pancreas

Congenital Anomalies

A
  • Pancreas divisum
    • Most common (3-10%)
    • Failure of fusion of dorsal and ventral pancreatic primordia in the fetus
    • Most pancreatic tissue drains into duodenum through small-caliber minor papilla
      • ? inadequate drainage ⇒ ↑ susceptibility to pancreatitis
  • Annular pancreas
    • Encircles duodenum
    • Can cause obstruction
  • Ectopic pancreas
    • Stomach, duodenum, other sites
    • Can cause inflammation or bleeding
  • Agenesis
    • Unusual
46
Q

Acute Pancreatitis

Definition

A

Acute Inflammation of the pancreas and associated adjacent organs w/o evidence of chronic pancreatitis

“Intraabdominal burn”

  • Defined clinically as 2 of 3 of the following:
    • Typical pancreatic type pain
    • Radiographic findings of acute pancreatitis
    • Elevations in blood chemistries
      • Typically amylase and/or lipase > 3x ULN
  • Amylase and lipase can be elevated due to other reasons in addition to pancreatitis
    • Amylase alone: paroditis; tumors; ectopic pregnancy; macroamylasemia
    • Amylase and lipase: biliary disease; renal failure; intestinal obstruction, ulceration, or ischemia; and perforated viscus
47
Q

Acute Pancreatitis

Epidemiology

A
  • 5-35/100k
  • ↑ incidence (detection? meds? iatrogenic?)
  • ↑ with ↑ age
    • Onset before 14-15 yrs unusual
      • Unless hereditary, traumatic, anatomic anomaly
  • 250k admissions per year in US (2nd GI)
  • $2 billion in direct costs per year
  • 6th costliest GI disease behind ESLD, cancers, IBD
48
Q

Acute Pancreatitis
Pathogenesis

A
  • Reversible pancreatic parenchymal injury due to inappropriate release and activation of pancreatic enzymes (including trypsin)
    • Tissue destruction (pancreatic parenchyma, fat and blood vessels)
    • Acute inflammatory reaction
  • Duct obstruction ⇒ acinar cell injury
  • Causes deranged intra-cellular transport and the release of activated enzymes
    • Premature/intracellular activation of trypsin
      • Trypsin is the major catalyst for pancreatitis
      • Not amylase or lipase (but later lipase gets to abd fat)
    • Leads to activation of chymotrypsinogen, more trypsinogen, elastase, phospholipase A2, complement ⇒ autodigestion
    • Activates prekallikrein and sets off kinin system
    • Activates coagulation factor XII ⇒ inflammation and small vessel thromboses
  • Enzyme release causes:
    • Proteolysis
    • Lipolysis
    • Hemorrhage
49
Q

Acute Pancreatitis

Etiologies

A
  • Alcohol
    • Excess alcohol intake causes 65% of US pancreatitis
    • Biliary disease + Alcoholism = 80% of acute pancreatitis
    • M:F 6:1 for alcoholism
  • Biliary
    • Gallstones: present in 35-50% of cases
    • M:F 1:3 for biliary tract disease
  • Circulatory issues: shock, vascular thrombosis/embolus, vasculitis
    • Infection: e.g. mumps
    • Can directly injury acinar cells
  • Mechanical trauma
    • Blunt trauma, surgery, ERCP
  • Drugs
  • Metabolic
    • Hypertriglyceridemia, hypercalcemia
  • Idiopathic
  • Other includes: neoplastic; structural; inherited; autoimmune; scorpion bites
50
Q

Acute Pancreatitis

Biliary Causes

A

Gallstones or sludge

  • Most common etiology in world
  • Still 35% in US
  • More in women
  • Usually small ones that don’t obstruct cystic duct or most of CBD (common bile duct) until at major papilla
  • ALT > 150: 50% sensitivity and 90% specificity
  • Treatment:
    • Usually pass on it’s own, but don’t be complacent!
    • If Cholangitis: call GI for ERCP; remove gallbladder
    • If not cholangitis: call surgery just remove gallbladder
51
Q

Acute Alcoholic Pancreatitis

A
  • Alcohol has been shown to cause:
    • Transient ↑ contraction of Sphincter of Oddi
    • Secretion of protein-rich pancreatic fluid
    • Deposit inspissated protein plugs that obstruct small pancreatic ducts
    • Direct toxic effects on acinar cells
  • Take a careful history
  • More in men
  • Lipase 2x amylase?
  • 1st or 2nd most common in US (31-40%)
  • Usually fairly high doses for at least few years
    • Any dose, though, can cause AP
    • Often after cessation (24 hrs after a binge, etc)
  • Why only 10% of alcoholics get pancreatitis?
    • Often have chronic pancreatitis
52
Q

Acute Pancreatitis

Triglycerides Related

A
  • Usually > 1,000: an endocrine emergency!
  • Alcohol raises TAG usually to 400-500 range, can be higher
  • Can have normal amylase and lipase
  • Uncontrolled hyperglycemia can lead to high trigs
  • Often have chronic pancreatitis
53
Q

Acute Pancreatitis

Obstructive/Tumor Related

A
  • Adenocarcinoma
  • Ampullary tumors and intraductal papillary mucinous neoplasm (IPMN)
  • Post-acute pancreatitis with pancreatic duct stricture
  • Pancreas divisum? Controversial
  • Annular pancreas

All unexplained pancreatitis pts > 50 y/o should have a CT 6 wks after episode

54
Q

Acute Pancreatitis

Drug Related

A
  • HIV: didanosine, pentamidine
  • Diuretics: thiazides (sulfa?), ACE Inhibitor
  • Immunosuppressive/antimetabolite: L-asparaginase, azathioprine/6-Mercaptopurine
  • Neuropsychiatric: valproic acid
  • Others: estrogen, Byetta (Exanetide), vitamin A (Accutane), etc.
55
Q

Acute Pancreatitis

Clinical Features and Prognosis

A
  • Severe, steady band like upper abdominal pain
    • Radiate/bore to back in 50%
    • Starts over 10-20 min, not as fast as a perforation
    • Lasts days (longer than biliary colic)
  • 90% vomit
  • Fever
  • Can recur
  • Painless in 5-10%
    • Sometimes dx at autopsy
  • Typically causes ER visit and an admission
    • Unless recurrent/chronic
    • Wide spectrum of severity
  • 30% of choledocholithiasis pts
  • Treat by withholding oral intake, hydration, pain meds
56
Q

Acute Pancreatitis

Early Complications

A

Early (48-72hrs)

  • SIRS / Hypotension
  • Ileus
  • Renal failure
  • Third spacing/ascites
  • Hypoxia
  • Acidosis
  • Cholangitis
  • Hypocalcemia/electrolytes abnormalities
  • Multisystem organ failure
  • Intraabdominal hemorrhage
  • Death
57
Q

Acute Pancreatitis

Late Complications

A
  • Gut failure /malnutrition
  • Hypoalbuminemia
  • Infected necrosis/abscess
  • Biliary obstruction
  • Hospital acquired infections
  • Chronic ventilator dependence
  • Pseudocysts/walled off necrosis
  • Splenic vein thrombosis
  • Death
58
Q

Acute Pancreatitis

Mortality

A

Overall 2-5% and ↓ slightly

  • Interstitial/mild pancreatitis (80% of all cases)
    • ≤ 1% mortality
  • Necrotizing/severe pancreatitis (20% of all cases)
    • 20% mortality, long ICU stays (1-3 months)
  • Infected necrotizing pancreatitis (occurs late)
    • 50% mortality
59
Q

Acute Pancreatitis

Morphology

A
  • Gross:
    • Edematous
    • Firm
    • Yellow and white
    • Red/black clot
  • Microscopic:
    • Parenchymal destruction
    • Acute Inflammation
    • Fat necrosis
    • Destruction of vessels w/ interstitial hemorrhage
60
Q

Acute Pancreatitis

Clinical Evaluation

A
  • Serum markers:
    • Serum Amylase
      • Marked elevation in first 24 hours
    • Serum Lipase
      • Rises 72-96 hours after attack begins
    • May also see glycosuria, hypocalcemia
    • LDH
  • Imaging by CT is useful
  • Can be very serious
    • Necrotizing pancreatitis w/ sequelae including pancreatic abscess and/or pseudocyst
61
Q

Acute Pancreatitis

Specific Exam Findings

A
  • Cullen’s sign
    • Superficial edema and bruising in the subcutaneous fat around the umbilicus
  • Grey Turner’s sign
    • Bruising of the flanks due to retroperitoneal hemorrhage

Note: Neither of these are very common in pancreatitis (less than 3% of cases)

62
Q

Pancreatitis Imaging

A
  • Interstitial pancreatitis
    • Inflamed fat or fluid around the pancreas
    • Swollen, enlarged pancreas
  • Necrotizing pancreatitis
    • Takes a couple of days to develop on imaging
    • Abdomen is distended
    • Pancreas and peri-pancreatic fat dies
    • Weeks later pancreas is replaced by a cystic, necrotic cavity
63
Q

Acute Pancreatitis

Management

A
  • NPO (bowel rest)/ Lots of IV Fluids (lactate ringers)/ Pain control
  • Close clinical monitoring
  • Triage to floor or ICU (intensive care)
  • Imaging:
    • US if gallbladder in situ
    • Wait on CT for a few days unless diagnosis not clear or pt very ill
  • GI consult for cholangitis/biliary obstruction
  • Surgery consult for gallstone/severe/infected necrosis
  • Abx for cholangitis/infected necrosis
  • Enteral feeding beyond lig of Treitz if severe ill (within 48 hrs)
  • Prediction of mortality/danger:
    • Scientific studies (APACHE-O APACHE 2, APACHE 3, Ranson, BISAP, Glasgow, Balthazaar)
    • Prediction of mortality/danger - bedside
      • Repeat labs 6 hrs after presentation, BID labs, esp. electrolytes, Mg2+, Ca2+
      • Have intern look at urine output, abdominal exam, vitals, orthostatics at night
      • EKG, CXR, serial glucoses even non-diabetics
64
Q

Chronic Pancreatitis

Overview

A
  • Permanent damage to the pancreas
  • Prolonged inflammation → irreversible destruction of exocrine parenchyma → fibrosis → destruction of the endocrine pancreas
  • Most common cause is long-term alcohol abuse
  • Most pts are adult males
  • Exocrine/endocrine dysfunction or destruction of such tissue on biopsy
  • Fibrosis seen on biopsy/Endoscopic US
  • Practical: calcifications, pancreatic duct stones, dilated irregular pancreatic duct without mass, “beads on a string”, “chain of lakes” dilated side branches, atrophy without mass
  • What is dilated? (> 2-3mm in the body/tail)
  • Spectrum of presentations
  • NOT necessarily any of the following:
    • Chronic elevations in amylase/ lipase
    • Chronic abdominal pain with elevations in amylase/lipase
    • Acute relapsing pancreatitis – though this distinction is murky
    • Post-surgical exocrine dysfunction
    • Anyone with isolated steatorrhea
    • Swelling of the pancreatic head
65
Q

Chronic Pancreatitis

Etiologies

A
  • Mainly due to alcohol and tobacco
  • Metabolic (hypertriglyceridemia)
  • Long-standing obstruction of pancreatic duct by stones or neoplasms
  • Autoimmune pancreatitis
  • Hereditary pancreatitis (up to 25% of chronic pancreatitis)
  • Idiopathic causes
66
Q

Chronic Pancreatitis

Pathophysiology

A
  • Ductal obstruction hypothesis
    • Protein precipitates/calcifications in ducts ⇒ ⊕ trypsin ⇒ upstream inflammation/destruction
    • Apoptosis/fibrosis of upstream acini
  • Toxic/Metabolic hypothesis
    • Oxidative stress/free radicals from ETOH/CCK stimulation/smoking ⇒ stellate cell activation/fibrosis
  • Necrosis/Fibrosis hypothesis
    • Acute inflammatory attacks ⇒ necrosis/apoptosis
    • Cytokines from MΦ ⇒ chronic damage by converting to an anti-inflammatory fibrotic/”healing” state
    • Fibrosis ⇒ local ischemia ⇒ more necrosis/apoptosis
67
Q

Chronic Pancreatitis

Pathogenesis

A
  • Follows repeated episodes of acute pancreatitis
  • Initiates sequence of perilobular fibrosis, duct distortion, altered pancreatic secretions
  • Fibrogenic factors predominate
  • Including TGF-βand PDGF
  • Induce activation and proliferation of periacinar fibroblasts (pancreatic stellate cells)
  • Results in loss of pancreatic parenchyma and fibrosis
  • Special case: Autoimmune pancreatitis
    • Associated w/ presence of IgG4-secreting plasma cells in the pancreas
    • May respond to steroid therapy
68
Q

Chronic Pancreatitis
Appearance

A
  • Gross appearance
    • Firm gland, may see visibly dilated ducts, can contain calcified material
  • Microscopic
    • Loss of acini w/ relative sparing of islets (until late)
    • Variable duct obstruction
    • Duct dilation
    • Inspissated secretion in ducts ± calcification
    • Fibrosis
    • Variable chronic inflammation around lobules and ducts
69
Q

Chronic Pancreatitis

Diagnose

A

May be difficult to diagnose

  • Elevation of amylase may be compromised by loss of acinar cells
  • Look for jaundice and elevated alk phos w/ gallstones
  • Imaging may show calcifications
    • KUB (plain X-ray)
    • CT / MRCP (MRI)
    • Ultrasound
    • EUS (Endoscopic Ultrasound)
    • ERCP (Endoscopic RetroCholangioPancreatography)
  • Stool studies
  • Function tests (S-MRCP, secretin stimulation)
  • Ex lap with direct palpation
70
Q

Chronic Pancreatitis

Clinical Manifestations

A
  • Chronic pain
  • Pancreatic exocrine insufficiency
    • Steatorrhea
  • Chronic malabsorption
    • B12 deficiency
  • Diabetes
  • Biliary obstruction
  • Cancer
  • Pseudocysts (10%)
  • 20-25 year mortality rate of 50%
71
Q

Chronic Pancreatitis

Pain

A
  • Disabling
    • Often requires narcotics
    • Since pts often former ETOH, maybe neglected
  • Hard to detect, CT often negative for acute inflammation
    • Amylase and lipase can be low or normal
  • Causes: (plumbing and wiring)
    • Neural
    • Obstructed pancreatic duct with pancreatic stones
    • Malabsorption (cramps)
  • Management of chronic pancreatic pain:
    • High dose uncoated pancreatic enzymes
    • Quit ETOH and tobacco, lower Triglycerides, etc.
    • Neural modulators
    • Narcotics (use sparingly)
    • ERCP to remove pancreatic stones/dilate strictures
    • Surgery
72
Q

Chronic Pancreatitis

Steatorrhea/Exocrine Insufficiency

A
  • Happens at 90% destruction of pancreas – Nonlinear, cliff
  • Definition: > 7g fat/24hrs
  • Broad (extra-pancreatic) differential diagnosis
  • Sx have terrible sensitivity/specificity
    • Loose, oily stool, hard to flush, foul, ring in bowl, undigested pieces
  • Jejunum adapts (watch post-surgery closely)
    • Usually pts do not get dehydrated
  • Spot (qualitative) fecal fat, insensitive
  • Treatment: 40,000 IU coated lipase/meal
  • Complications: osteoporosis, vit A low, rarely low in vit K/E, magnesium
73
Q

Chronic Pancreatitis

Diabetes

A

“Thin, adult-onset insulin requiring”

“Type 3”

  • Development can indicate cancer even if no chronic pancreatitis
  • No glucagon or somatostatin, so hypoglycemia
  • Usually no ketoacidosis
  • Very insulin sensitive peripherally
  • Still, use metformin with insulin
74
Q

Chronic Pancreatitis

Cancer Risk

A
  • Sneaky in chronic pancreatitis (CP)
  • Most already have pain, worsening
  • Yet it is common
  • 4% lifetime risk (30-x ↑risk)
  • CP pts can get jaundiced from benign biliary obstruction of bile duct (intrapancreatic portion)
75
Q

Pancreatitis

Hereditary Factors

A
  • Recurrent attacks of severe acute pancreatitis can begin in childhood and result in chronic pancreatitis
  • Pts have 40% lifetime risk of pancreatic cancer
  • Shared feature: Defect that ↑ or sustains the activity of trypsin
  • Many genes, many mutations
    • PRSS1
      • Trypsinogen gene
      • See GOF mutations
      • Autosomal dominant
    • SPINK1
      • Encodes a trypsin inhibitor
      • See LOF mutations
      • Autosomal recessive
    • CFTR mutations seen in cystic fibrosis
76
Q

Cystic Fibrosis

Pancreas Effects

A
  • Viscous secretions
    • Due to abnormal electrolyte balance
  • Plug the ductal system (inspissation) ⇒ obstruction
  • Obstruction leads to inflammation (pancreatitis)
  • Most common autosomal recessive disorder in US Caucasians
  • In the US: major cause of pancreatic disease
77
Q

Non-neoplastic

Pancreatic Cysts

A
  • Congenital cyst
    • Anomalous development of pancreatic ducts results in unilocular thin-walled cysts
    • Up to 5cm in diameter
    • Sporadic or associated w/ AD Polycystic Kidney Disease or von Hippel-Lindau
  • Pseudocyst (75% of all pancreatic cysts)
    • Localized collection of necrotic and hemorrhagic debris lacking an epithelial lining
    • 2-30 cm diameter
    • Often follow acute pancreatitis, particularly if superimposed on chronic alcoholic pancreatitis
    • Can also follow trauma
78
Q

Pancreatic Neoplasms

A
  • Exocrine
    • Ductal adenocarcinoma (> 90 % of exocrine tumors)
    • Acinar cell carcinoma
    • Intraductal papillary mucinous tumor
    • Mucinous cystic neoplasm
    • Serous cystadenoma
    • Solid and Cystic Papillary Epithelial Neoplasm
    • Pancreatoblastoma
  • Pancreatic Endocrine Neoplasms
    • Neuroendocrine Tumors (Islet Cell Neoplasms)
79
Q

Cystic Pancreatic Neoplasms

A
  • Diverse group of tumors ranging from harmless benign cysts to precursors of cancer
  • Comprise 5-15% of cysts since most are pseudocysts
  • Comprise < 5% of all pancreatic neoplasms
  • Types:
    • Serous cystic neoplasms (serous cystadenomas)
      • Benign
      • 25% of all pancreatic cystic neoplasms
    • Mucinous Cystic Neoplasms
80
Q

Pancreatic

Mucinous Cystic Neoplasms

A
  • 95% in women
  • Usually slow growing mass in pancreatic tail
  • Filled w/ thick, tenacious mucin
  • Lined by columnar mucin-producing epithelium associated w/ dense ovarian-like stroma
  • Up to ⅓ of these masses show invasive adenocarcinoma upon resection; 50% of pts in this situation will die
  • Important to detect and treat before invasive cancer develops
81
Q

Pancreatic

Intraductal Papillary Mucinous Neoplasm (IPMN)

A
  • Mucin-producing neoplasm involving larger ducts
  • Seen more in men
  • Usually in head of pancreas
  • 10-20% are multifocal
  • No “ovarian” stroma
  • Can progress to invasive cancer so early detection is important
82
Q

Pancreatic

Solid-Pseudopapillary Neoplasm

A
  • Seen mainly in young women
  • Large, well circumscribed, malignant
    • Can grow very large
  • Associated w/ hyperactivation of Wnt signaling pathway
    • D/t acquired activating mutations of the CTNNB (Beta-catenin) oncogene
  • Surgery is often curative
83
Q

Pancreatic Intraepithelial Neoplasia (PanIN)

A
  • Lesion in small ducts
  • Believed to be the precursor to invasive pancreatic ductal carcinoma
    • Progression from non-neoplastic epithelium to PanIN to invasive carcinoma
    • Similar genetic and epigenetic alterations in PanIN and invasive CA
    • See PanIN adjacent to invasive CA
  • Epithelial cells in PanIN show dramatic telomere shortening
84
Q

Pancreatic Ductal Adenocarcinoma

Overview

A
  • Comprises the vast majority of pancreatic carcinomas (>90%)
  • # 4 cause of cancer death in US
  • Very high mortality rate
    • 5-year survival < 5%
  • Approximately 44,000 new cases in US in 2013
85
Q

Pancreatic Ductal Adenocarcinoma

Genetic Alterations

A
  • K-ras
    • Most frequently altered oncogene
    • Activating point mutations in 90-95% of cases
  • CDKN2A
    • Inactivated in 95% of cases
    • Tumor suppressor gene
  • SMAD4
    • Inactivated in 55% of cases
    • Tumor suppressor gene
  • TP53
    • Inactivated in 70-75% of cases
    • Encodes p53
    • Tumor suppressor gene
  • Other chromosome alterations
  • DNA methylation abnormalities
  • Abnormal gene expression pathways
86
Q

Pancreatic Ductal Adenocarcinoma
Epidemiology

A
  • 80% of cases occur at ages 60-80
  • More blacks than whites
  • Strongest environmental link: cigarette smoking
  • Less certain
    • Consumption of diet rich in fats
    • Chronic pancreatitis, DM
    • Familial clustering is seen
      • Germline BRCA2 mutation in 10% of pancreatic CA cases in Ashkenazi Jews
      • Some families show germline mutations in CDKN2A
        • Pancreatic cancer and melanoma
87
Q

Pancreatic Ductal Adenocarcinoma

Apperance

A
  • Gross:
    • Location:
      • Head (60%)
        • Tumors obstruct distal common bile duct early
        • Causes distention of biliary tree, many pts develop jaundice
      • Body (15%)
        • Carcinomas here and in tail remain silent until large and often disseminated
      • Tail 5%
      • Diffuse 20%
    • Morphology:
      • Gray-white color
        • Stands out from normal yellowish/tan pancreatic parenchyma
      • Firm/hard
        • Due to desmoplastic reaction
        • Proliferation of fibroblasts surrounding malignant cells and glands
        • Mass or diffuse replacement of pancreas
  • Microscopic:
    • Moderately to poorly differentiated adenocarcinoma
    • Aggressive and deeply infiltrative
    • Elicits an intense desmoplastic reaction
      • Can make it difficult to distinguish from chronic pancreatitis at times
        • Both show glands surrounded by fibrosis
88
Q

Pancreatic Ductal Adenocarcinoma

Clinical Characteristics

A
  • Presentation:
    • Often silent until invades adjacent structures
    • Pain
    • Jaundice (sometimes before pain)
    • Pruritis
    • Pancreatitis
    • Peripheral fat necrosis
    • Migratory thrombophlebitis (Trousseau sign)
  • < 20% of cases are resectable at dx
  • Have invaded vessels and other structures or metastasized widely
  • No effective screening technique
89
Q

Pancreatic

Acinar Cell Carcinoma

A
  • Rare tumor
  • Peak: 5th-8th decade
  • Usually large w/ foci of necrosis
  • Shows acinar arrangement of cells
    • Reminiscent of normal pancreatic acini
  • Contain zymogen granules
  • May be associated w/ peripheral fat necrosis and polyarthralgias (15% of pts)
90
Q

Pancreatoblastoma

A
  • Rare neoplasm
  • Mainly seen in children ages 1-15
  • Malignant, but better survival than pancreatic ductal CA
91
Q

Pancreatic Neuroendocrine Tumors (PanNETs)

Overview

A
  • Comprise about 2% of pancreatic neoplasms
  • Tumors can be sporadic or MEN I-associated
  • May be functional (produces active hormone) or non-functional
  • May be single or multiple; benign or malignant
  • Difficult to predict behavior based on LM appearance
  • Criteria for malignancy are metastases, vascular invasion, infiltration of other tissues
  • 90% of tumors producing insulin are benign
  • 60-90% of other neuroendocrine tumors are malignant
92
Q

PanNETs

Genetic Alterations

A
  • MEN1 gene
    • Causes MEN1 syndrome
    • Often altered in sporadic neuroendocrine tumors
  • LOF mutations in tumor suppressor genes PTEN and TSC2
    • Results in activation of mTOR signaling pathway
  • Inactivating mutations in two genes:
    • ATRX
      • Alpha-thalassemia/mental retardation syndrome (X-linked)
    • DAXX
      • Death-domain associated protein
93
Q

Insulinoma

A
  • Beta-cell tumor (insulinoma)
    • Most common PanNET
  • Hyperinsulinism ⇒ may induce clinically significant hypoglycemia
    • See confusion, sweating, palpitations, stupor, LOC
    • Episodes precipitated by fasting or exercise
    • Relieved by feeding or giving glucose
  • Gross: Usually benign, solitary, often < 2 cm, reddish-brown
  • Micro: look like islet cells, not much dysplasia
    • May contain amyloid
94
Q

Zollinger Ellison Syndrome

A
  • Gastrin producing islet cell tumor
    • 2nd most common pancreatic endocrine neoplasm (PanNET)
  • Results in:
    • Parietal cell hyperplasia
    • ↑ HCl secretion
    • Peptic ulcers
  • Tumor can also arise in duodenum or peripancreatic soft tissue
  • Majority are malignant
    • May have metastasized at time of presentation
  • May be a component of MEN1 syndrome (often multifocal in this case)

6. HDS GI Repro (30 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions