Chapter 18/19: Gallbladder and Pancreas

Question 1

• What is the gallbladder?
• Epithelium?

Answer 1

• Between meals, bile is stored and concentrated in the gallbladder.
• When fat is sensed, CCK is released and causes GB to contract, releasing bile.
• Columnar epithelium

Question 2

What is the most common congenital anomaly of the gallbladder?

Answer 2

• Inward folded fundus –> Phrygian cap

Question 3

Is agenesis of ANY part of the GB, bile duct, or biliary atresia lethal?

Answer 3

No.

Question 4

More than 95% of biliary tract disease is attributable to __________, which most often lodge at what side

Answer 4

• Cholelithiasis (gallstones).
• Infudibulum (Hartmans pound)

Question 5

Who is more likely to get gallstones (cholelithiasis)?

Answer 5

1. Family History
2. Fair skin (white)
3. Fat (obsese)
4. Female
5. Forties
6. Fertile (d/t estrogen; thus, pregnant or taking oral contraceptives)

Question 6

What are the 2 types of gallstones and who are they most common in?

Answer 6

• Cholesterol stones (factors that increase in cholestrol)
  
  • MC: Developed countries due to diet
• Pigment stones (bilirubin)
  
  • MC: Developing countries due to infections or bleeding (chronic hemolytic syndrome)

Question 7

Why is estrogen exposure a risk factor for the development of gallstones?

Because of this who is at the most risk?

Answer 7

• Increases expression of: hepatic lipoprotein receptors and hepatic HMG-CoA reductase activity —> enhanced cholesterol uptake and biosynthesis
• Females taking OCs and during pregnancy

Question 8

What infections are comon causes of pigment stones?

Answer 8

1. Clinorchis sinensis (Liver fluke)
2. Ascaris lumbricoides (intestinal nematode = roundwork parasites)
3. E. coli

Question 9

Rates of cholesteorl gallstones approach 75% in persons of which cultural group?

Answer 9

Native Americans of the Pima, Hopi, and Navajo groups

Question 10

Cholesterol Stones

• Found where?
• Composed of/color?

Answer 10

• ONLY gallbladder
• 100% cholesterol (pure/rare) => 50% cholesterol
  
  • Pure = yellow, granular, hard and round
    
    • On transection look like a crystalline palisade
  • As ↑ calcium carbonate, bilirubin, phosphates = black

Question 11

Pigment Stones

• Color?
• Location

Answer 11

• Black => Brown
  
  • Black => sterile bile ducts (oxidized polymers of Ca2+ salts of unconjugated bilirubin, salts and mucin); friable, spikey
    
    • Rarely bigger than 1.5 cm; more present
  • Brown => infected large bile ducts (same comp + cholesterol); soap-like, greasy and shiny

Question 12

Can Cholesterol stones be seen on XR?

Answer 12

• If made largely of cholesterol = radioluscent (NO)
• If enough calcium carbonate = radiopaque (YES)

Question 13

Can black and brown pigmented stones be seen on X-ray?

Answer 13

• Majority of black stones are radiopaque = can see on XR (due to calcium salts)
• Brown stones are radiolucent (can’t be seen) due to calcium soaps

Question 14

The development of pigment stones is associated with disorders that cause an ↑ in what?

List some of these disorders

Answer 14

1. • Unconjugated bilirubin
2. • Chronic hemolytic anemias = increases unconj bilirubin
3. • Severe ileal dysfunction or bypass
4. • Cirrhosis/liver disease
5. • Bacterial infection biliary tree

Question 15

How does the size of the gallstone relate to the likelihood of it causing problems?

Answer 15

• Larger the calculi, the less likely they are to enter the cystic or common ducts to produce obstruction
• Very small stones, or “gravel,” are far more dangerous

Question 16

What are complications that may arise sometimes with large gallstones?

Answer 16

• May erode directly into an adjacent loop of small bowel, generating an intestinal obstruction
• “Gallstone ileus” or “Bouveret syndrome”

Question 17

What are symptoms of gallstones?

Main complication that it can lead to?

Answer 17

• Most = asymptomatic.
• Biliary colic (excuciating, constant pain) in the RUQ => radiates to right upper shoulder or work & worse after a fatty meal.
• Acute cholecystitis

Question 18

Clinical pearl: if an older person has gallstones, what should we suscept?

Answer 18

Cancer; bc rare in this demographic

Question 19

What is the primary complication of gallstones and the most common reason for emergency cholecystectomy?

Answer 19

Acute calculous cholecystitis

Question 20

What is acute calculous cholecystitis?

Answer 20

• Inflammation of the GB due to (90%) an obstruction caused by a stone in the cystic duct or neck, due to chemical irritation and inflammation, which causes dilation of GB => increased intraluminal pressure => disrupt blood flow.
  
  • no bacterial infection causes these changes, but can occur later

Question 21

What is acute acalculous cholecystitis?

Answer 21

• Occurs in severely ill patients due to ischemia d.t cystic artery.

Question 22

Acute calculous cholecystitis is more common in who?

Answer 22

DM wiith symptomatic gallstones.

Question 23

Acute Acalculous Cholecystitis most frequently occurs in patients who are hospitalized for unrelated conditions, such as (list 5 common settings)?

Answer 23

1. • Sepsis w/ hypotension and multisystem organ failure
2. • Immunosuppression
3. • Major trauma and burns
4. • Diabetes mellitus
5. • Infections

Question 24

1. In the acute cholecystitis, the GB is enlarged and the serosal covering is covered by ________
2. When the exudate inside the gallbladder lumen is virtually pure pus, the condition is referred to as?
3. In severe cases of acute cholecystitis the GB may be transformed into a green-black necrotic organ w/ small-to-large perforations and this condition is known as?
4. Invasion of the GB w/ gas-forming organisms, such as clostridia and coliforms, may cause a condition known as?

Answer 24

1. Fibrinopurulent exudate
2. Gallbladder empyema
3. Gangrenous cholecystitis
4. Acute “emphysematous” cholecystitis

Question 25

How does **acute calculous cholecystitis** typically present clinically? Associated sx's?

Answer 25

* - Progressive RUQ or epigastric pain lasting for \>6 hours * - Mild fever, anorexia, tachycardia, sweating * - NO jaundice. * - Leukocytosis (L-shift) and Increae in ALP

Question 26

In patients experiencing symptoms of acute cholecystitis, it is important to rule out what?

Answer 26

**MI** (bc will have epigastric pain + tachycardia + sweating); so think MI until proven otherise.

Question 27

Presence of **hyperbilirubinemia/jaundice** in a patient presenting w/ suspected acute calculous cholecystitis suggests what kind of obstruction?

Answer 27

**Obstruction of common bile duct**

Question 28

In 90% of cases **Chronic Cholecystitis** is associated with? In 33% of cases which 2 organisms may be culutred from the bile?

Answer 28

- 90% : **cholelithiasis** (gallstones) - 33%: **E. coli** and **enterococci** Can be a be a sequel to repeated episodes of mild to severe acute cholecystitis, but in many instances it develops in the apparent absence of antecedent attacks.

Question 29

In some cases of **Chronic Cholecystitis**, what is a sign we can see on XR and what does this allude to?

Answer 29

**Porcelain GB (dystrophic calcification)=\> increase risk for _CANCER_**

Question 30

Which of the following is the most common malignancy of the gallbladder? A. Sarcoma B. Lymphoma C. Squamous cell carcinoma D. Adenocarcinoma E. Metastasis

Answer 30

**D. Adenocarcinoma (bc columnar cells(**

Question 31

In **Chronic Cholecystitis,** what does the serosa look like? * Wall * Lumen * Mucosa

Answer 31

* The serosa is typically smooth and glistening, but may be dulled by **subserosal fibrosis** * ​Wall = thick, gray and white * Lumen = green, yellow mucoid bile with stones * Mucosa = preserved *

Question 32

**Outpuchings of the mucosal epithelium** **through** the **wall** of the GB may be quite prominent in Chronic Cholecystitis and is known as?

Answer 32

Rokitansky-Aschoff sinuses

Question 33

What is seen in Xanthogranulomatous cholecystitis is triggered by \_\_\_\_\_\_\_\_\_. Describe the morphology. Characteristic cell type?

Answer 33

- **Rupture of Rokitansky-Aschoff sinuses** into the wall of the GB --\> accumulation of MO that have ingested bilirary phospholipids - GB has THICC and is shrunken, nodular, and chronically inflammed w/ necrosis + hemorrhage - Xanthoma cells are **MO w/ ingested biliary phospholipids** (foamy cytoplasm = lipids in cytoplasm)

Question 34

**Chronic cholecystitis** does not have the striking clinical manifestations of acute forms and is usually characterized by what symptoms?

Answer 34

**- Recurrent attacks** of either steady epigastric or RUQ pain - N/V and intolerance for fatty foods are common findings

Question 35

What is the most common malignancy of the extrahepatic biliary tree?

Answer 35

**GB Adenocarcinoma** * **Occurs after chronic inflammation of the GB** * **​=\> Chronic cholestystitis (porcelain GB)** * **=\> Chronic Salmonella S.typi infection**

Question 36

**GB Adenoarcinoma** * More common in who? * Which areas in the world have highest risk? * Most important risk factor?

Answer 36

* **Females** * **Chile, Bolivia, North India** * Besides gener and ethnicity, **gallstones** (found in 95% of cases but only 1-2% of ppl with gallstones get cancer)

Question 37

* By the time GB adenocarcinoma is discovered, they have done what? * MC sites of seeding?

Answer 37

* Invaded liver =\> extend into cystic duct, adjacent bile ducts and portal hepatic LN. * Peritoneum, GI tract, lungs via celiac plexus

Question 38

Why are carcinomas of the GB typically of poor prognosis?

Answer 38

* - Typically are detected late * - Presenting sx's are indistinguishable from those associated with cholelithiasis

Question 39

What is the **exocrine pancreas?**

Answer 39

* Exocrine pancreas = 80-85% of pancreas and is made of acinar cells that secrete enzymes needed for digestion: trypsinogen, chymotrypisnogen, procarboxypeptidase, proelastase, kallikreinogen and phospholaipase A &B

Question 40

What is the most common congenital anomaly of the pancreas? What occurs embryologically?

Answer 40

* **- Pancreas Divisum** * - Failure of fusion ventral and dorsal buds * =\> Pancreatic secretions mainly through small caliber, minor papilla instead of papila of vater.

Question 41

**Pancreas Divisum** predisposes ppl to **\_\_\_\_\_\_\_\_\_.**

Answer 41

**Chronic pancreatiis**

Question 42

**Annular pancreas** is caused by what? Can lead to what complication?

Answer 42

* - Abnormal rotation: A band-like ring of normal pancreatic tissue completely encircles the 2nd portion of the duodenum =\> **SBO**

Question 43

* **Ectopic pancreas** is usually asymp, but can lead to pain from inflammation and \_\_\_\_\_\_\_\_\_. Most common where?

Answer 43

**_Mucosal bleeding_** 1. **Stomach** 2. **Duodenum** 3. Jejunum 4. Meckels 5. Ileum

Question 44

What is acute pancreatitis?

Answer 44

* **Reversible** injury to parenchyma of pancreas associated with inflammation caused when block flow of enzymes, however the pancreas is still making them. Large amounts of + trypsin =\> + more typsin and other pancreatic enzymes =\> autodestFUCK =\> self-perpetuating * =\> **liquifactive necrosis** and **hemorrhage** if untx

Question 45

What are the most common causes of **acute pancreatitis?**

Answer 45

* If **Male** = **alcohol** * occurs at a younger age * If **Female** = **gallstones** in CBD * occurs at older age

Question 46

Clinically, what does Acute Pancreatitis look like? Diagnosed?

Answer 46

* SX * Constant epigastric =\> upper back or **L shoulder** “boring” * **Anorexia, N/V** * * **Labs** * ↑ **amylase** (24 hours), * ↑ **lipase** (72-96 hours)\*\*\* * 10% **glycosuria** * **Hypocalcemia** due to deposition of Ca⁺⁺ soap formation in necrotic fat (saponification) * If caused by gallstones = ABNL LFTs * ↑ ALP\>\> AST/ALT * ↑ Conjugated Billirubin * ↑ WBC (leukocytosis * Dx: CT

Question 47

In patients with acute pancreatitis, serum lipase levels will be \_\_\_\_\_.

Answer 47

**3-4x more than NL**

Question 48

Rare signs of **DANGEROUS acute pancreatitis?**

Answer 48

Cullens signs = periumbilical ecchymosis Grey Turner sign = ecchymosis in flank D/t spread of **fat necrosis** and **inflammation/hemorrage** from damage d/t pancreatic enzymes with retroperitoneal or **intraabdominal bleeding.** **= high morality bc indic severe**

Question 49

choledocholithiasis.

Answer 49

CBD bile duct stones; =\> biliar obsttrucion =\> backs up in liver =\> jaundice =\> increase in ALP \> AST/ALT =\> lad to cholangitis

Question 50

**Pathogenesis of acute pancreatitis**

Answer 50

* **+ pancreatic enzymes (TRYPSIN)** =\> destroy pancreatic tissue and cause autoimmflammatory reaction * Inflammation and edem * Proteolysis * Fat necrosis * Damage to vessel wall and hemorrhage * **=\> acute pancreatitis**

Question 51

***What type of necrosis can occur in acute pancreatitis?***

Answer 51

* **Fat necrosis** =\> occurs when inflammation spreads to involve fat surrounding pancreas, leading to hypocalcemia and hypomagnesia. * Lipase =\> release FFA =\> bind Ca2+ =\> saponification * Indicates **POOR prognosis** of acute pancreatitis.

Question 52

How do low Ca2+ levels vs. high Ca2+ levels have an affect on trypsin?

Answer 52

- **High Ca2+** --\> loss of autoinhibition = t**rypsin activation** - Low Ca2+ --\> trypsin cleaves and inactivates itself = inactivation

Question 53

How does **primary acinar cell injury play** a role in the pathogenesis of acute pancreatitis? i.e., role of oxidative stress, what's activated and which TF's expressed

Question 54

What medications can cause Acute Pancreatitis?

Answer 54

* furosemide, azathioprine, estrogens, etc.

Question 55

What is hereditary pancreatitis?

Answer 55

* Recurrent attacks of severe acute pancreatitis and ultimately leading to chronic pancreatitis caused by a defect that increases or sustains the activity of **trypsin**

Question 56

Causes of **hereditary pancreatitis?**

Answer 56

Mutations in * **CFTR** (thus ppl with CF are at high risk) * **SPINK1**

Question 57

Which 3 metabolic disorders are implicated in the development of acute pancreatitis?

Answer 57

1. Hypertriglyceridemia 2. Hypercalcemic states 3. Hyperparathyroidism --\> increased Ca2+

Question 58

**Full-blown acute pancreatitis** is a medical emergency and how does it typically manifest clinically? What causes the serious systemic complications and what are these complications that may be seen?

Answer 58

* - Sudden disasterous onset of "acute abdomen" * - Release of toxic enzymes, cytokines, and other mediators into circulation -\> systemic inflammatory response (leukocytosis, DIC, edema, and acute respiratory distress syndrome) * - Shock and acute renal tubular necrosis may occur

Question 59

How does acute vs. chronic pancreatitis differ in the type of injury that occurs to the pancreatic parenchyma (ie., reversible or irreversible)

Answer 59

- **Acute** is associated with **reversible injury** - **Chronic** is associated with **irreversible injury**

Question 60

What is **chronic pancreatitis?** * - MC seen in? * - MCCause?

Answer 60

* Prolonged recurrent bouts of inflammation=\> ***_irreversible_*** destruction of exocrine parenchyma, fibrosis/calcification and, eventually, the endocrine parenchyma * Middle aged males * Adults =\> Long term alcohol acbuse * Kids =\> Cystic fibrosis * \*\*\*\*many causes of AP are not recurrent, these are. *

Question 61

While many of the cytokines produced during acute and chronic pancreatitis are similar, which type tends to predominate in **chronic pancreatitis?** Leads to activation of?

Answer 61

* Production of **fibrogenic** inflammatory mediators **TGFβ and PDGF** * =\> + and proliferation of **periacinar myofibroblasts (pancreatic stellate cells)** =\> deposit **collagen** and **fibrosis**

Question 62

Chronic pancreatitis is hard to distinguish from \_\_\_\_\_\_\_\_\_\_. Why?

Answer 62

Pancreatic cancer bc both cause fibrosis

Question 63

**Chronic pancreatitis** may present in many different ways, such as? May be precipitated by?

Answer 63

1. Typically, clinically silent, but there may be **recurrent attacks of epigastric pain and/or jaundice** 2. Persistent back pain 3. Pseudocysts * Attacks may be precipated by alcohol abuse, overeating, or the use of opioids + other drugs

Question 64

In some patients, ***chronic pancreatitis*** may be clinically silent until the development of what?

Answer 64

1. - Pancreatic insufficiency --\> loss of exocrine/endrocinr fx =\> pancrease burnt TF out 1. steatorrhea 2. - Diabetes mellitus (due to destruction of exocrine and endocrine pancrease = \> loss of insulin)

Question 65

Diagnosis of **chronic pancreatitis** requires a high degree of suspicion, but which finding on CT and ultrasound can be very helpful?

Answer 65

1. **Calcifications with pancreas**

Question 66

A variety of cysts can arise in the pancreas. Most are nonneoplastic pseudocysts, but congenital cysts and neoplastic cysts also occur **What are the most common pancreatic cysts (75% of patients)**

Answer 66

* Pseudocysts= walled off collections of necrotic and hemorrhagic material rich in pancreatic enzymes enveloped by fibrous and granulation tissue of fat necrosis that lack an epithelial lining (hence "pseudo"). * Occur after: bout of acute pancreatitis, particularly one superimposed on chronic alcoholic pancreatitis or trauma

Question 67

* **Pancreatic carcinoma** = ___________ is the 4th leading cause of death and one of the most aggressive solid malignancies (\<5% of survival) * Strongest risk factor: \_\_\_\_\_\_\_\_\_\_\_\_ * More common in what race?

Answer 67

* **Infiltrating ductal adenocarcinoma, more common at HEAD of cancer** * **Smoking (2x risk)** * **Ashkanazi Jews and African American**

Question 68

How does tumor location affect presentation?

Answer 68

* **60%** = **head of the gland.** * Obstruct distal common bile duct =\> increase in direct bilirubin and ALP=\> **obsructive****painless jaundice** * 15%: body of pancrease * Clinically silent body and tail do not impinge structures * When discovered, large and disseminated. *

Question 69

Why are **pancreatic cancer** so deadly?

Answer 69

**Remain silent u**ntil they invade into adjacent structures . - **Pain** is usually the 1st symptom, but by this time the cancer is usually beyond cure - Weight loss, anorexia, and generalized malaise = cachexia = advanced disease

Question 70

Symptoms of Pancreatic Carcinoma

Answer 70

* 1st =\> pain, but by the time htis happens, often incurable * Obstructive jaundice (head of pancrease) * - WL/anorexia, malaise, weakness =\> advanced

Question 71

Most **pancreas cancers** are __________ and incite a what charactersitic reaction

Answer 71

Most pancreas cancers are **adenocarcinomas** (columnar cells wiith glands) and incite a **dense desmoplastic reaction =\> dense stromal fibrosis** **(=\> hard and hard to dx)**

Question 72

Invasive pancreatic cancers are believed to arise from which well-defined noninvasive **precursor lesions** in small ducts?

Answer 72

**Pancreatic intraepithelial neoplasia (PanIN)**

Question 73

Which is the most frequently altered **oncogene** in pancreatic cancer?

Answer 73

KRAS

Question 74

Tumor supressor genes and DNA repair are seen in pancreatic adenocarcinoma

Answer 74

1. p16/CDKN21 2. TP53 3. **SMAD4 \*\*\*** 1. **=\> important for TGF-b signaling**

Question 75

1. Which disorder is associated with the **highest increased risk** (130-fold) for the development of **pancreatic cancer?**

Answer 75

**Peutz-Jegers syndrome**

Question 76

Other disorders associated with the increased risk for the development of **pancreatic cancer?**

Answer 76

1. **Hereditary pancreatitic** 2. **Melanoma** 3. **Strong family history** 4. **Hereditary breast and ovarian cancer** 5. **HNPCC**

Question 77

Which "sign" is seen in a small % of patients with **pancreatic cancer?**

Answer 77

**Migratory thrombophlebitis** or the **Trousseau sign =\> redness and induration on the skin that migrates**