Pancreatic, biliary tree, and salivary diseases Flashcards
Describe the normal pancreas and it’s anatomical location
- Lobulated organ situated posterior to the stomach and anterior to the thoracic spine and ribs
- Retroperitoneal structure
- Traverses abdomen from left to right infero-diagonally, with the tail situated immediately medial to the splenic hilum and the head sandwiched within the C-loop of the duodenum
- Blood supply is dereived from branches of the superior pancreatoduodenal and splenic arteries off the celiac axis
- And Inferior pancreatoduodenal artery off the SMA
- Lies immediately anterior to SMV-PV confluence and SMA
- Immediately inferior/anterior to splenic artery and vein
What do acinar cells produce?
- A multitude of digestive pro-enzymes that are secreted across the apical cell membrane into a tiny ductule at the center of each acinus
- Ductules coalesce into the larger exocrine duct system of the pancreas that ultimately leads to the main (ventral) duct and ampulla of Vater
- In about 10% of people the dominant route of flow is dorsal duct and empties into minor papilla
Over 80% of the pancreas is what cell type?
- 80% of pancreateic cells are epithelial in origin and comprise the acinar glands
- Form the exocrine component and are of import in this first unit
What are the proteases secreted by the pancreas?
- Trypsinogen
- Chymotrypsinogen
- Proelastase
- Procarboxypeptidase A
- Procarboxypeptidase B
What are the ‘other’ enzymes secreted by the pancreas?
- Amylase
- Deoxyribonuclease
- Ribonuclease
- Procolipase
- Trypsin inhibitors
- Monitor peptide
What are the lipases secreted by the pancreas?
- Lipase
- Lipase-related proteins
- Prophospholipase A1, A2
- Nonspecific esterase
Why are the bicarbonate and water secretions of the pancreas important?
- They help move all the enzymes down to where they need to (flow is important, stasis is bad)
- They also provide a high pH environment to discourage the activation of the zymogens
What is going on in acute pancreatitis?
- Occurs when pancreatic enzymes are inappropriately and prematurely activated resulting in autolysis of the gland
- May result in severe inflammation and/or necrosis of pancreatic tissue
- Most commonly occurs when pancreatic duct becomes obstructed, resulting in stagnation of pancreas enzymes within the organ and activation of enzyme activation cascade
Why might alcohol intake precipitate pancreatitis?
• Direct toxic effect on pancreatic acinar cells
• Premature release and activation of trypsinogen and stagnant flow of pancreatic juice
*alcohol abuse will often result in pancreatitis (if it does) within 3-5 days of the binge
Some people do have premature enzyme activation, but what keeps this from being a problem normally?
- Peristalsis of duct
- Sphincer of oddi relaxation
- Bicarbonate and water secretion and flow
- Trypsin inhibitor function
What congential ductal abnormalities would you find obstructing the pancreatic outflow and thus being associated with pancreatitis?
• Pancreas divisum
• Annular pancreas
○ Usually these just increase the risk of alcohol use precipitating the event
Hyperlipidemia is associated with what pancreatic disease?
• Severe hyperlipidemia may precipitate acute pancreatitis for numerous reasons which remain poorly understood
What are the less common, but still testable causes of acute pancreatitis?
• Drug induced ○ Thiazide diruetics ○ Azathioprine ○ Anti-retroviral drugs • Hypercalcemia • Infectious ○ Mumps ○ Coxsackievirus • Cystic fibrosis
What does the pancreas look like macroscopically and grossly in severe pancreatitis?
- Lipase released from dying acinar cells breaks down fat, liberating free fatty acids that precipitate with calcium ad form insoluble soaps
- Frank coagulation necrosis of the gland and/or hemorrhage into retroperitoneum
- Microscopically, necrosis of pancreatic tissue is associated with intense infiltrates of neutrophils and apoptosis of epithelial cells
What diagnostic tests are performed with clinical suspicion of pancreatitis?
• Blood test
○ Serum level of amylase and lipase
○ Elevated greater than 3 times the upper limit of normal
• Lipase more specific for pancreatitis and equally to slightly more sensitive than serum amylase
○ Rises 1-2 hours and decreases over following week
• Serum amylase rises and falls within 24-48 hours but its specificity is imperfect
○ Mumps, sjorgrens, penetrating peptic ulcer, intestinal trauma or ischemia, ectopic pregnancy
○ All these can confuse the findings
What imaging modalities can be used to help confirm the diagnosis of pancreatitis?
• Ultrasound and CT
• Ultrasound is cheaper and 90% accurate at detecting gallstones
○ BUT not great at looking at pancreas and ducts
• Contrast CT in severe cases or questionable situations
○ Shows inflammatory changes within and surrounding the pancreas-
§ gland edema, fat stranding, fluid accumulation
○ Can sometimes show the tumor cause
○ Certainly good for hemorrhage
What is ERCP?
Endoscopic retrograde cholangio-pancreatography (ERCP) is a diagnostic test to examine:
the duodenum (the first portion of the small intestine),
the papilla of Vater (a small nipple-like structure with openings leading to the bile ducts and the pancreatic duct),
the bile ducts, and
the gallbladder and the pancreatic duct.
How is acute pancreatitis treated?
• Hospital admission just in case things go south
• NPO status
• IV pain meds
• Time
○ Lame, yes, but majority of uncomplicated acute pancreatitis will improve with these supportive measures alone
• MUST avoid alcohol to prevent disease recurrence or progression to chronic pancreatitis
• Cholecystectomy later to remove source of obstruction
○ Otherwise healthy patients
• Stone removal by ERCP
• Can also be done surgically but that’s more messy
Describe (general) the disease state of chronic pancreatitis
• Condition that develops after repeated bouts of acute pancreatitis
• Commonly occurs as a result of chronic alcohol abuse
• Macrospic
○ Characterized by replacement of healthy pancreatic tissue by hard fibrous tissue
○ There may be atrophy of the gland as well
• Pancrease juice may become viscous, and calcifications/stones may devleop within duct if these clumps of protein precipitate with calcium salts
• Microscopic
○ Broad bands of scar tissue replace lost lobular tissue
○ Can show presence of lymphocytes and plasma cells
• There is usually sparing of islet cells
• Fibrous tissue can cause strictures of duct
• Calcified stones can precipitate obstruction
• Malabsorption, pain, malnutrition
What is the most common cause of CP in the west?
- CP = chronic pancreatitis
- Chronic alcohol abuse
- Cigarette smoking also contributed to fibrosis, and particularly in alcoholics
What are the inherited conditions that predispose people to chronic pancreatitis?
• CFTR mutations • Trypsinogen gene mutations ○ PRSS • Trypsin inhibitor mutations ○ SPINK • Familial hypertriglyceridemia • Equatorial countries - idiopathic variant that has extensive calcifications, called tropical pancreatitis
Why do pancreatic stellate cells have an important role in chronic pancreatitis?
- They, when stimulated, proliferate and transform into collagen-synthesizing cells
- Can contribute to the ductal obstruction
Fat malabsorption is a marker of what degree of pancreatic damage?
- 90% of the organ is destroyed before fat malabsorption is seen
- 95% for carbs and proteins because trypsin and amylase are produced elsewhere as well
What are the clinical manifestations of chronic pancreatitis?
- Steatorrhea is important finding
- Epigastic pain that radiates directly to back
- Can just present as back pain alone
- Pain will wax and wane but never truly disappear
What is steatorrhea
- Fatty diarrhea
- Frequent, oily, foul-smelling, and/or buoyant stools
- Increased flatulence and weight loss
What might patients with chronic pancreatitis have B12 deficiency?
- Pancreatic proteases are required to cleave the R-protien-cobalamin complex
- This allows for intrinsic factor to bond to B12
- Thus, pancreatic duct obstruction or atrophy will result in a loss of B12 binding to IF, and thus a malabsorption of B12
- Eventually causes macrocytic anemia
Why might bleeding diathesis develop in chronic pancreatitis?
• A result of fat-soluble vitamin malabsorption, specifically vitamin K
What diagnostic tests for chronic pancreatitis are available?
• History and physical can be highly suggestive
• Plain x-ray of abdomen can show calcifications scattered over epigastrium in severe calcific disease
• Rapid fat stool stain
○ Sudan stain, qualitiative
• Definitive is 72-hour quantitative stool collection for fat analysis
○ High fat diet of over 100g of fat/day
○ 72 hour stool collection should who over 10-20% fecal fat excretion or 50 g of fat
Pancreatic cancer is a major US killer. From what cells does this cancer arrive?
- Vast majority (90-95%) arise from ductal epithelial cells
- Remaining come from acinar cells
- Both carry a bad prognosis
- Cancer usually forms primitive, mucin-positive, gland-like structures
- Cells elicit a strong, fibrotic reaction known as desmoplasia, texture very hard and cancer cells less permeable to chemotherapy drugs
- Often have microscopic tumor tendrils that are not seen by imaging
What are the much more rare pancreatic tumors?
• Mucinous cystadenocarcinomas • Intraductal papillary mucinous tumors ○ IPMTs • Arise from cystic lesions in pancreas and much less common than ductal adenocarcinoma • More favorable prognosis
What are the risk factors for pancreatic adenocarcinoma?
• Positive family history • Tobacco abuse • Chronic pancreatitis • Obesity • Ocassionally a genetic syndorme ○ Peutz-Jeghers ○ Von Hippel-Lindau
