Objectives: At the end of the two lectures the students will be able to: 1. Recognize the predisposing factors of pancreatitis. 2. Describe the different types of pancreatitis. 3. Understand the pathogenesis of acute and chronic pancreatitis..
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1 Mind maps:
2 Introduction:
Anatomy of the pancreas: The pancreas is a transversely oriented retroperitoneal organ extending from the C loop of the duodenum to the hilum of the spleen.1 The pancreas is in reality two organs in one: 1. 90% exocrine (involved in digestion by secretion of digestive enzymes). - Its dysfunction usually results in problems with digestion & absorption, and the released hydrolytic enzymes will cause tissue destruction (usually exocrine is damaged first). 2. 10% endocrine (secretes hormones e.g. insulin ) - Its dysfunction will cause diabetes.
Pancreatitis: Definition: Pancreatitis encompasses a group of disorders characterized by inflammation of the pancreas. Clinical manifestations: can range in severity from a mild, self-limited disease2 to a severe and life threatening acute inflammatory process. Duration: range from a transient attack to an irreversible loss of function. Types: 1. Acute pancreatitis: gland can return to normal if underlying cause of the pancreatitis is removed. 2. By contrast, Chronic pancreatitis: is defined by irreversible destruction of exocrine pancreatic parenchyma “the endocrine part may involved later”.
NOTE: both entities ”acute and chronic” share similar pathogenic mechanisms, and indeed recurrent acute pancreatitis can result in chronic pancreatitis (in a chronic pancreatitis an acute attack can occur).
1 The retroperitoneal location of the pancreas and the generally vague nature of signs and symptoms associated with its injury or dysfunction allow many pancreatic diseases to progress undiagnosed for extended periods of time. 2 The patient may does not even know that he had an onset. 3 Acute pancreatitis Acute pancreatitis: is a group of reversible lesions characterized by inflammation of the pancreas ranging in severity from focal edema and fat necrosis to parenchymal necrosis with severe hemorrhage.
Etiology: Common factors Less common
Obstruction of the pancreatic duct system3: ➢ 80% of cases in Western countries are - eg. periampullary tumors, congenital cystic associated with one of two conditions: dilatation of the common bile duct, alcoholism, biliary tract disease. biliary"sludge"4, and parasites (particularly 5 6 ➢ Gallstones are present in 35% to 60% of cases Ascarasis lumbricoides and Clonorchis sinensis of acute pancreatitis. organisms). - Roughly 5% of patients with gallstones Medications: More than 85 drugs have been develop acute pancreatitis, and gallstones reported to cause acute pancreatitis. These include are implicated in 35% to 60% of cases thiazide diuretics, azathioprine(immunosuppressant), overall. estrogens, etc.
Metabolic disorders: including hypertriglyceridemia, hyperparathyroidism, and other hypercalcemic states. Ca “enzyme activator” → will cause premature activation of trypsin → activation of other pancreatic enzyme” → pancreatitis.
Infectious: - Mumps. - Coxsackievirus. - Mycoplasma pneumoniae. Acute ischemia: induced by vascular thrombosis, embolism, vasculitis (polyarteritis nodosa) and shock.
Trauma: both blunt trauma and iatrogenic injury (caused by a doctor) during surgery or endoscopic retrograde cholangiopancreatography7.
Genetic: such as mutations in SPINK1 and PRSS1.
3 Non-gallstones related obstructions. 4 A mixture of particulate solids that derived from bile.Ex:cholesterol crystals,calcium salts). 5 Associated with poor personal hygiene, poor sanitation, and in places where human feces are used as fertilizer. 6 People become infected when eating the parasite containing cysts within infected raw or undercooked fish. 7 Specialized technique used to study the bile ducts, pancreatic duct and gallbladder. 4 Morphology: It ranges from: Inflammation and edema ⇒ severe extensive necrosis and hemorrhage. The basic alterations are: Mnemonic: MIND - M= Microvascular leakage → edema. - I= Acute Inflammatory reaction. - N= lipolytic enzymes → fat necrosis - D=Protease → Destruction of pancreatic parenchyma. - Elastase → hemorrhage. Fat necrosis, results from enzymatic destruction of fat cells; The released fatty acids⇒ combine with calcium⇒ form insoluble salts that precipitate in situ (in same place it was formed). *Dystrophic calcification (calcification occurring in degenerated or necrotic tissue). Pathogenesis: 8 Autodigestion of the pancreatic substance by inappropriately activated pancreatic enzymes . Thus, activation of trypsinogen9 is an important triggering event in acute pancreatitis. If trypsin is inappropriately generated from its proenzyme trypsinogen, it can activate itself as well as other pro enzymes (e.g., phospholipases and elastases) that can then take part in the process of autodigestion. The pathways that can lead to the enzyme activation are:
8 The pancreas is normally protected from autodigestion by synthesis of pancreatic enzymes in the acinar cells in the proenzyme form. 9 Precursor form of trypsin. (meaning preactivation of trypsin) 5 Clinical Features: (Dr Al Humaidi said all of these are not important just focus on the first point). ⭑ Abdominal pain10 is the cardinal manifestation of acute pancreatitis. Its severity varies from mild to severe. - Characteristically, the pain is constant and intense and is often referred to the upper back. • Leukocytosis, hemolysis. • Diffuse fat necrosis. • Full-blown acute pancreatitis is a medical emergency of the first magnitude. These patients usually have the sudden onset of an "acute abdomen" that must be differentiated from diseases such as: - Ruptured acute appendicitis. - Perforated peptic ulcer. - Acute cholecystitis11 with rupture. - Occlusion of mesenteric vessels with infarction of the bowel.
Laboratory findings: (very important) marked elevation of serum amylase levels during the first 24 hours, followed within 72 to 96 hours by a rising serum lipase level. Lipase is more specific, but needs more time to be elevated. Management:
• The key to the management is "resting the pancreas” by total restriction of food and fluids and by supportive therapy. • Most patients recover fully. About 5% die from shock during the first week of illness.
Complications: (patient might be present by them directly as clinical manifestation). • Pancreatic pseudocyst. • Sterile Pancreatic abscess (neutrophil aggregation sterile not from infections). • Shock: due to fluid sequestration12. • Peripheral vascular collapse. • Acute renal tubular necrosis. • Disseminated intravascular coagulation “DIS” (Fatal)13. • Acute respiratory distress syndrome14 “ARDS” (Fatal).
10 Radiates to the back. 11 inflammation of the gallbladder. 12 ﺣﺒﺲ 13 Widespread activation of the clotting cascade that results in the formation of blood clots in the small blood vessels throughout the body. 14 Because of the free destructive enzymes 6 Chronic pancreatitis
• Chronic pancreatitis is characterized by long standing inflammation of the pancreas with destruction of exocrine parenchyma, fibrosis, and, in the late stages the destruction of endocrine parenchyma15. • The chief distinction between acute and chronic pancreatitis is the irreversible impairment in pancreatic function that is characteristic of chronic pancreatitis. Causes:
• There is significant overlap in the causes of acute and chronic pancreatitis.
Common causes Less common
- Long term alcohol abuse. - Hypercalcemia, hyperlipidemia. - Long term biliary tract disease. - Long-standing obstruction of the pancreatic duct by pseudocysts, calculi, trauma, neoplasms, or These patients are usually middle-aged males. pancreas divisum16. - Tropical pancreatitis, which is a poorly characterized disease seen in Africa and Asia. It has been attributed to malnutrition. - Hereditary pancreatitis (PRSS1 mutation ) - Idiopathic chronic pancreatitis. - Recurrent bouts of acute pancreatitis may also be a cause.
15 Will lead to diabetes mellitus. 16 Congenital anomaly in the anatomy of the ducts of the pancreas in which a single pancreatic duct is not formed, 7 Morphology:
Characterized by: • Parenchymal fibrosis. • Reduced number and size of acini (acinar atrophy) with relative sparing of the islets of Langerhans. • Variable dilation of the pancreatic ducts. These changes are usually accompanied by a chronic inflammatory infiltrate around lobules and ducts.
Grossly: gland is hard (because of extensive fibrosis), sometimes with extremely dilated ducts and visible calcification.
. Clinical Features: • Silent or recurrent attacks of abdominal pain, or persistent abdominal and back pain. • Attacks may be precipitated by alcohol abuse, overeating (which increases demand on the pancreas), or the use of opiates and other drugs. • During an attack of abdominal pain, there may be mild fever and mild-to-moderate elevations of serum amylase. • Calcifications can be seen within the pancreas by abdominal x ray.
Complications: 1. Severe pancreatic exocrine insufficiency and chronic malabsorption17 . .(diabetes mellitus (due to destruction of islets of Langerhans،e ndocrine part .2 3. severe chronic pain and pancreatic pseudocysts.
17 May cause weight loss. 8 PSEUDOCYSTS OF PANCREAS • A common sequela18of acute pancreatitis (usually present after 4-6 weeks of pancreatitis). • Pseudocysts are localized collections of necrotic-hemorrhagic material rich in pancreatic enzymes19 such cysts lack an epithelial lining (hence the prefix "pseudo") instead it’s lined by a fibrotic wall formed by the inflammatory process20, and they account for majority of cysts in the pancreas (75%). • Pseudocysts usually arise after an episode of acute pancreatitis, or of chronic pancreatitis. • Traumatic injury to the abdomen can also give rise to pseudocysts. • Amylase and lipase are usually elevated but not high as acute pancreatitis.
Complications:
• While many pseudocysts spontaneously resolve, they may become secondarily infected. • Larger pseudocysts may compress and perforate into adjacent structures. • They can produce abdominal pain and predispose to intraperitoneal hemorrhage or peritonitis.
Cyst: lined by epithelial tissue. pseudocyst: without epithelial lining.
Morphology: • Solitary. • Range in size from 2 to 30 cm in diameter. • Pseudocysts form by walling of areas of hemorrhagic fat necrosis.
Gross Microscopic
Cross-section through this previously bisected Histologically, the cyst lacks a true epithelial lining lesion revealing a poorly defined cyst with a and instead is lined by fibrin and granulation necrotic brown-black wall. tissue,with typical change of chronic inflammation.
18Condition that is the consequence of a previous disease or injury. 19 Due to disruptions of the pancreatic duct 20 Inflammation is mainly caused by autodigestion of pancreas caused by the leaking enzymes 9 Summary:
Acute Pancreatitis Chronic Pancreatitis
Type of lesion Reversible. Irreversible.
Etiology Gallstone, alcohol, others. Gallstone. alcohol, others.
- Activation of trypsinogen. Pathogenesis Activation of trypsinogen. - Fibrotic destruction.
- Fat necrosis. - Fibrosis. Morphology - Hemorrhage. - Acinar atrophy.
Acute abdominal pain that radiates to the Clinical features Chronic abdominal pain. back.
Investigations Elevated serum amylase. Mild serum amylase.
- Irreversible impairment in - Shock. pancreatic function. - Pancreatic abscess. Complications - Chronic malabsorption. - Acute respiratory distress syndrome. - Diabetes mellitus. - Pancreatic pseudocyst. - Pancreatic pseudocyst.
10 MCQ’s:
1- A 52 year old male present to the accident and emergency complaining of a severe abdominal pain radiating to the back. The patient is known alcoholic . He is found to have increased serum amylase. What is the most likely diagnosis in this case? A. Chronic pancreatitis. B. Acute pancreatitis. C. Perforated colon. D. Acute appendicitis.
Answer: B.
2- A 67 year old male is operated for removal of a pancreatic lesion. The patient history includes an episode of acute pancreatitis 2 years ago. The most likely histological feature on microscopic examination is the presence of a: A. Serous cyst. B. Mucinous cyst. C. Pancreatic pseudocyst. D. Choledocal cyst.
Answer: C.
3- Fibrosis, cystic dilatation of the ducts, loss of the pancreatic acini and lymphocytic infiltration of the pancreas are most likely seen in: A. Chronic pancreatitis. B. Infiltrating ductal carcinoma of the pancreas. C. Acute pancreatitis. D. Solid pseudopapillary tumor of the pancreas.
Answer: A.
4- Patients with acute pancreatitis may develop : A. Loss of the islets of Langerhans and the onset of diabetes. B. Acinar cell carcinoma secondary to the inflammation. C. Cushing syndrome with hypercortisolemia. D. Solid pseudopapillary tumor of the pancreas.
Answer: A.
5- The most frequent cause of acute pancreatitis is : A. Ascariasis lumbricoides. B. Periampullary tumor. C. Gallbladder stones. D. Medications.
Answer: C.
11 6- What are the most frequent laboratory findings in patients with acute pancreatitis? A. Elevation of serum lipase followed by elevation of amylase. B. Normal amylase level with elevation of lipase level only. C. Normal lipase level with elevation of amylase level only. D. Elevation of amylase levels followed by a rising of lipase. Answer: D. 7- A 60-year-old alcoholic man presents with a 6-month history of recurrent epigastric pain, progressive weight loss, and foul smelling diarrhea. The abdominal pain is now almost constant and intractable. An X-ray film of the abdomen reveals multiple areas of calcification in the mid-abdomen. Which of the following is the most likely diagnosis? A. Carcinoid syndrome. B. Chronic pancreatitis. C. Crohn disease. D. Insulinoma. E. Miliary tuberculosis. Answer: B.
8- Which of the following findings is most likely to be encountered in the patient described in previous Question ? A. Achlorhydria. B. Hypoglycemia. C. Melena. D. Pernicious anemia. E. Steatorrhea. Answer: E. Explanation: Steatorrhea due to fat malabsorption, B is incorrect because loss of pancreatic islet cells would be associated with hyperglycemia.
9- A 50-year-old woman complains of persistent abdominal pain, anorexia, and abdominal distention. Her past medical history is significant for a previous hospitalization for acute pancreatitis. A CT scan of the abdomen shows a fluid-filled cavity in the head of the pancreas. What is the most likely diagnosis? A. Acute hemorrhagic pancreatitis. B. Insulinoma. C. Pancreatic cystadenoma. D. Pancreatic islet cell tumor. E. Pancreatic pseudocyst.
Answer: E.
12 SAQ’s:
1. How is chronic pancreatitis different from acute pancreatitis? Chronic pancreatitis is defined by irreversible destruction of exocrine pancreatic parenchyma while acute pancreatitis is a reversible condition.
2. In a case of acute pancreatitis, what are the main histopathological findings expected to be found? Microvascular leakage causing edema, fat necrosis, parenchymal necrosis, and severe interstitial hemorrhage.
3. The two most common causes of acute pancreatitis are? Biliary tract disease and alcoholism.
4. Mention some drugs that were found to cause acute pancreatitis? Azathioprine, estrogens, and thiazide diuretics.
5. Describe briefly the pathogenesis of acute pancreatitis? A process of autodigestion of the pancreatic substance is activated by pancreatic enzymes. Activation of trypsinogen is an important triggering event in this process.
6. Mention some differential diagnosis of acute pancreatitis? Ruptured acute appendicitis, perforated peptic ulcer, and acute cholecystitis.
7. What is the most specific serum marker for acute pancreatitis? Elevated levels of pancreatic lipase.
8. What are you expected to see in the gross morphology of chronic pancreatitis? The gland is hard, sometimes with extremely dilated ducts and visible calcification.
9. One of the most serious complications of chronic pancreatitis is? Diabetes mellitus due to destruction of islets of Langerhans.
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