Pathology of the pancreas an gall bladder Flashcards
What are the different congenital anomalies of the pancreas?
1) Agenesis
2) Pancreatic divisum
3) Annular pancreas
4) Heterotopic pancreas
5) Cysts (true congenital, acquired “pseudocysts”, and neoplastic)
What is meant by pancreatic divisum?
when a single pancreatic duct is not formed, but rather remains as two distinct dorsal and ventral ducts
What is meant by annular pancreas?
- When part of the pancreas surrounds the second part of the duodenum in a ring form, which is continuous with the head of the pancreas
What is meant by heterotopic pancreas?
When pancreatic tissue is found outside the usual anatomical place of the pancreas
What is meant by pancreatitis?
- It is an inflammatory disorder of the pancreas, which ranges in severity from mild self-limited disease to a life-threatening disease
1) In the Acute pancreatitis the function of the pancreas can return back to normal if the underlying cause of inflammation is removed
2) In chronic pancreatitis, an irreversible destruction of the exocrine pancreatic parenchyma has occurred
What is acute pancreatitis?
- It is a group of reversible lesions that are characterized by inflammation of the pancreas, which ranges in severity from edema and fat necrosis to parenchymal necrosis (due to the activation of some enzymes) with severe hemorrhage
What are the causes of acute pancreatitis?
80% of cases are attributed to:
1) Biliary tract disease (gall stones)
2) Alcoholism (Ethanol “leads to the constriction of the sphincter of Oddi”)
- Other causes could include (MNEMONIC: I GET SMASHED):
3) Idiopathic
4) Trauma
5) Steroids
6) Mumps
7) Autoimmune
8) Scorpion venom
9) Hyperlipidemia/Calcemia/Hypothermia
10) Emboli
11) Drugs
What is the proposed pathogenesis of acute pancreatitis?
- It is caused by the injury of the acinar cells via 3 ways
1) Duct obstruction, which could be due to:
- Cholelithiasis
- Ampullary obstruction
- Chronic alcoholism
- Ductal concretions
- These will lead lead to
- Intestinal edema then impaired blood flow then ischemia which will ultimately cause the injury of the acinar cells (and thus the activation and release of the enzymes)
2) Defective intracellular transport, which could be caused by:
- Metabolic injury
- Alcoholism
- Duct obstruction
- These will lead to
- Defective delivery of the proenzymes to the lysosomal compartment and thus intracellular activation of the enzymes which will lead to the injury of the acinar cells
3) Acinar cell injury, which could be caused by:
- Alcohol
- Drugs
- Trauma
- Ischemia
- Viruses
- These will lead to:
- Release of intracellular proenzymes and lysosomal hydrolases, which will activate the intra and extracellular enzymes leading to the injury of the acinar cells
- The injury of the acinar cells will lead to the activation of the enzymes leading to:
1) Interstitial inflammation and edema
2) Proteolysis (via proteases)
3) Fat necrosis (via lipase and phospholipase)
4) Hemorrhage (via elastase)
These will collectively lead to acute pancreatitis
Describe the histological pathogenesis of acute pancreatitis
- Histological changes suggests autodigestion of the pancreatic substance by the inappropriately activated pancreatic enzymes
- Activation of trypsin is central in this process, and critical for triggering events in acute pancreatitis, trypsin can also activate itself as well as other proenzymes like phospholipases and elastases, which takes part in the process of autodigestion
- In addition to that trypsin also converts prekallikrein to its activated form, triggering the kinin system, and by the activation of factor 12 (hageman factor) which mobilizes the clotting and complement system
1) Fat necrosis due to the effect of the enzymes
2) Thinning of the blood vessels due to the effect of elastase
3) Red areas due to hemorrhage
4) Scattering of the inflammatory cells
What are the different investigations for acute pancreatitis?
1) Serum amylase and lipase (diagnostic)
- Serum lipase remain elevated longer than amylase and it more specific (due to the fact that amylase is present in the saliva also) but less sensitive
2) CRP (usually elevated)
3) Full blood count
4) Liver function test
5) Serum glucose
6) CT (might be required to show pancreatic edema, hemorrhage and necrosis)
7) Ultrasound scan (must be done within 48 hours of admission to identify gallstones in the bile duct
Describe the morphology of acute pancreatitis
- Ranges from trivial inflammation and edema to severe extensive necrosis and hemorrhage
- The basic alterations are (inflammation, necrosis, fatty tissue and hemorrhage):
1) Microvascular leakage causing edema (mainly due to elastase)
2) Necrosis of fat by the lipolytic enzymes
3) Acute inflammatory reaction
4) Proteolytic destruction of pancreatic parenchyma
5) Destruction of the blood vessels with subsequent interstitial hemorrhage (black reddish areas of hemorrhage)
Describe the gross features of acute pancreatitis
1) Peripancreatic fat
2) “Chalky” fat necrosis
3) Parenchymal necrosis
- So what we see many of the chalky areas , the whitish necrotic area compared to yellowish normal pancreatic parenchyma
What are the complications of acute pancreatitis?
- Early complications
1) Acute renal failure
2) DIC
3) Hypocalcemia
- Late complications
4) Formation of abscess/pseudoabscess
5) Fat necrosis
6) Hemorrhage
- Systemic complication
7) Shock
8) Organ failure
What is chronic pancreatitis?
- Characterized by the long-standing inflammation, fibrosis and the destruction of the exocrine pancreas
- The endocrine pancreas is also lost in the late stages
- The distinction between the chronic an acute pancreatitis is the irreversible impairment in the function of the pancreas
- FYI: Serum lipase and amylase tests are not diagnostic and the levels will be normal
What are the causes of chronic pancreatitis?
1) Long-term alcohol abuse (most common)
2) Long-standing pancreatic duct obstruction (due to pseudocysts, calculi, neoplasms, pancreas divisum, etc)
3) Tropical pancreatitis (seen in Africa and asia)
4) Hereditary pancreatitis (due to mutations in the pancreatic trypsinogen gene (PRRS1) OR (SPINK1) gene which encodes for trypsin inhibitor
Describe the gross structure of chronic pancreatitis
1) More whitish areas of fibrosis
2) Loss of the lobular surface
3) Shrinkage in size due to the extensive fibrosis and destruction
Describe the microscopic photo of chronic pancreatitis
1) Extensive fibrosis
2) Inflammation
3) Destruction of the ducts
4) Pseudocysts (ducts that appears dilated and enlarged “they look like a real cyst but they are not”)
Where does pancreatic cancer occur in the pancreas?
1) 60% in the head
2) 20% Diffusely involves the entire gland
3) 15% In the body of the pancreas
4) 5% In the tail of the pancreas
- Most carcinomas are ductal adenocarcinomas
- It is one of the causes of obstructive jaundice
- Usually when discovered the patient has less than 1 year (due to it being highly invasive)
What are the characteristic features of pancreatic cancer?
1) Highly invasive
2) They elicit an intense non-neoplastic host reaction composed of fibroblasts, lymphocytes and the extracellular matrix (desmoplastic response), desmoplasia occurs due to the increased synthesis of the extracellular matric proteins and collagen by the stromal cells
What are the risk factors for pancreatic cancer?
- It ha no known cause but it is seen more in developing countries
1) Cigarette smoking
2) Obesity
3) Diabetes type 2
4) Chronic pancreatitis
5) Liver cirrhosis
6) Other infections like H.Pylori
7) Environmental toxins
Describe the gross morphology of ductal adenocarcinoma
Very white, dense, strong, firm in structure due to the extensive fibrosis which invades the adjacent structures
Describe the histopathology of ductal adenocarcinoma
1) It arises from the ductal (glandular) epithelium)
2) It is moderately to poorly differentiated adenocarcinoma
3) Commonly there is perineural & angiolymphatic invasion
4) There is a marked desmoplastic reaction (pinkish area which represents extensive fibrosis)
- It is almost always associated with chronic pancreatitis
Describe the structure of the gallbladder
- The gallbladder is a pear-shaped organ consisting of four parts (fundus, body, neck and infundibulum)
What are the anomalies of the extrahepatic bile ducts and the gallbladder?
1) Congenitally absent gallbladder
2) Duct duplication
3) Bilobed gallbladder
4) Phrygian cap
5) Hypoplasia/Agenesis
What is cholelithiasis?
Gallstones
- Due to the accumulation of concentrated substances
What are the different types of gallstones?
1) Cholesterol stones
2) Pigment stones
3) Mixed stones
4) Stones with calcium content
What are the different causes of the yellow/green cholelithiasis?
- These are radiolucent cholesterol stones due to the increased cholesterol in bile, exceeding the capacity of the bile acids and lecithin to keep it soluble which could be due to (Hype saturation of cholesterol):
1) Imbalance between the bile composition
2) Increased production of cholesterol
3) Problem in emptying the bile
What are the risk factors for the cholesterol stones?
- Old age
- Females (estrogen increases HDL)
- Sudden weight reduction
- Hyperlipidemia
- Clofibrate (an antilipidemic agents)
- Crohn’s
- Cirrhosis (due to the decreases production of the bile salts)
What is the cause of a pigment stone (bilirubin salts)?
- Radio-opaque “it can be seen” (bilirubin + calcium) Brown/Dark in color
- Could be due to:
1) A lot of bilirubin
2) Chronic extravascular hemolysis
3) Biliary infection
What are the symptoms of gallstones (cholelithiasis)?
1) Fever (due to the inflammation of the gallbladder)
2) Jaundice
3) Abdominal pain (which radiates to the back)
4) Nausea and vomiting (after eating fatty food)
What are the complications of gallstones?
1) In the gallbladder
- Acute cholecystitis
- Chronic cholecystitis
- Empyema of the gallbladder
- Mucocele gallbladder
- Perforation (leading to biliary peritonitis)
- Gangrene of the gall bladder
- Carcinoma
2) In the bile duct
- Obstructive jaundice
- Cholangitis
- Acute pancreatitis
3) In the intestine
- Acute intestinal obstruction
What is cholecystitis?
Inflammation of the gallbladder
- Hand in hand with stones of the gallbladder/ducts
- Id surgery is required as a treatment, then mainly it is laparoscopic
What are the types of cholecystitis?
1) Acute
2) Chronic
What are the symptoms of acute cholecystitis?
- Fever
- Leukocytosis
- RUQ pain
What are the symptoms of chronic cholecystitis?
Subclinical (discovered accidentally) or pain
How to diagnose cholecystitis?
1) Hepatobiliary iminodiacetic acids (HIDA)
- Used to diagnose problems of the liver, gallbladder and the bile duct
2) Ultrasound
What are the presentations of acute cholecystitis?
1) RUQ pain which radiates to the right scapula
2) Pressure behind the gallbladder, which squeezes the blood vessels in the wall, which might lead to ischemia, bacterial overgrowth, and inflammation
3) Fever
4) Increased WCC
5) Nausea and vomiting
6) Increased alkaline phosphate in the epithelium of the gallbladder and the biliary tree
- If untreated then rupture is a risk factor
