Introduction to Physiology: The Cell and General Physiology

Introduction to Physiology: The Cell and General Physiology

Types of Secretory Glands Single Cell - mucous cells or goblet cells Simple - indentations in epithelium (crypts of Lieberkhn) Tubular - acid secreting oxyntic gland Complex - salivary, pancreas Copyright 2006 by Elsevier, Inc. Control of Secretions Local - tactile, distention, irritation Reflex - nervous input Hormonal - G.I. hormones

Parasympathetic Stim. Sympathetic Stim. Copyright 2006 by Elsevier, Inc. rate of secretion or rate of secretion Digestive Enzymes Salivary glands -amylase ptyalin lingual lipase Stomach pepsin

Copyright 2006 by Elsevier, Inc. Pancreas amylase trypsin chymotrypsin carboxypeptidase elastase lipase-colipase phospholipase A2 cholesterol esterase

Intestinal Mucosa enterokinase sucrase maltase lactase -dextrinase (isomaltase) aminooligopeptidase dipeptidase Daily Secretion of Intestinal Juices Daily Volume (ml) 1000

Saliva 1500 Gastric secretion 1000 Pancreatic secretion 1000 Bile Small intestinal secretion 1800 Brunners gland secretion 200 200 Large intestinal secretion 6700 Total

Copyright 2006 by Elsevier, Inc. pH 6.0-7.0 1.0-3.5 8.0-8.3 7.8 7.5-8.0 8.0-8.9 7.5-8.0 Saliva Two types of secretion - Serous

- watery secretion, contains an -amylase (and ptyalin) - Mucous - contains mucin - lubrication Secrete 800-1500 ml/day of saliva Maximum rate of secretion: 4 ml/min Copyright 2006 by Elsevier, Inc.

Salivary Glands Gland Type of saliva Parotid Serous Submandibular Mucous/

Serous Sublingual Mucous/ Serous Buccal Mucous Copyright 2006 by Elsevier, Inc.

% of total Secreted 90% 10% <1% Copyright 2006 by Elsevier, Inc. Figure 64-2; Guyton & Hall Oxyntic gland from the body

of the stomach Copyright 2006 by Elsevier, Inc. Figure 64-4; Guyton & Hall Oxyntic gland from the body of the stomach Figure 64-5; Guyton & Hall Copyright 2006 by Elsevier, Inc.

Copyright 2006 by Elsevier, Inc. Downloaded from: StudentConsult (on 19 February 2010 04:59 PM) 2005 Elsevier Gastric Acid Three major functions - Bacteriostatic - Converts pepsinogen to pepsin - Begins protein digestion (with pepsin) Copyright 2006 by Elsevier, Inc. Pepsinogen

Pepsinogen is an inactive, secreted form of pepsin Acid converts pepsinogen to pepsin Pepsin (35 kDa) converts more pepsinogen to pepsin - proteolytic enzyme - optimal pH 1.8 - 3.5 - reversibly inactivated > pH 5.0 - irreversibly inactivated > pH 7-8 Copyright 2006 by Elsevier, Inc. Copyright 2006 by Elsevier, Inc. Peptic Ulcers

Peptic ulcers occur when damaging effects of acid and pepsin overcome ability of mucosa to protect itself Gastric ulcers - main problem is decreased ability of mucosa to protect itself Duodenal ulcers - main problem is exposure to increased amounts of acid and pepsin Copyright 2006 by Elsevier, Inc. Treatment of Peptic Ulcers Antacids H2 receptor blockers

- Rantidine (Zantac) - Cimetidine (Tagamet) Proton pump inhibitors - Omeparazole (Prilosec) Antibiotics Surgical (rare) - antrectomy Copyright 2006 by Elsevier, Inc. - vagotomy

Figure 65-7; Guyton & Hall Copyright 2006 by Elsevier, Inc. Pancreas As chyme floods into small intestine two things must happen: Acid must be neutralized to prevent damage to duodenal mucosa Macromolecular nutrients - proteins, fats and starch must be broken down much further so their constituents can be absorbed

Copyright 2006 by Elsevier, Inc. Pancreas Pancreas plays vital role in accomplishing both objectives Digestive enzymes for all food types Bicarbonate solution to neutralize acid chyme Copyright 2006 by Elsevier, Inc. Internal Structure of Pancreas Compound gland with structure similar to

salivary gland Acini - grape-like clusters of cells that store and secrete digestive enzymes Ducts - secrete bicarbonate Intercalated ducts - receive secretions from acini Intralobular ducts - receive fluid from intercalated ducts Copyright 2006 by Elsevier, Inc. Enzymes for Protein Digestion Proteolytic enzymes - Trypsin

- Chymotrypsin Cleaves proteins to polypeptides - Carboxypeptidase Cleaves polypeptides to AA Copyright 2006 by Elsevier, Inc. Enzymes for Carbohydrate Digestion

Pancreatic amylase - starches - glycogen to disaccharides Copyright 2006 by Elsevier, Inc. Enzymes for Fat Digestion Pancreatic lipase fat fatty acids +monoglycerides Phospholipase phospholipids fatty acid Cholesterol esterase cholesterol esters fatty acid

Copyright 2006 by Elsevier, Inc. Why Doesnt the Pancreas Digest Itself? Pancreatic proteolytic enzymes are stored and secreted in an inactive form - (also, a trypsin inhibitor is present in cells) trypsinogen trypsin chymotrypsinogen chymotrypsin procarboxypeptidase carboxypeptidase

Copyright 2006 by Elsevier, Inc. Activation of Proteolytic Enzymes Trypsinogen enterokinase Trypsin Enterokinase - located on intestinal mucosal cells Trypsin - autocatalytic activation - activates

- chymotrypsinogen, - procarboxypeptidase - trypsinogen Copyright 2006 by Elsevier, Inc. Trypsin Inhibitor Enzyme precursors stored in cells along with trypsin inhibitor Trypsin inhibitor prevents formation of trypsin - in acini - in ducts Acute pancreatitis - a primary lack of trypsin inhibitor - not enough trypsin inhibitor is present

Copyright 2006 by Elsevier, Inc. Bicarbonate Neutralizes Acid Chyme Secretin induced bicarbonate secretion neutralizes acid chyme creating optimal conditions (pH = 7-8) for digestive enzymes CO2 HCl + NaHCO3 NaCl + H2CO3 H2O Secretin is natures antiacid Copyright 2006 by Elsevier, Inc.

Model of Bicarbonate Secretion 1. CO2 combines with H2O in presence of C.A. in cell 2. Carbonic acid dissociates into HCO3- and H+ ions 3. H+ ions are transported through apical membrane by secondary transport mechanism that requires Na+ gradient. Na+ gradient is established by usual Na + -K + ATPase pump. 4. HCO3- moves out of cell in exchange for Cl -. Copyright 2006 by Elsevier, Inc. BLOOD

DUCT CELL LUMEN ClClHCO3- ClS 4 H2O CO2 3

H+ Na+ K Copyright 2006 by Elsevier, Inc. K + Na+ ,H2O

1 C.A. HCO3+ 2 H 2O 6 +

S P H+ + HCO3- Na+ K+ Na+ , H2O Model of Bicarbonate Secretion (contd) 5. Rate of HCO3- secretion is dependent upon luminal Clconcentration.

6. Na+ moves down electrochemical gradient. Water moves into lumen establishing osmotic equilibrium. (Pancreatic juice is always isotonic.) Secretin - acts to open Cl- channels and thus increase secretion of bicarbonate. Copyright 2006 by Elsevier, Inc. Effect of Secretion Rate on Ionic Composition of Pancreatic Juice Low secretion rates bicarbonate concentration is low chloride concentration is high

High secretion rates bicarbonate concentration is high chloride concentration is low Sodium and potassium concentrations always same as plasma Copyright 2006 by Elsevier, Inc. Regulation of pancreatic secretion

Figure 64-10; Guyton & Hall Copyright 2006 by Elsevier, Inc. Regulation of Pancreatic Secretion Secretion of fluid and HCO3- is mainly dependent upon amount of acid entering duodenum Secretion of enzymes is mainly dependent upon amount of fat and protein entering duodenum Acetylcholine - vagovagal reflexes Cholecystokinin - fat and protein Secretin Copyright 2006 by Elsevier, Inc.

- acid Mainly enzymes Fluid / HCO3- Phases of Pancreatic Secretion Cephalic (20%) Gastric (5-10%) Both phases mediated by vagus low volume, high enzyme secretion

Intestinal (70-80%) acid secretin HCO3- /H2O fat/protein CCK enzymes acid/fat/protein vagovagal Ach enzymes CCK and acetylcholine both potentiate the effects of secretin on water and bicarbonate secretion. Copyright 2006 by Elsevier, Inc.

Pancreatic HCO3- Output (Secretin) Response to Duodenal Acidification Secretin released when pH < 4.5. Below pH = 3, secretin release is maximal in segment of duodenum. Further release of secretin depends upon area of small intestine affected. (Maximal bicarbonate response is 30 mEq/hr) During meal pH rarely < 3.5 or 4.0. Copyright 2006 by Elsevier, Inc.

Distribution of GI Hormones Digestive products are equally effective in releasing secretin when applied to any part of duodenum or jejunum. Fundus Antrum Secretin Copyright 2006 by Elsevier, Inc. Duo Jejun Ileum Colon

Pancreatic Failure Digestion is abnormal when pancreas fails to secrete normal amounts of enzymes. Pancreatitis Removal of pancreatic head - malignancy Without pancreatic enzymes 60% fat not absorbed (steatorrhea) 30-40% protein and carbohydrates not absorbed Copyright 2006 by Elsevier, Inc. Pancreatitis Pancreatitis means inflammation of pancreas.

Autodigestion theory can explain condition. Chronic pancreatitis - (multiple shared causes) alcohol - most common cause in adults cystic fibrosis - most common cause in children Acute pancreatitis - (multiple shared causes) gallstones Copyright 2006 by Elsevier, Inc. - most common cause Secretion Failure in Cystic Fibrosis

CF patients lack chloride transporter at apical membrane. Watery ductal secretion decreases which concentrates acinar secretions in ducts. Precipitation of proteinaceous secretions block ducts and can destroy gland by autodigestion. Copyright 2006 by Elsevier, Inc. Copyright 2006 by Elsevier, Inc.

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