Pancreatic Disorders PDF

CHAPTER 28 PP 590-597, 599 Functions of GI Tract Digestion Absorption Synthesis of paracrine hormones Controlling gut motility Release of digestive enzymes  CHO digestion and absorption Polysaccharides Starch Salivary and pancreatic -...

CHAPTER 28 PP 590-597, 599 Functions of GI Tract Digestion Absorption Synthesis of paracrine hormones Controlling gut motility Release of digestive enzymes  CHO digestion and absorption Polysaccharides Starch Salivary and pancreatic - Amylose amylases Amylopectin Disaccharides Maltose Maltase (-glucosidases) Sucrose Sucrase Lactose Lactase (-galactosidase) Monosaccharides Glucose, Fructose, Galactose,…etc Digestion and absorption of polysaccharides depends on normal pancreatic function CHO digestion G G G G G G G G + G G amylose maltotriose maltose amylose G G G G G G G G G G G G G G G G G amylopectin amylopectin -limit dextrins Disaccaridases & oligosaccharidases Brush border enzymes Associated with intestinal mucosal cells (luminal side) Sucrase Isomaltase (-dextrinase, limit dextrinase) Maltase (-glucosidase) Lactase  Protein digestion and absorption Proteins Gastric pepsinogen (pepsin) Pancreatic trypsinogen (trypsin) Chymotrypsinogen (chymotrypsin) (Pro) Carboxypeptidases (Pro) Aminopeptidases (Pro) Elastases Peptides Peptidases (brush border) Amino acids Secondary active transport depends on Na+ transport Gastric pepsinogen pepsin  Lipid digestion and absorption TAG Lingual lipase, gastric lipase, pancreatic colipase and lipase Phospholipids Phospholipases CE Cholesterol esterase Fat-soluble vitamins  Lipid digestion and absorption (Lingual lipase) (Gastric lipase) (Bile salts) (Cholecystokinin) (pancreatic (Cholecystokinin) lipase) Processing of dietary lipids in the stomach Lingual lipase (lingual gland) & gastric lipase  Begin breaking down TAG containing short & medium chain fatty acids  Significant role in infants in breaking down milk fat The hormone Cholecystokinin (CCK) is released by enterocytes:  Acts on gallbladder to release bile salts  Stimulates pancreas to release lipases  Emulsification in the small intestine Increases the surface area of the hydrophobic lipid droplets for lipase action Caused by peristalsis and bile salts Micelles Non polar end Digestion mixture: Polar end 1. Free fatty acids 2. 2-monoacylglycerols (MAG) + Bile salts 3. Free cholesterol Micelle Absorption of lipids by enterocytes lymph Lipoproteins (chylomicrons) Blood  Pancreas Digestive enzymes (stimulated by CCK) Alkaline fluid (stimulated by secretin) Common diseases of the pancreas Acute pancreatitis Chronic pancreatitis Carcinoma of the pancreas Cystic fibrosis  Pancreatitis Inflammation of the pancreas Autodigestion of the pancreas as a result of reflex of bile or duodenal contents into the pancreatic duct Normal Pancreatitis  Pancreatitis Acute: sudden, lasts for a short time, no permanent damage. Mild discomfort to a severe, life-threatening illness Chronic: progressive, irreversible morphologic changes and gradual fibrotic replacement of the gland (conscious palpitations of the heart)  Pancreatic carcinoma 4th most frequent form of fatal cancer Low survival rate Painful Cancer of the head of the pancreas is usually detected earlier Signs: jaundice, weight loss, anorexia, nausea Tumors of -cells hyperinsulinism Gastrinomas Zollinger-Ellison syndrome: watery diarrhea, peptic ulcer, hyperacidity Cystic Fibrosis A genetic disorder that affects mostly the lungs but also the pancreas, liver, kidneys, and intestine. Characterized by dysfunction of mucous and exocrine glands. Autosomal recessive. Mutation in cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR is involved in production of sweat, digestive fluids, and mucus. Sweat test Manifestations Intestinal obstruction of the newborn Excessive pulmonary infections in childhood Pancreatogenous malabsorption in adults Sweat chloride test Measures the level of chloride in the sweat using a small electric current. Pilocarpine increases sweating + mild electric current The sweat is collected on a gauze for 30 minutes then weighed in a weighing jar Chloride >60 mEq/L →cys c fibrosis Sweat test Digestive problems in pancreatic disease Exocrine pancreatic insufficiency: malabsorption (Carbohydrate, fat, protein). Blockage of bile duct: cholestasis  liver disease Treatment: Pancreatic enzyme supplementation Laboratory findings in pancreatic disease oIncreased amylase and lipase oIncreased triglycerides oHypercalcemia (hyperparathyroidism) oHypocalcemia oHypoproteinemia oTissue hypoxia Diagnostic tests of pancreatic disorders Blood tests: Amylase, lipase, trypsin Secretin Stimulation Test (ability of pancreas to respond to secretin) Fecal Elastase Test Computed Tomography (CT) Scan With Contrast Dye Abdominal ultrasound Endoscopic Retrograde Cholangiopancreatography (ERCP) Endoscopic ultrasound Magnetic Resonance Cholangiopancreatography (MRCP) Serum amylase Among healthy individuals, the pancreas and the salivary Electrophoresis glands account for almost all pancreatic serum amylase, 40-45% from the pancreas and 55-60% from the salivary glands. salivary Small size. Can be readily filtered by the kidney The major limitation of using serum amylase measurement in diagnosing pancreatitis is the lack of specificity. Amylase and Lipase in acute pancreatitis Amylase and Lipase Lipase: (preferred test) ◦ More specific than amylase particularly for acute pancreatitis. ◦ Levels start to rise within 4 to 8 hours of the onset of pancreatitis symptoms and typically return to normal within a week. ◦ Acute pancreatitis is diagnosed if the lipase level reaches 3 times above the upper limit of normal. ◦ As chronic pancreatitis gets worse, lipase levels may be normal or decreased. Amylase: ◦ While sensitive, it is not specific. That means an elevated amylase level may indicate a problem, but the cause may not be related to the pancreas. ◦ Levels start to rise 4 to 8 hours after the onset of acute pancreatitis symptoms and typically return to normal within a week. ◦ Acute pancreatitis is likely if the level reaches 3 times above the upper limit of normal. ◦ Amylase also may be monitored in people with chronic pancreatitis. It will often be moderately elevated until the cells that make it become damaged, at which point blood levels of amylase may be decreased. Malabsorption Decreased ability to digest and/or absorb nutrients from food. Deranged absorption of electrolytes, water, vitamins (particularly fat-soluble) and minerals Seen with a variety of diseases Can lead to general malnutrition or to symptoms associated with deficiencies in specific nutrients, eg Vitamin B12, lactose Causes Digestive problems Bile insufficiency (liver disease) Pancreatic enzyme insufficiency (pancreatic disease) Cystic fibrosis Absorption problems Damage to the intestinal cells and tissues Shortened intestines due to surgery Transport problems Problems with the lymphatic system (lymphoma, abetalipoproteinemia) Steatorrhea Carbohydrate Malabsorption Defect of disaccharidases. Hereditary or acquired Indigestible carbohydrates Excess gas production (H2, CO2, CH4, abdominal discomfort, and often diarrhea Tolerance test (H2 in the breath) 35% of adults are lactase persistent Genetically G determined Autosomal recessive inheritance Genetically determined ◦ Intestinal infection (bacterial, parasitic) ◦ Inflammation (celiac disease, crohn’s disease) ◦ Preterm birth (immaturity of the enzyme) Autosomal recessive inheritance Lactose Intolerance diagnosis Hydrogen breath test Lactose tolerance blood test Stool acidity test Enzyme measurement and mutation detection Hydrogen Breath Test (HBT): Tests metabolism of intestinal bacteria Patient variation, some patient produce methane more than H2 Fructose or Basal H2 / lactose or Measure H2 / methane glucose methane for 2-3 hrs Increased gas production is observed in: - Fructose malabsorption - Lactose malabsorption - Small Intestinal Bacterial Overgrowth (SIBO) Lactose tolerance blood test Blood glucose levels are measured before, at 30 minutes, and at 60 minutes after taking 50g of lactose. Since lactose is normally broken down to glucose and galactose, taking the lactose drink would normally lead to absorption of this glucose and result in an increase in blood glucose. In persons with lactose intolerance, there is inadequate breakdown of lactose and so this rise in blood glucose is not seen. Stool acidity test Usually performed on infants or small children, as they are not eligible for other tests. Undigested lactose will create lactic acid and other short- chain fatty acids that can be detected in stool. Protein malabsorption Pancrea c disease → deficiency of pancrea c peptidases Secondary (chronic pancreatitis, cystic fibrosis, surgical removal of pancreas) Protein losing enteropathy Excessive leakage of plasma proteins into the lumen of the gastrointestinal tract. Loss of body protein  hypoalbuminemia  generalized edema and ascites. Can be caused by: Celiac disease Crohn’s disease Short bowl syndrome Others  Kwashiorkor Results from lack of protein in the diet Affects slightly older children Hypoalbuminemia → edema Fatty liver Anemia ↓ immune func on → infec ons Lipid Malabsorption Loss of lipid in feces (Steatorrhea) Vitamin A, D, E & K deficiency Pancreatic juice Bile Intestinal Mucosal cells