Pancreatic Disorders Lecture 11 PDF

Pancreatic Disorders  1. The Pancreas Location Complex organ (endocrine and exocrine) Exocrine tissue Acinar cells (cluster around tubes) Wikimedia Commons, 2024 Essential for digestion Delivery of products into the small intestine Digestive enzyme...

Pancreatic Disorders  1. The Pancreas Location Complex organ (endocrine and exocrine) Exocrine tissue Acinar cells (cluster around tubes) Wikimedia Commons, 2024 Essential for digestion Delivery of products into the small intestine Digestive enzymes (juice) Amylase, lipase, nucleases, proteolytic enzymes (vesicles) Trypsin, chymotrypsin and carboxypeptidase (zymogen or proenzyme) Bicarbonate (ductal cells) Axelsson et al 2010 Pancreatitis 2. Pancreatitis Inflammation of the pancreas Destruction by enzymes Zymogens activated in pancreas Acute and chronic pancreatitis Causes of acute and chronic pancreatitis Gallstones Heavy alcohol consumption Less commonly: trauma, infections, unknown Wikimedia Commons, 2024 2.1 Acute Pancreatitis Sudden inflammation It can be life-threatening It can cause hemorrhage Causes Gallstones and alcohol use Trauma Medications Infections Wikimedia Commons, 2024 Tumours Symptoms: pain, fever, nausea, and vomiting Around 80% of cases resolve on their own or treatment It can lead to chronic pancreatitis ❖ Digestive Enzymes - Amylase Converts starch into sugar Also produced by salivary glands (isoenzymes) Routinely measured (marker) Alerts for acute pancreatitis Levels of amylase in serum 2 to 12 hours after onset of acute pancreatitis (8X RI) Normal levels 3 to 4 days after onset of symptoms Less specific than serum lipase Reference interval: 30-110 IU/L (LifeLabs) ❖ Digestive Enzymes - Lipase Breaks down triglycerides Levels of lipase in serum 4 to 8 hours after onset of acute pancreatitis (2 to 50X RI) Normal levels 8 to 14 days after onset of symptoms More specific and sensitive than serum amylase RI: < 60 U/L (LifeLabs) 2.1 Acute Pancreatitis - Diagnosis Most important markers Serum amylase assay Serum lipase assay Trypsinogen activation peptide (TAP) Released during activation of trypsinogen Blood and urine Early diagnosis Determination of severity May be associated with severe form of acute pancreatitis Other tests Phospholipase A2 (inflammation) Procalcitonin (e.g., infection) C-reactive protein (CRP) Knowledge on progression of inflammation 2.2 Chronic Pancreatitis Destruction of pancreas by digestive enzymes Inflammation progresses over time Permanent damage “Digestion” of the pancreas Severe pain/loss of function Scar tissue and calcium Slow destruction of the pancreas Diabetes Pancreatic insufficiency Cause Heavy alcohol consumption In children: cystic fibrosis 2.2 Chronic Pancreatitis - Diagnosis Challenging diagnosis Blood tests are not good to detect early disease Pancreas has large functional reserve Common pancreatic enzymes measured: Trypsin, amylase, lipase, chymotrypsin, and elastase Consequences: diabetes and pancreatic insufficiency Pancreatic insufficiency detected when 50% acinar cells destroyed Test interpretation: Medical history (persistent enzyme elevation/flare-ups) Other clinical and imaging findings Maldigestion and Malabsorption 3. Maldigestion and Malabsorption Decrease the ability of body to absorb nutrients Malabsorption Abnormalities in distal part of digestive tract Food not properly absorbed Maldigestion Abnormalities in proximal part of digestive tract (pancreas) Wikimedia Commons, 2024 Reduction or lack of digestive enzymes and bicarbonate Food not broken down properly Symptoms/Signs of maldigestion and malabsorption Weight loss, fatigue, abdominal discomfort, flatulence, steatorrhea, etc. Causes: Chronic pancreatitis, medications, tumours, celiac disease, etc. 4. Pancreatic Insufficiency Deficiency of digestive enzymes Maldigestion and malabsorption Early malabsorption condition Mild gastrointestinal symptoms Fatigue and anorexia Laboratory significance: Early laboratory tests Antibody tests for celiac disease Hemoglobin, MCV, folate, ferritin, calcium Albumin Later in the disease course: additional laboratory tests Fecal fat, fecal pancreatic elastase 1, secretin-cholecystokinin, trypsin, and trypsinogen tests 4.1 Additional Diagnostic Tests ❖Fecal Fat Test Non-specific Fat in the stool Indicates malabsorption or maldigestion Qualitative test Sudan stain IV Quantitative test 72-hour fecal test High-fat diet for 4 days Utilize pre-weighted collection container Nuclear magnetic resonance spectroscopy (RI: Less than 7g fat in 24 Hrs) Elevated level of fecal fat indicates malabsorption disorder 4.2 Additional Diagnostic Tests ❖Fecal pancreatic elastase 1 test Good indicator of exocrine pancreatic insufficiency Sensitive and specific Non-invasive ELISA Low levels Indicative of pancreatic insufficiency Less expensive than the “gold standard” secretin-cholecystokinin 4.3 Additional Diagnostic Tests ❖Secretin-cholecystokinin test “Gold standard” Used to help diagnosing pancreatic malfunction Combination of the secretin test and cholecystokinin test Assesses the function of the pancreas and gallbladder Secretin (duodenum) Acidic chyme - bicarbonate-rich pancreatic juice is stimulated Cholecystokinin (duodenum and jejunum) Stimulates amylase, trypsin and lipase release and bile (gallbladder) 4.4 Additional Diagnostic Tests ❖Trypsin Stool test Trypsin function Indicates pancreatic function 4.5 Additional Diagnostic Tests ❖Trypsinogen (blood) Released by the pancreas Trypsinogen is converted into trypsin Blood measurements Lower than normal levels in blood Indicator of pancreatic insufficiency Wikimedia Commons, 2024