Introduction to Human Physiology (AP 151) Lecture Outline I. Physiology of Chemical Digestion and Absorption A.

Carbohydrate Digestion and Absorption 1. Digestion a. Salivary amylase in saliva Digests polysaccharides to maltose (a disaccharide) through hydrolysis Digests polysaccharides to maltose Digest disaccharides to monosaccharides (glucose, galactose, fructose) b. Pancreatic amylase in pancreatic juice c. Brush border enzymes (lactase, maltase, sucrase) associated with small intestine 2. Absorption a. Glucose and galactose via cotransport with Na+ ; fructose via facilitated diffusion 3. Transported to the liver via the hepatic portal vein B. Protein Digestion and Absorption 1. Digestion a. Pepsin from chief cells in gastric glands of stomach 1) HCl converts pepsinogen (inactive) to pepsin (active) 2) Converts proteins to large polypeptides b. Pancreatic enzymes (trypsin, chymotyrpsin, carboxypeptidase) 1) Trypsinogen converted to active trypsin by enterokinase (a BBE) 2) Trypsin activates chymotrypsinogen and procarboxypeptidase into chymotrypsin carboxypeptidase 3) Digest large polypeptides to small polypeptides or peptides c. Brush border enzymes (aminopeptidases, carboxypeptidases, dipeptidases) 1) Digest small polypeptides to amino acids (some dipeptides and tripeptides 2. Absorption a. Like carbohydrates, absorbed via cotansport with Na+ b. Transported to the liver via the hepatic portal vein C. Fat Digestion and Absorption 1. Emulsification (Pretreatment) a. Coating of large fat globules in duodenum with detergent-like bile salts forms small emulsions that are then acted upon by intestinal lipases/ divide and conquer

C. Fat Digestion and Absorption (continued) 2. DigestionAbsorption by intestinal cells a. Pancreatic lipase digests the lipids into fatty acids and monoglycerides. b. Monoglycerides and free fatty acids become associated with bile salts and lecithin (a phospholipid found in bile) to form micelles in intestinal lumen. c. Lipid substances dissociate from micelles and pass through luminal membrane by diffusion into intestinal cell (lipophilic substances) d. Triglycerides are resynthesized in intestinal cells and combined with phospholipids and cholesterol and coated with protein to form water-soluble chylomicrons. e. Chylomicrons enter lacteals of intestines and enter blood via thoracic duct. b. Lipoprotein classes
Lipoprotein class Chylomicrons Origin Intestine Destination Many organs Major lipids Triglycerides, Functions Deliver lipids of dietary origin to body cells Deliver endogenously produced Triglycerides to body cells Deliver endogenously produced cholesterol to various organs Remove and degrade cholesterol

VLDLs

Liver

Many organs

Triglycerides, Cholesterol Cholesterol

LDLs

Intravascular removal of trigly. fromVLDLs Liver and intestine

Blood vessels Liver Liver & steroidhormone producing glands

HDLs

Cholesterol

II. Regulation of the Digestive System A. Nervous Regulation 1. The enteric nervous system Consists of enteric neurons and neuroglia cells within the wall of the digestive tract Functions through local reflexes Can control peristaltic/mixing movements, blood flow without any outside influences

2. Autonomic nervous system control B. Chemical Regulation 1. Neurotransmitters such as serotonin 2. Hormones (gastrin, secretin, cholecystokinin) secreted by endocrine cells of the GI tract 3. Paracrine chemicals such as histamine influence activity of nearby cells III. Oral Secretions--Saliva A. Composition of saliva

1. Water97-99.5% 2. Salivary amylase 3. Electrolytes 4. Lysozyme: a weak antibacteraill agent 5. IgA antibodies helps prevent bacterial infection B. Control of salivary secretion 1. Mainly by parasympathetic division a. Chemoreceptors and pressoreceptors send afferents to salivatory nuclei in brainstem b. stimulation of Facial (VII) and Glossopharyngeal (IX) nerves--- secretion of watery (serous), enzyme-rich saliva IV. Gastric Physiology A. Secretions of the Stomach 1. Mucus secretion a. Soruce: Mucus neck cells and surface epithelial cells b. Functions: Protects gastric mucosa against mechanical damage and self-digestion 2. Intrinsic factor a glycoprotein a. Source: Pareital cells b. Function: Enhances Vitamin B-12 absorption in the ileum c. Lack of IF leads to pernicious anemia 3. HCl secretion a. Source: Parietal cells b. Mechanism of HCl secretion CO2 diffuses into cell, combines with H20 to formH2CO3 that dissociates into HCO3 + H+ Hydrogen ions (H+ ) actively pumped into duct of gastric gland c. Functions of HCl 1) Activation of the enzyme pepsinogen to pepsin 2) Assists in breakdown of connective tissue and muscle fibers 3) Bacteriocidal agent (along with salivary lysozyme) d. Stimuli for secretion include Acetylcholine from parasympathetic fibers and Gastrin from G cells increase intracellular calcium levels. Histamine released by ECL cells acts through cAMP (2nd messenger system All 3 chemicals cause copious amts of HCl to be secreted

4. Pepsinogen secretion a. Source: Chief cells b. Activation 1) By HCl; see 3c. above 2) Autocatalysis: i.e., activation of inactive pepsinogen by pepsin c. Function 1) Protein digestion 5. Endocrine secretions a. ECL cells secrete Histamine; stimulates parietal cells b. G cells secrete hormone gastrin; stimulates parietal, chief, and ECL cells c. D cells secrete somatostatin; inhibits parietal, G, and ECL cells C. Regulation of Gastric Function 1. Cephalic phase occurs before food enters the stomach a. Sight, smell, and taste of food stimuates vagus nuclei in brain b. Vagus stimulates acid secretion 1) Indirect stimulation of parietal cells (major effect) 2) Stimulation of gastrin secretion (lesser effect) 2. Gastric phase occurs once food reaches the stomach a. Distension of stomach stimulates vagus nerve; vagus stimulates acid secretion b. Most important stimuli are distension, peptides, and low acidity. b. Amino acids and peptides in lumen stimulate acid secretion 1) Direct stimulation of parietal cells (lesser effect) 2) Secretion of gastrin by G cells; gastrin stimulates acid secretion (major effect) Also activated by neural reflexes c. Gastrin secretion (by G cells) inhibited when pH of gastric juice falls below 2 3. Intestinal phase a. Includes an excitatory phase and an inhibitory phase b. Excitatory is brief and due to intestinal gastrin stimulating continued gastric gland activity c. Inhibitory phase (Enterogastric Reflex) triggered in response to: 1) Distension of duodenum 2) Increase in osmolarity of duodenum chyme 3) Fat in chyme c. Enterogastrones include 1) Somastostatin from intestine, brain, and stomach; inhibits gastric secretion of all products; inhibits gastric motility and emptying. 2) Secretin from intestinal mucosa; inhibits gastric gland secretion and motility

3) Glucagon-like peptide-1 (GLP-1) secreted by ileum and colon - stimulate pancreas to anticipate a rise in blood glucose by secreting insulin even before glucose has been absorbed into the blood V. Pancreatic Secretions A. Review of structure 1. Endocrine secretions from islets of Langerhans include insulin, glucagon, and somatostatin 2. Exocrine secretions from pancreatic acini include: a. trypsinogen: converted to trypsin by enterokinase (an intestinal brush border enzyme) b. chymotrypsinogen: converted to chymotrypsin by trypsin c. procarboxypeptidase: converted to chymotrypsin by trypsin d. amylase, lipases, and nucleases e. pancreatic aqueous alkaline secretion: neutralizes acidic chyme of duodenum B. Regulation of pancreatic secretion 1. Regulation by secretin a. Secretin is released by intestinal cells in response to HCl in intestine b. Secretin stimulates release of bicarbonate-rich pancreatic juice by duct cells 2. Regulation by cholecystokinin (CCK) a. CCK stimulates acini to release enzyme-rich pancreatic juice 3. Vagal stimulation a. Stimulates small amount of secretion of pancreatic juice during cephalic/intestinal phases V. Liver A. Structure 1. Hepatic plates separated by sinusoids 2. Hepatic portal system 3. Liver lobules 4. Enterohepatic circulation B. Functions of the Liver 1. Detoxification of the blood a. Phagocytosis by Kupffer cells b. Chemical alteration of biologically active molecules (hormones and drugs) c. Production of urea, uric acid and other molecules less toxic than parent compounds d. Excretion of molecules in bile 2. Carbohydrate metabolism a. Conversion of blood glucose to glycogen (glycogenolysis) and fat b. Gluconeogenesis

c. Secretion of glucose into the blood 3. Lipid metabolism a. Synthesis of triglycerides and cholesterol b. Excretion of cholesterol in bile c. Production of ketone bodies from fatty acids 4. Protein synthesis a. Production of albumin b. Production of plasma transport proteins (beta-globulins) c. Production of clotting factors (fibrinogen, protrhombin, and others) 5. Bile production and secretion a. Synthesis of bile salts b. Conjugation and excretion of bile pigment (bilirubin) C. Regulation of Bile Secretion 1. Continuous secretion of bile 2. Secretin and CCK augment bile secretion following a meal a. Secretin stimulates bicarbonate secretion into bile b. CCK enhances effect of secretin