Human Physiology Chap 18

Introduction into the Digestive System

Digestion and absorption are the primary functions of the digestive system. The functions of the digestive system include;

1) Motility → refers to the movement of food through the alimentary tract through the actions of several processes.

• Ingestion - Taking food into the mouth

• Mastication - Chewing the food and mixing it with saliva

• Deglutition - Swallowing food

• Peristalsis and segmentation - rhythmic wavelike contractions (peristalsis) and mixing contractions in different segments (segmentation) move food through the alimentary tract

2) Secretion → includes both exocrine and endocrine secretions

• Exocrine secretions - water, hydrochloric acid, bicarbonate, and many digestive enzymes are secreted into the lumen of the alimentary tract.

• Endocrine secretions - the stomach and small intestine secrete a number of hormones that help regulate the digestive system.

3) Digestion → refers to the breakdown of food molecules into smaller subunits to be absorbed.

4) Absorption → refers to the passage of digested end products into the blood or lymph

5) Storage and elimination → refers to the temporary storage and elimination of indigestible food molecules.

6) Immune barrier → the simpler columnar epithelium that lines the intestine, provides a physical barrier to the penetration of pathological organisms and their toxins. There is also cells of the immune system reside in the connective tissue located just under the epithelium to promote immune responses.

The digestive system can be divided into the alimentary / gastrointestinal (GI) and accessory digestive organs.

Mucosa

Mucosa lines the lumen of the alimentary tract. It is absorptive and a major secretory layer. It consists of simple columnar epithelium, tiny channels for ions, and zonula adherens junctions beneath tight junctions. This is the muscle layer responsible for the numerous small folds in certain portions of the alimentary tract. These folds greatly increase the absorptive surface area. Specialized cells in the mucosa secrete mucus through most of the alimentary tract.

Submucosa

The thick submucosa is a highly vascular layer of connective tissue that serves the mucosa. Absorbed molecules that pass through the columnar epithelial cells of the mucosa enter the blood and lymphatic vessels of the submucosa. It contains blood vessels, glands, and nerve plexuses. The submucosa plexus provides nerve supply to the small and large intestine.

Muscularis

The muscularis is responsible for the segmental contractions and peristaltic movement through the alimentary tract. Contractions of the layers within the muscularis move the food through the tract and physically pulverize and mix the food with digestive enzymes. The myenteric plexus provides the major nerve supply to the entire alimentary tract.

Serosa

The outer serosa completes the wall of the alimentary tract. The peritoneum has both a visceral and parietal layer.

From mouth to stomach

Mastication (chewing) of food mixes it with saliva that is secreted by the salivary glands. Saliva contains salivary amylase, an enzyme that can catalyze the partial digestion of starch. Deglutition (swallowing) is divided into three phases, oral, pharyngeal and esophageal.

Swallowing is a complex activity, requires coordinated 25 pairs of muscles in the mouth. The muscles of the mouth are striated and innervated by somatic motor neurons where the muscles of the middle and lower esophagus are smooths and innervated by autonomic neurons. The oral phase is under voluntary control while the pharyngeal and esophageal phases are automatic and controlled by the swallowing center in the brain stem. In the oral phase muscles of the mouth and tongue mix food with saliva and create a bolus → rounded mass to be swallowed of food, that the tongue muscles move toward the oropharynx.

Esophagus

The esophagus is a portion of the GI tracts that connects the pharynx to the stomach. Before terminating in the stomach the esophagus passes through the diaphragm by means of an opening called the esophageal hiatus. The upper third of the esophagus contains skeletal muscle, the middle third contains a ix of skeletal and smooth muscle, and the terminal portion contains only smooth muscle.

Swallowed food is pushed from oral to anal via wavelike muscle contractions called peristalsis.

The lumen of the terminal portion of the esophagus is slightly narrows because of a thickening of circular muscle fibers in its wall. This portion is called the lower esophageal sphincter, it relaxes to allow peristaltic waves of contraction in the esophagus to push food into the stomach. After food passes into the stomach, constriction of the muscle fibers of this region help prevent the stomach contents from regurgitating into the esophagus.

Stomach

The stomach is the most distensible part of the GI tract. It is continuous with the esophagus superiorly and empties into the duodenum of the small intestine inferiorly. The functions of the stomach are to store food, initiate the digestion of proteins, to kill bacteria, and move food into the small intestine as a pasty material called chyme.

Swallowed food from the esophagus is delivered to the cardiac region of the stomach. Contractions of the stomach churn the chyme, mixing it more thoroughly with the gastric secretions. The contractions also push partially digested food from the antrum through the pyloric sphincter into the first part of the small intestine.

The inner surface of the stomach is thrown into long folds called rugae. Microscopic examination of the gastric mucosa shows it is folded. The openings of the folds into the stomach lumen are called gastric pits. The cells that line the folds secrete various products into the stomach and these cells form the exocrine gastric glands.

There are several types of cells in the gastric glands that secret different productions.

1) Mucous neck cells → secrete mucus

2) Parietal cells → secrete hydrochloric acid (HCl) and intrinsic factor

3) chief/zymogenic cells → secrete pepsinogen, which is an inactive form of the protein digesting enzyme pepsin

4) Enterochromaffin-like cells → secrete histamine and serotonin as paracrine regulators of the GI tract

5) G cells → secrete gastrin into the blood

6) D cells → secrete somatostatin

7) P/D1 cells → secrete ghrelin, the secretion of this hormone rises before meals and typically falls after meals. Helps regulate hunger and body weight.

The only stomach function essential for life is the production of intrinsic factor, a glycoprotein needed for intestinal absorption of vitamin B necessary for the normal development of red blood cells in bone marrow.

The exocrine secretions of gastric cells combined with water form gastric juice.

Pepsin and Hydrochloric Acid Secretion

Carriers known as H/K ATPase pumps, transport H uphill against million to one concentration gradient into the lumen of the stomach while they transport K into the opposite direction. In potassium recycling, the K inside the parietal cell then leaks out through K channels to prevent depletion of K in the gastric lumen. The surface of parietal cell has numerous microvilli with a high surface area to allow the insertion of a large number of H/K pumps.

Digestion and Absorption in the Stomach

Proteins are only partially digested in the stomach by the action of pepsin while carbohydrates and fats are not digested at all by pepsin. The complete digestion of food molecules occurs later when chyme enters the small intestine.

Almost all of the products of digestion are absorbed through the wall of the small intestine. Absorption occurs as a result of the lipid solubility of molecules.

Gastritis and Peptic Ulcers

Peptic ulcers are erosions of the mucosa of the stomach or duodenum that penetrate through the muscular mucosa layer.

Small Intestine

The small intestine is the portion of the GI tract between the pyloric sphincter of the stomach and the ileocecal valve opening into the large intestine. It is the longest part of the GI tract but is considered small because of its diameter. The first 10 inches extending from the pyloric sphincter is the duodenum, the next two fifths of the small intestine is the jejunum and the last three fifths is the ileum.

The products of digestion are absorbed across the epithelial lining of the intestinal mucosa. Absorption occurs at a rapid rate as a result of extensive folding’s of the intestinal mucosa. The mucosa and submucosa form large folds called plicae circulares. The surface area is further increased by microscopic folds of mucosa called villi, and by folding’s of the apical plasma membrane of epithelial cells called microvilli.

Villi and Microvilli

Each villus is a fingerlike fold of mucosa that projects into the intestinal lumen. The villi are covered with columnar epithelial cells and mucus secreting mucus cells.

Microvilli are formed by folding’s at the apical surface of each epithelial plasma membrane.

Intestinal Enzymes

The plasma membranes of the microvilli contain digestive enzymes. These brush border enzymes are not secreted into the lumen but instead remain attached to the plasma membrane with their active sites exposed to the chyme. Enterokinase / enteropeptides is required for the activation of the protein digesting enzyme.

Intestinal Contractions and Motility

Two types of contractions occur in the small intestine; peristalsis and segmentation. Peristalsis is much weaker in the small intestine versus the esophagus and stomach.

The major contractile activity of the small intestine is segmentation → refers to the muscular constrictions of the lumen which occur simultaneously at different intestinal segments. This is to mix the chyme more thoroughly.

Contractions of the intestinal smooth muscles occur automatically in response to endogenous pacemaker activity. In intestinal smooth muscle the rhythm of contractions is placed by graded depolarizations called slow waves. The slow waves are produced by unique cells, identified as interstitial cells of Cajal. They have gap junctions that conduct depolarization from one cell to the next, so the entire muscularis functions as a single unit.

Slow waves spread by ay of gap junctions between the interstitial cells of Cajal. The slow waves can only spread only a short distance and must be regenerated by the next pacemaker region, producing segmented contractions of the intestine.

The slow waves produced and conducted by the interstitial cells of Cajal serve to depolarize the adjacent smooth muscle cells. The slow wave depolarization exceeds a threshold value it triggers action potentials in the smooth muscle cells by opening voltage gated Ca Channels. Producing Ca action potentials on the tops of the slow wave depolarizations. The inward flow of Ca has two effects;

1) produces the upward depolarization phase of the action potential

2) it stimulates contraction

Autonomic nerves modify the automatic contractions of the intestine large by influencing the enteric nervous system which stimulates/inhibits the ICC and intestinal smooth muscle cells.

Large Intestine

The large intestine or colon extends from the ileocecal valve to the anus framing the small intestine. Chyme from the ileum passes into the cecum → blind pouch (open only at one end), at the beginning of the large intestine. Waste material then passes in sequence through the ascending colon, transverse colon, descending colon, sigmoid colon, rectum, and anal canal. Waste material is excreted through the anus → the external opening of the anal canal.

The mucosa of the large intestine, contains many scattered lymphocytes and lymphoid nodules and is covered by columnar epithelial cells and mucus secreting goblet cells. There is no villi in the large intestine, the intestinal mucosa is flat. It has an external layer of smooth muscle known as taenia coli. Since the muscle is shorter than the length of the colon, it bunches to form pouches known as haustra.

The large intestine has little or no digestive function but it does absorb water and electrolytes from the remaining chyme as well as vitamins.

Intestinal Microbiota

Microorganisms are present in relatively small numbers in the stomach and the proximal portion of the small intestine. The numbers increase in the distal ileum and greatest in the colon. There are several thousand different species of microorganisms, great diversity they contain about 100 times more genes then host human cells. These are known as intestinal microbiota microflora, or human microbiome.

In the colon the intestinal microbiota are comprised mostly of anaerobic bacterial species. The microbiota are described as commensal bacteria → refers to a relationship where one species benefits and the other is neither benefited nor harmed.

Humans provide the bacteria with nutrients and anaerobic home in the large intestine, and they provide a variety of benefits. Like helping us provide us with vitamins that get absorbed in the colon. The commensal bacteria also contains enzymes that digest dietary fiber, so polysaccharides that cannot be hydrolyzed by our digestive enzymes into monosaccharides.

Bacteria ferment the sugars obtained from fiber into short chain fatty acids which are then used for energy by colonic epithelial cells and are absorbed into the portal vein blood. These short chain fatty acids help promote intestinal motility and secretion. They also help retain nutrients, electrolytes, and water from the colon contents.

Bile Production and Secretion

The liver produces 250 -1500 ml of bile per day. Bile pigment or bilirubin is produced in the spleen, liver, and bone marrow as a derivative of the heme groups from hemoglobin known as biliverdin. After the conversion from biliverdin to bilirubin the free bilirubin is not water soluble so it gets carried in the blood attached to albumin proteins. The protein bound bilirubin can neither be filter by the kidneys nor directly excreted by the liver into the bile.

The liver can take some of the free bilirubin out of the blood and combine it with glucuronic acid, which then turns into conjugated bilirubin → which is water soluble and can be turned into bile.

Bile acids are derivatives of cholesterol that have two-four polar groups on each molecule making them amphipathic. The primary bile acids in humans are cholic acid and chenodeoxycholic acid, which are mixed with amino acids or taurine to form bile salts. The bile salts are then converted by the primary bile acids into the secondary bile acids deoxycholic acid and lithocholic acid.

The livers production of bile acids from cholesterol is the major pathway of cholesterol breakdown in the body.

Detoxication of the Blood

The hepatocytes lining the sinusoids, Kupffer cells, and dendritic cells of the liver have PAMPs enabling them to scavenge blood borne bacteria. The liver can also remove hormones drugs and other biologically active molecules from blood by 1) excreting of the compounds through bile, 2) phagocytosis by the Kupffer cells that line the sinusoids, 3) chemical alteration of these molecules within the hepatocytes

Secretion of Glucose, Triglycerides and Ketone Bodies

The liver helps regulate the blood glucose concentration by removing glucose from the blood or adding glucose to it according to the needs of the body. The glucose can be derived from the breakdown of stored glycogen in a process → glycogenolysis. Or it can be produced by the conversion of noncarbohydrate molecules into glucose in a process called gluconeogenesis. The liver contains enzymes required to convert free fatty acids into ketone bodies (ketogenesis) which are secreted into the blood in large amounts during fasting.

Gallbladder

The gallbladder is a saclike organ attached to the inferior surface of the liver. It stores and concentrates bile, which it then drains it from the liver through bile, hepatic, and cystic ducts. Contraction of the muscularis layer of the gallbladder ejects bile through the cystic duct into the common bile duct which conveys buke into the duodenum.

Pancreas

The pancreas is a soft glandular organ that has both exocrine and endocrine functions. The endocrine functions is performed by clusters of cells called the pancreatic islets. They secrete hormones of insulin and glucagon into the blood. As an exocrine gland the pancreas secretes pancreatic juice through the pancreatic duct into the duodenum. Within the lobules of the pancreases are the exocrine secretory units → pancreatic acini.

Pancreatic Juice

Pancreatic juice contains bicarbonate and 20 different digestive enzymes. This includes; 1) amylase → digest starch, 2) trypsin → digests protein, 3) lipase → digests triglycerides . The complete digestion of food molecules in the small intestine requires the action of both pancreatic enzymes and brush border enzymes in the small intestine.

The pancreatic acini secrete inactive enzymes in an isotonic saline solution while the cells that line the ductules absorb Cl and secrete bicarbonate.

Most pancreatic enzymes are produced as inactive molecules or zymogens, so the risk of self digestion within the pancreas is minimized.

Regulation of The Digestive System

Neural and endocrine control mechanisms modify the activity of the digestive system. The GI tract is both an endocrine gland a target for the action of various hormones.

Gastric motility and secretion are both to some extent automatic. The effects on autonomic nerves and hormones are super imposed on automatic activity. The extrinsic control of stomach function is divided into three phases 1) cephalic phase, 2) the gastric phase 3) the intestinal phase.

Cephalic Phase

The cephalic phase of gastric regulation refers to control by the brain via the vagus nerve. The activation of the vagus nerves stimulates the chief cells to secrete pepsinogen. Neurotransmitters released by the vagus also stimulate the secretion of HCl by parietal cells. The vagus stimulates G cells to secrete gastrin → that then enters the circulation and acts a s a hormone to stimulate the ECL cells to secretion histamine. The histamine then functions as a paracrine regulator stimulate the parietal cells to secrete HCl.

Gastric Phase

The arrival of food into the stomach stimulates the gastric phase of regulation. Gastric secretion is stimulated in response to two factors; 1) distension of the stomach → which is determined by the amount of chyme. 2) The chemical natural of the chyme. These stimuli act primarily via the secretion of gastrin.

Intestinal Phase

The intestinal phase of gastric regulation refers to the inhibition of gastric activity when chyme enters the small intestine.

Enteric Nervous System

The neurons and neuroglia of the enteric nervous system (ENS) consists of enteric neurons → those within the intestine, organized into ganglia that are interconnected via two plexuses and their supporting neuroglia, known as → enteric glial cells.

Peristalsis is regulation by the ENS. Extrinsic afferents together with the different peptide hormones released from the intestine alert the brain to the conditions in the gastrointestinal tract. This info is important in the CNS regulation of digestion and in both conscious and unconscious perceptions of food intake and the state of the viscera.

Extrinsic afferents work together with different peptide hormones released from the intestine to alert the brain to the conditions in the GI tract. This is important to the CNS regulation of digestion in both conscious and unconscious perceptions of food intake and the state of the viscera. The brain can sometimes overpower the enteric nervous system regulation during intense emotions through stimulatory parasympathetic and inhibitory sympathetic outflow from the CNS. The extrinsic vagus and sympathetic nerve motor fibers to the intestine exert their effects largely through their influence on the intrinsic neurons of the ENS.

Intestinal Reflexes

There are several intestinal reflexes that are controlled both locally → via the enteric nervous system and paracrine regulators, and extrinsically through nerves and hormones. These help different regions of the digestive tract coordinate their activities to maximize absorption of nutrients.

1) gastrolienal reflex → increased gastric activity causes increased motility of the ileum and increased movements of chyme through the ileocecal sphincter

2) ileogastric reflex → distension of the ileum causes a decrease in gastric motility

3) intestino-intestinal reflexes → over distension of one intestinal segment causes relaxation through out the rest of the intestine

Regulation of Pancreatic Juice and Bile Secretion

The arrival of chyme into the duodenum stimulates both the intestinal phase of the gastric regulation and reflex secretion of pancreatic juice and bile. Additional entry of chyme into the duodenum is slowed by the inhibitory effects of neural reflexes and enterogastrone allowing time for the previous load of chyme in the duodenum to be digested with the pancreatic juice and bile. The secretion of pancreatic juice and bile is stimulated both by neural reflexes initiated in the duodenum.

Secretion of Pancreatic Juice

The secretion of pancreatic enzymes are stimulated by ACh released by the vagus nerve and by the hormone CCK secreted by the duodenum.

The hormones secretin and CCK are secreted by the duodenum in response to different stimuli and have different primary effects. Secretion of CCK is stimulated by the protein and fat content of chyme, and then CCK stimulates the secretion of the pancreatic juice enzymes that help digest these molecules.

The secretion of secretin by the duodenum is stimulated by a fall in pH below 4.5.

Secretion of Bile

Before a meal a gallbladder starts to contract and empty due to stimulation via the vagus nerve. The liver is then stimulated to secrete more bile by the secondary bile acids that return to the liver from the intestine via the hepatic portal vein. Secretin stimulates the bile duct cells of the liver to secrete bicarbonate and water into the bile and CCK enhances this effect. After a meal chyme enters the duodenum the fat in the chyme stimulates CCK secretion. The CCK then stimulates contractions of the gallbladder allowing it to empty more bile into the duodenum → which aids fat digestion and thereby completes a negative feedback loop. The arrival of chyme in the duodenum also produces a neural reflex that supplements the action of CCK in causing contractions and emptying of the gallbladder.

Digestion and Absorption of Carbohydrates

Most carbohydrates are ingested as starch. The most commonly ingested sugars are sucrose and lactose. The digestion of starch begins in the mouth via salivary amylase. This enzyme cleaves some of the bonds between adjacent glucose molecules, through people often don’t chew their food long enough for sufficient digestion to occur in the mouth.

The digestion of starch therefore occurs mainly in the duodenum as a result of pancreatic amylase. This enzyme cleaves the chains of starch to produce disaccharide maltose and the trisaccharide maltriose.

Pancreatic amylase cannot hydrolyze the bond between glucose molecules at the branch points in starch, so oligosaccharides are released together with maltose and maltriose by the activity of this enzyme.

These are all hydrolyzed to their monosaccharides by brush border enzymes located on the microvilli of the epithelial cells in the small intestine. The brush border enzymes also hydrolyze the disaccharides sucrose and lactose into their component monosaccharides. These monosaccharides are then moved across the brush border membrane by secondary active transport.

Digestion and Absorption of Proteins

Protein digestion begins in the stomach with the action of pepsin. Pepsin digestion helps produce a more homogenous chyme but is not essential for the complete digestion of protein that occurs. Most protein digestion occurs in the duodenum and jejunum. The pancreatic juice enzymes trypsin, chymotrypsin and elastase cleave peptide bonds in the interior of the polypeptide chains.

As a result of the action of these enzymes polypeptide chains are digested into free amino acids dipeptides and tripeptides.

Digestion and Absorption of Lipids

30% of fat digestions can occur in the mouth and stomach with the aid of lingual and gastric lipases. The majority of fat is digested in the small intestine by pancreatic lipase. Through mechanisms the arrival of lipids in the duodenum serves as a stimulus for the secretion of bile.

In emulsification, bile salt micelles are secreted into the duodenum and act as detergents to break up the fat droplets into tiny emulsification droplets of triglycerides. It is not just chemical digestion, there is no hydrolyzation of the glycerol and fatty acids occurring.

Digestion of Lipids

Emulsification of fat aids its digestion because the smaller and more numerous emulsification droplets Fat digestion occurs at the surface of the droplets through the enzymatic action of pancreatic lipase → which is aided in its action by a protein called colipase that coats the emulsification droplets and anchors the lipases enzyme to them.

Absorption of Lipids

Absorbed lipids pass through the lymphatic system eventually entering the venous blood by way of the thoracic duct.

Transport of Lipids in the Blood