Acute and Chronic Pancreatitis By Dr. Zahoor

Objectives We will study 1. Pancreas – normal structure and function 2. Acute Pancreatitis – pathogenesis, presentation, investigation and treatment 3. Chronic Pancreatitis – pathogenesis,

Pancreas Structure and Function Pancreas lies retroperitoneally across the posterior abdominal wall from the second part of duodenum to the spleen Pancreatic head is encircled by the duodenum and tail is in contact with spleen Pancreas has exocrine cells – 98% and endocrine cells – 2%

Pancreas Anatomy – Structure and Functions

Pancreas The main pancreatic duct joins the common bile duct to enter the duodenum as a single duct at the ampulla of valter What is the importance? Gall stones or cholecystitis can cause pancreatitis

Clinical presentation of Gallstones

Pancreas Exocrine Function of Pancreas The pancreas Acinar cells produce digestive enzymes – amylase, lipase, colipase and proteases – Trypsinogen and Chymotrypsinogen

Pancreas Endocrine Function of Pancreas Hormone producing cells are islets of langerhans secrete hormone There are five types of islets cells 1. Beta cells secrete insulin 2. Alpha cells secrete glucogan 3. D – Cells secrete Somatostatin 4. PP cells produce pancreatic polypeptide 5. Entrochromaffin cells produce serotonin

Pancreatitis Pancreatitis is divided into 1. Acute Pancreatitis 2. Chronic Pancreatitis We will discuss each one

Acute Pancreatitis It is acute inflammation of Causes of Acute Pancreatitis Acute Pancreatitis It is acute inflammation of pancreas, which occurs in previously normal pancreas and returns to normal after resolution.

Pathogenesis of Acute Pancreatitis It is due to activation of digestive enzyme Trypsinogen to Trypsin within pancreas, may be caused by rise in intracellular Ca2+ which may trigger it May be due to impairment of Trypsin degradation Activated enzyme Trypsin causes cellular nacrosis

Pathogenesis of Acute Pancreatitis Gall stones cause pancreatitis by blocking pancreatic drainage at the level of ampulla Alcohol – interferes with Ca2+ homeostasis in pancreatic Acinar cells

Clinical Features of Acute Pancreatitis Pain in epigastric region accompanied by nausea and vomiting. Pain radiates to the back. Inflammation spreads throughout the peritoneal cavity. Involvement of retro peritoneum leads to back pain.

Clinical Features of Acute Pancreatitis Patient may give history of gall stones or alcohol intake In severe cases, there may be hypotension, tachycardia, and oligurea

Clinical Features of Acute Pancreatitis Abdominal examination - May show tenderness and guarding and reduced or absent bowel sounds Specific clinical signs in severe necrotizing Pancreatitis Cullen signs – periumblical bruising Greyturner’s sign – flank bruising

Greyturner’s sign

Diagnosis of Acute Pancreatitis Blood test Serum amylase – increased three times more than normal within 24 hours of onset of pain Amylase falls back to normal in 3-5 days Serum Lipase – increased Urine amylase Do other base line investigations - Blood count, urea and electrolyte, blood glucose, liver biochemistry, plasma calcium, arterial blood gases - They help in assessing the severity of the attack

Diagnosis of Acute Pancreatitis Radiology Erect X-ray abdomen – to exclude gastroduodenal perforation Supine abdominal film – may show gall stones or pancreatic calcification Abdominal Ultrasound - To look for gall stones in common bile duct, dilated intrahepatic duct, also for pancreatic swelling, nacrosis, and peripancreatic fluid collection

Radiology (cont) Contrast enhanced CT scan Should be performed after 72 hours to see for pancreatic necrosis CT can detect fluid collection, abcess formation and pseudocyst development MRI and MRCP (Magnetic Resonance cholangiopancreatography) for pancreatic duct and Biliary tree Endoscopic retrograde cholangiopancreatography (ERCP) – used as treatment to remove the duct stones in gall stone related pancreatitis

Pancreatitis Assessment of Disease Severity

ACUTE PANCREATITIS – GLASGOW CRITERIA P - PaO2 < 8kPa A - Age > 55 years N - Neutrophalia WBC > 15 × 109 /l C - Calcium < 2 mmol/l R - Renal function urea > 16 mmol/l E - Enzyme LDH > 600 iu/l, AST > 200 iu/l A - Albumin < 32g/l S - Sugar blood glucose > 10 mmol/l If patient score 3 or more, it indicates severe pancreatitis and patient should be transferred to ITU

Pancreatitis Assessment of Disease Severity Majority of cases of pancreatitis are mild and run short self limiting course But about 25% cases run complicated course and 10% may be life threatening Increased CRP > 200mg/L in first four days signifies severity

Abdominal CT showing swollen pancreas

CT Abdomen showing pancreatic pseudocyst (Ps cyst)

Treatment IV fluids Nasogastric suction – prevents abdominal distension and vomitus and decreases risk of pneumonia Blood gases – will guide for O2 administration Antibiotic – Cefuroxime (reduces incidence of pancreatic nacrosis) Analgesia – Pethidine or Tramadol (Avoid morphine as it causes contraction of sphincter of ODDI)

Long term outcome Mild and moderate cases of pancreatitis usually make full recovery Severe acute pancreatitis may cause pancreatic insufficiency. Both exocrine (malabsorption) and endocrine (diabetes).

CHRONIC PANCREATITIS

Causes of Chronic Pancreatitis In developed countries, cause of chronic pancreatitis is alcohol in 60-80% cases. Other causes can be metabolic, genetic, autoimmune

Chronic Pancreatitis Pathogenesis Increased activated trypsin or impaired clearance of trypsin Increased trypsin leads to precipitation of protein within the pancreatic duct lumen in the form of plugs and causes duct obstruction Increase alcohol causes chronic pancreatitis by impairing Ca2+ regulation which promotes Trypsinogen activation to trypsin

Chronic Pancreatitis Genetic aspect of chronic pancreatitis Genetic factors may be responsible for trypsin activations e.g. cystic fibrosis CFTR (cystic fibrosis transmembrane conductance regulator) in apical surface of Acinar cells Auto immune chronic pancreatitis (ACP) There is increased IgG4 level, this process is not dependent on trypsin

Chronic Pancreatitis Clinical features Pain – epigastric region, radiates to the back Anorexia and weight loss Exocrine and endocrine insufficiency may develop i.e. malabsorption or diabetes may be presenting feature

Investigation Serum amylase and lipase may be increased Faecal elastase – abnormal (decreased) in majority of cases of chronic pancreatitis Transabdominal ultrasound scan Contrast enhanced spiral CT-scan - provides more assessment for calcification in dilated pancreatic duct

Contrast CT showing multiple calcification in pancreas

Investigation MRI and MRCP (magnetic resonance cholangiopancreatography) Endoscopic ultrasounds – for assessing complication including pseudocyst formation Diagnostic ERCP (endoscopic retrograde cholangiopancreatography) – it has been replaced by MRCP

Treatment of Chronic Pancreatitis Chronic pancreatitis if alcohol related then long term abstinence is advised For abdominal pain - Opiate – Tramadol - NASAID (Non steroidal anti-inflammatory drugs) - For chronic pain, amitryptyline (tricyclic antidepressants) - Stent of pancreatic duct to maintain duct patency

Treatment of Chronic Pancreatitis For Steatorrhea - Pancreatic enzymes - H2 – receptor antagonist or proton pump inhibitors – to neutralize acidity in duodenum Diabetes due to pancreatic disease may need insulin

Complications of Chronic Pancreatitis Pancreatic pseudocyst – (fluid collection surrounded by granulation tissue) If pseudocyst is < 6cm in diameter, spontaneous resolution may occur Pseudocyst can be drained endoscopically, using endoscopic ultrasound

Complications of Chronic Pancreatitis Other complication of chronic pancreatitis - Ascites - Pleural effusion (rare) – increased amylase in pleural fluid will confirm the etiology - Increased risk of cancer in chronic pancreatitis

Additional Information Clinical Syndromes - pancreas Insulinoma Gastrinoma VIPoma Glucagonomas Somatostatinomas

Insulinomas Insulinomas are pancreatic cell tumor, derived from beta cells that secret insulin Classic presentation is fasting hypoglycemia Other presenting feature may be sweating, palpitation, weakness Diagnosis is confirmed by demonstration of hypoglycemia with normal or elevated insulin level

Gastrinoma There is hyper secretion of gastric acid secondary to ectopic gastrin secretion within endocrine pancreas – Zollinger - Ellison Syndrome Patient has recurrent severe duodenal ulceration Diagnosis is confirmed by elevated gastrin level High dose proton pump inhibitors are used to suppress the symptoms

VIPoma Endocrine pancreatic tumor producing VIP (Vasoactive Intestinal Polypeptide) This causes severe secretary diarrhea due to stimulation of Adenyl cyclase – Verner - Morrison Syndrome (clinical syndrome causing profuse watery diarrhea, hypokalemia and metabolic acidosis)

Glucagonomas Glucagonomas are α-cell tumors responsible for migratory necroletic dermatitis, weight loss, diabetes mellitus, deep vein thrombosis, anemia and hypoalbumiaemia Diagnosis is made by measuring pancreatic glucogan in the serum

Somatostatinomas Somatostatinomas are rare malignant D cell tumors of the pancreas They cause diabetes mellitus, gall stones, diarrhea, Steatorrhea They can be diagnosed by high serum somatostatin level

THANK YOU