Chapter 18/19: Gallbladder and Pancreas Flashcards
- What is the gallbladder?
- Epithelium?
- 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
What is the most common congenital anomaly of the gallbladder?
- Inward folded fundus –> Phrygian cap
Is agenesis of ANY part of the GB, bile duct, or biliary atresia lethal?
No.
More than 95% of biliary tract disease is attributable to __________, which most often lodge at what side
- Cholelithiasis (gallstones).
- Infudibulum (Hartmans pound)
Who is more likely to get gallstones (cholelithiasis)?
- Family History
- Fair skin (white)
- Fat (obsese)
- Female
- Forties
- Fertile (d/t estrogen; thus, pregnant or taking oral contraceptives)
What are the 2 types of gallstones and who are they most common in?
-
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)
Why is estrogen exposure a risk factor for the development of gallstones?
Because of this who is at the most risk?
- Increases expression of: hepatic lipoprotein receptors and hepatic HMG-CoA reductase activity —> enhanced cholesterol uptake and biosynthesis
- Females taking OCs and during pregnancy
What infections are comon causes of pigment stones?
- Clinorchis sinensis (Liver fluke)
- Ascaris lumbricoides (intestinal nematode = roundwork parasites)
- E. coli
Rates of cholesteorl gallstones approach 75% in persons of which cultural group?
Native Americans of the Pima, Hopi, and Navajo groups
Cholesterol Stones
- Found where?
- Composed of/color?
- 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
- Pure = yellow, granular, hard and round
Pigment Stones
- Color?
- Location
- 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
-
Black => sterile bile ducts (oxidized polymers of Ca2+ salts of unconjugated bilirubin, salts and mucin); friable, spikey
Can Cholesterol stones be seen on XR?
- If made largely of cholesterol = radioluscent (NO)
- If enough calcium carbonate = radiopaque (YES)
Can black and brown pigmented stones be seen on X-ray?
- 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
The development of pigment stones is associated with disorders that cause an ↑ in what?
List some of these disorders
- Unconjugated bilirubin
- Chronic hemolytic anemias = increases unconj bilirubin
- Severe ileal dysfunction or bypass
- Cirrhosis/liver disease
- Bacterial infection biliary tree
How does the size of the gallstone relate to the likelihood of it causing problems?
- 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
What are complications that may arise sometimes with large gallstones?
- May erode directly into an adjacent loop of small bowel, generating an intestinal obstruction
- “Gallstone ileus” or “Bouveret syndrome”
What are symptoms of gallstones?
Main complication that it can lead to?
- Most = asymptomatic.
- Biliary colic (excuciating, constant pain) in the RUQ => radiates to right upper shoulder or work & worse after a fatty meal.
- Acute cholecystitis
Clinical pearl: if an older person has gallstones, what should we suscept?
Cancer; bc rare in this demographic
What is the primary complication of gallstones and the most common reason for emergency cholecystectomy?
Acute calculous cholecystitis
What is acute calculous cholecystitis?
- 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
What is acute acalculous cholecystitis?
- Occurs in severely ill patients due to ischemia d.t cystic artery.
Acute calculous cholecystitis is more common in who?
DM wiith symptomatic gallstones.
Acute Acalculous Cholecystitis most frequently occurs in patients who are hospitalized for unrelated conditions, such as (list 5 common settings)?
- Sepsis w/ hypotension and multisystem organ failure
- Immunosuppression
- Major trauma and burns
- Diabetes mellitus
- Infections
- In the acute cholecystitis, the GB is enlarged and the serosal covering is covered by ________
- When the exudate inside the gallbladder lumen is virtually pure pus, the condition is referred to as?
- 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?
- Invasion of the GB w/ gas-forming organisms, such as clostridia and coliforms, may cause a condition known as?
- Fibrinopurulent exudate
- Gallbladder empyema
- Gangrenous cholecystitis
- Acute “emphysematous” cholecystitis
How does acute calculous cholecystitis typically present clinically?
Associated sx’s?
- Progressive RUQ or epigastric pain lasting for >6 hours
- Mild fever, anorexia, tachycardia, sweating
- NO jaundice.
- Leukocytosis (L-shift) and Increae in ALP
In patients experiencing symptoms of acute cholecystitis, it is important to rule out what?
MI (bc will have epigastric pain + tachycardia + sweating); so think MI until proven otherise.
Presence of hyperbilirubinemia/jaundice in a patient presenting w/ suspected acute calculous cholecystitis suggests what kind of obstruction?
Obstruction of common bile duct
In 90% of cases Chronic Cholecystitis is associated with?
In 33% of cases which 2 organisms may be culutred from the bile?
- 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.
In some cases of Chronic Cholecystitis, what is a sign we can see on XR and what does this allude to?
Porcelain GB (dystrophic calcification)=> increase risk for CANCER
Which of the following is the most common
malignancy of the gallbladder?
A. Sarcoma
B. Lymphoma
C. Squamous cell carcinoma
D. Adenocarcinoma
E. Metastasis
D. Adenocarcinoma (bc columnar cells(
In Chronic Cholecystitis, what does the serosa look like?
- Wall
- Lumen
- Mucosa
- 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
*
Outpuchings of the mucosal epithelium through the wall of the GB may be quite prominent in Chronic Cholecystitis and is known as?
Rokitansky-Aschoff sinuses
What is seen in Xanthogranulomatous cholecystitis is triggered by _________.
Describe the morphology.
Characteristic cell type?
- 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)
Chronic cholecystitis does not have the striking clinical manifestations of acute forms and is usually characterized by what symptoms?
- Recurrent attacks of either steady epigastric or RUQ pain
- N/V and intolerance for fatty foods are common findings
What is the most common malignancy of the extrahepatic biliary tree?
GB Adenocarcinoma
-
Occurs after chronic inflammation of the GB
- => Chronic cholestystitis (porcelain GB)
- => Chronic Salmonella S.typi infection
GB Adenoarcinoma
- More common in who?
- Which areas in the world have highest risk?
- Most important risk factor?
- 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)
- By the time GB adenocarcinoma is discovered, they have done what?
- MC sites of seeding?
- Invaded liver => extend into cystic duct, adjacent bile ducts and portal hepatic LN.
- Peritoneum, GI tract, lungs via celiac plexus
Why are carcinomas of the GB typically of poor prognosis?
- Typically are detected late
- Presenting sx’s are indistinguishable from those associated with cholelithiasis
What is the exocrine pancreas?
- 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
What is the most common congenital anomaly of the pancreas?
What occurs embryologically?
- - Pancreas Divisum
- Failure of fusion ventral and dorsal buds
- => Pancreatic secretions mainly through small caliber, minor papilla instead of papila of vater.
- Failure of fusion ventral and dorsal buds
Pancreas Divisum predisposes ppl to _________.
Chronic pancreatiis
Annular pancreas is caused by what?
Can lead to what complication?
- Abnormal rotation: A band-like ring of normal pancreatic tissue completely encircles the 2nd portion of the duodenum => SBO
- Ectopic pancreas is usually asymp, but can lead to pain from inflammation and _________. Most common where?
Mucosal bleeding
- Stomach
- Duodenum
- Jejunum
- Meckels
- Ileum
What is acute pancreatitis?
-
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
What are the most common causes of acute pancreatitis?
- If Male = alcohol
- occurs at a younger age
- If Female = gallstones in CBD
- occurs at older age
Clinically, what does Acute Pancreatitis look like?
Diagnosed?
- 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
In patients with acute pancreatitis, serum lipase levels will be _____.
3-4x more than NL
Rare signs of DANGEROUS acute pancreatitis?
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
choledocholithiasis.
CBD bile duct stones; => biliar obsttrucion => backs up in liver
=> jaundice
=> increase in ALP > AST/ALT
=> lad to cholangitis
Pathogenesis of acute pancreatitis
-
+ pancreatic enzymes (TRYPSIN) => destroy pancreatic tissue and cause autoimmflammatory reaction
- Inflammation and edem
- Proteolysis
- Fat necrosis
- Damage to vessel wall and hemorrhage
- => acute pancreatitis
What type of necrosis can occur in acute pancreatitis?
-
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.
How do low Ca2+ levels vs. high Ca2+ levels have an affect on trypsin?
- High Ca2+ –> loss of autoinhibition = trypsin activation
- Low Ca2+ –> trypsin cleaves and inactivates itself = inactivation
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
What medications can cause Acute Pancreatitis?
- furosemide, azathioprine, estrogens, etc.
What is hereditary pancreatitis?
- Recurrent attacks of severe acute pancreatitis and ultimately leading to chronic pancreatitis caused by a defect that increases or sustains the activity of trypsin
Causes of hereditary pancreatitis?
Mutations in
- CFTR (thus ppl with CF are at high risk)
- SPINK1
Which 3 metabolic disorders are implicated in the development of acute pancreatitis?
- Hypertriglyceridemia
- Hypercalcemic states
- Hyperparathyroidism –> increased Ca2+
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?
- 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
How does acute vs. chronic pancreatitis differ in the type of injury that occurs to the pancreatic parenchyma (ie., reversible or irreversible)
- Acute is associated with reversible injury
- Chronic is associated with irreversible injury
What is chronic pancreatitis?
- MC seen in?
- MCCause?
- 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.
*
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?
- Production of fibrogenic inflammatory mediators TGFβ and PDGF
- => + and proliferation of periacinar myofibroblasts (pancreatic stellate cells) => deposit collagen and fibrosis
Chronic pancreatitis is hard to distinguish from __________. Why?
Pancreatic cancer bc both cause fibrosis
Chronic pancreatitis may present in many different ways, such as?
May be precipitated by?
- Typically, clinically silent, but there may be recurrent attacks of epigastric pain and/or jaundice
- Persistent back pain
- Pseudocysts
- Attacks may be precipated by alcohol abuse, overeating, or the use of opioids + other drugs
In some patients, chronic pancreatitis may be clinically silent until the development of what?
- 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)
- Pancreatic insufficiency –> loss of exocrine/endrocinr fx => pancrease burnt TF out
Diagnosis of chronic pancreatitis requires a high degree of suspicion, but which finding on CT and ultrasound can be very helpful?
- Calcifications with pancreas
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)
- 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
- 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?
- Infiltrating ductal adenocarcinoma, more common at HEAD of cancer
- Smoking (2x risk)
- Ashkanazi Jews and African American
How does tumor location affect presentation?
-
60% = head of the gland.
- Obstruct distal common bile duct => increase in direct bilirubin and ALP=> obsructivepainless jaundice
- 15%: body of pancrease
- Clinically silent body and tail do not impinge structures
- When discovered, large and disseminated.
*
Why are pancreatic cancer so deadly?
Remain silent until 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
Symptoms of Pancreatic Carcinoma
- 1st => pain, but by the time htis happens, often incurable
- Obstructive jaundice (head of pancrease)
- WL/anorexia, malaise, weakness => advanced
Most pancreas cancers are __________ and incite a what charactersitic reaction
Most pancreas cancers are adenocarcinomas (columnar cells wiith glands) and incite a dense desmoplastic reaction => dense stromal fibrosis (=> hard and hard to dx)
Invasive pancreatic cancers are believed to arise from which well-defined noninvasive precursor lesions in small ducts?
Pancreatic intraepithelial neoplasia (PanIN)
Which is the most frequently altered oncogene in pancreatic cancer?
KRAS
Tumor supressor genes and DNA repair are seen in pancreatic adenocarcinoma
- p16/CDKN21
- TP53
-
SMAD4 ***
- => important for TGF-b signaling
- Which disorder is associated with the highest increased risk (130-fold) for the development of pancreatic cancer?
Peutz-Jegers syndrome
Other disorders associated with the increased risk for the development of pancreatic cancer?
- Hereditary pancreatitic
- Melanoma
- Strong family history
- Hereditary breast and ovarian cancer
- HNPCC
Which “sign” is seen in a small % of patients with pancreatic cancer?
Migratory thrombophlebitis or the Trousseau sign => redness and induration on the skin that migrates
