GENERAL PRINCIPLES OF G.I. FUNCTION – MOTILITY, NERVOUS CONTROL, BLOOD CIRCULATION
JOAQUIN A. MORENO, M.D.
DIPLOMATE IN INTERNAL MEDICINE AND GASTROENTEROLOGY
Processes involved in providing continual supply of nutrients, electrolytes and water to the body:
1) Movement of food to GIT
2) Secretion of digestive juices and food digestion
3) Absorption of digestive products, water, electrolytes
4) Circulation of blood thru GI organs to carry away absorbed substances
5) Nervous and hormonal control of these functions
Layers of Intestinal Wall from Outer Surface Inwards
2) Longitudinal muscle layer
3) Circular muscle layer
¨ Smooth muscle fiber 200-500 micrometers long; 2-10 micrometer in diameter; arranged in bundles of 1000 parallel fibers.
¨ Longitudinal muscle layer – extends longitudinally down GIT.
¨ Circular muscle layer – extends around the gut.
¨ Electrical signals that initiate muscle contraction can travel from one fiber to the next within each bundle more rapidly along its length than sideways.
¨ Each muscle layer functions as a SYNCYTIUM. When an action potential is elicited anywhere in a muscle mass, it travels in all directions in the muscle.
¨ Distance traveled by action potential depends on muscle excitability – few mm to cm or entire length of GIT.
¨ Connections exist between longitudinal and circular muscle layers. Excitation of one often excites the other.
Electrical Activity of GI smooth muscle
2 basic types of electrical waves
1) Slow waves
¨ Slow waves – slow undulating changes in resting membrane potential; these waves are not action potentials; determines rhythm of most of GI contractions
Frequency of Slow Waves
3 / min – body of stomach
12/ min duodenum
8-9/min – terminal ileum
¨ Spikes – true action potentials; occur automatically when RMP becomes more positive than –40 mV
¨ Changes in resting membrane potential voltage
¨ Depolarization – RMP becomes less negative; muscle fibers more excitable
¨ Hyperpolarization – RMP becomes more negative; fibers less excitable
Factors that Depolarize the Membrane
1) Muscle stretching
2) Acetylcholine stimulation
3) Parasympathetic nerve stimulation à acetylcholine secretion
4) Stimulation by GI hormones
Factors that Hyperpolarize the Membranes
1) Norepinephrine or epinephrine stimulation.
2) Sympathetic nerve stimulation that secrete norepinephrine.
¨ Calcium Ions and Muscle Contraction
Ca ++ à calmodulin control mechanisms à activate myosin filaments à myosin –actin attractive forces à muscle contraction
Enteric nervous system – neural control of GI function
¨ Lies entirely in the gut wall.
¨ Begins in esophagus, extends to anus.
¨ Controls GI movement and secretion.
Enteric nervous system composed of 2 plexuses
1) Myenteric or Auerback plexus
2) Meissner’s or submucosal plexus
¨ Myenteric plexus – outer, lying between longitudinal and circular muscle layers; controls mainly GI movements.
¨ Meissner’s Plexus – lies in submucosa; controls mainly GI secretion and local blood flow.
Simulation of Myenteric Plexus results in:
1) Increased tonic contraction (increased tone of gut wall).
2) Increased intensity of rhythmic contraction.
3) Increased velocity of conduction àmore rapid peristaltic wave.
Neurotransmitter Substances Released by Enteric Neuron
1) acetylcholine – excites GI activity
2) Norepinephrine – inhibits GI activity
7) Substance P
8) VIP ( vasoactive intestinal peptide)
Autonomic Control of GIT
1) Parasympathetic innervation
2) Sympathetic innervation
¨ Parasympathetic – divided into cranial and sacral divisions
¨ Cranial – innervates esophagus , stomach, pancreas up to first half of large intestines
¨ Sacral – innervates sigmoid , rectum, anus à defecation reflex
¨ Parasympathetic stimulation causes a general increase in activity of enteric nervous system , enhancing activity of most GI functions
¨ Sympathetic – innervates all portion of GIT; secretes mainly norepinephrine, inhibits activity of GIT
Afferent nerve fibers from the GUT
Can be stimulated by:
1) irritation of gut mucosa
2) excessive distension of Gut
3) specific chemical substances in gut
3 types of GI reflexes
1) Reflexes integrated entirely within enteric NS
a) control GI secretion, peristalsis, mixing contractions
2) Reflexes from gut to prevertebral sympathetic ganglia back to GIT
a. Gastrocolic – signal from stomach cause evacuation of colon.
b. Enterogastric – signals from colon and small intestine inhibit stomach motility and secretion.
c. colonoileal – reflexes from colon to inhibit emptying ileal contents into colon
3) Reflexes From Gut to Spinal Cord or Brain Stem Then Back to GIT
a) reflexes that control gastric motor and secretory activity
b) reflexes that cause general inhibition of entire GIT
c) defecation reflexes
Hormonal Control of GI Motility
– “I” cells in duodenal and jejunal mucosa; secreted in response to breakdown products of fat, fatty acids in intestines
– Increases GB contractility, expelling bile into SI, emulsifying fatty substances, allowing them to be digested and absorbed.
– Inhibits gastric motility, slowing emptying of food from stomach to give adequate digestion of fats in upper intestinal tract.
– Secreted by “S” cells in duodenum in response to gastric juice emptying into duodenum; mild inhibitory effect on GI motility.
¨ Gastric inhibitory peptide (GIP)
– Secreted by mucosa of upper small intestine in response to FA and AA, less to CHO.
– Decreases motor activity of stomach; slows emptying of gastric contents into duodenum when upper SI overloaded with food.
Functional types of movements in GIT
¨ Propulsive – cause food to move forward along GIT at rate appropriate for digestion and absorption.
¨ Mixing – keep intestinal contents thoroughly mixed at all times.
– Basic propulsive movement of GIT; stimulation at any point causes contractile ring to appear in circular muscle spreading along the tube.
– Occurs in GIT, bile ducts, other glandular ducts, ureters.
¨ Distension of the GUT – usual stimulus for peristalsis.
¨ Large amount of food in gut à stretch of wall à stimulate enteric NS à gut contraction 2-3 cm behind stretched wall à contractile ring initiate peristalsis.
¨ Other stimulus that initiates peristalsis – chemical or physical irritation of gut lining, parasympathetic nerve signals.
¨ Law of the GUT – peristaltic reflex + anal direction of peristaltic movement.
¨ Mixing movements – occur when
1) Forward progression of intestinal contents blocked by sphincter causing churning rather than propulsion.
2) Local intermittent constrictive contractions occur every few cm causing “chopping” and “shearing” of intestinal contents.
- Extensive system of bv of GIT which includes blood flow thru gut + spleen, pancreas, liver.
¨ Blood from gut, spleen and pancreas à portal vein à liver à sinusoids à hepatic vein à vena cava.
¨ Reticuloendothelial cells in liver sinusoids remove bacteria and other harmful agents that might enter blood stream from GIT.
¨ Blood flow in each area of GIT is directly related to the level of local activity.
¨ During active absorption of nutrients, blood flow in the villi and adjacent submucosa is increased.
¨ During increased motor activity, blood flow in muscle layers of intestinal wall increases.
¨ After a meal, motor, sensory and absorptive activity is all increased.
Possible causes of increased blood flow during intestinal activity:
1. Several vasodilator substances mostly peptide hormones are released from the mucosa during digestion (cholecystokinin, VIP, gastrin, secretin).
2. Some GI glands release kinins ( Kallidin, bradykinin) which are powerful vasodilators.
¨ Decrease 02 concentration in gut wall increases intestinal blood flow, increasing adenosine, a well known vasodilator
Countercurrent blood flow mechanism in villi
– Artery and vein in villus lie in close apposition to each other. Much of O2 diffuses out of arterioles directly into adjacent venules without being carried to the tips of villi.
¨ In disease conditions where there is ischemia to the gut, O2 deficit in tips of villi can cause ischemic death of villi leading to decrease absorptive capacity
Nervous Control of Gastrointestinal Blood Flow
¨ Parasympathetic stimulation – increase local blood flow , increase glandular secretion
¨ Sympathetic simulation – intense vasoconstriction of arterioles with decrease blood flow
After few minutes of vasoconstriction, flow often returns to normal, causing return of necessary nutrient blood flow to GI glands and muscles.
IMPORTANCE OF DEPRESSION OF GI BLOOD FLOW
Allows shutting off of GI and splanchnic blood flow for a short time when increase blood is needed to heart and skeletal muscle (exercise), brain and vital organs (circulatory shock).
PROPULSION AND MIXING OF FOOD IN GIT
JOAQUIN A. MORENO, M.D.
DIPLOMATE IN INTERNAL MEDICINE AND GASTROENTEROLOGY
INGESTION OF FOOD
Because digestive enzymes act only on surfaces of food particles, the rate of digestion is dependent on total surface area exposed to digestive secretions.
Grinding of food to very fine consistency prevents excoriation of git, increases ease of gastric emptying.
STAGES OF SWALLOWING
Voluntary – initiates swallowing process
Pharyngeal – involuntary; passage of food thru pharynx into esophagus
Esophageal – involuntary; passage of food from pharynx to stomach
Trachea closed è Esophagus opened è fast peristaltic wave originates in pharynx è Forces bolus of food into upper esophagus
Swallowing center inhibits respiratory center of medulla during pharyngeal stage for less than 2 sec to allow swallowing to proceed.
2 types of peristaltic movements in esophagus
Continuation of peristalsis that begins in pharynx
Lasts 8-10 sec from pharynx to stomach
5-8 sec when in upright position
If primary peristalsis fails to move food into stomach
Results from esophageal distension by retained food
Continue until all food empties into stomach
Receptive relaxation of stomach
Wave of gastric relaxation precedes esophageal peristaltic wave as it passes toward the stomach
Factors that prevent reflux of gastric contents into esophagus
Lower esophageal sphincter (Gastroesophageal Sphincter)
Valve-like closure of lower esophagus
LES – esophageal circular muscle at the lower end of esophagus normally remains constricted
MOTOR FUNCTIONS OF STOMACH
Storage of food until it can be processed in duodenum
Mixing of food with gastric secretions until it becomes semifluid (chyme)
Slow emptying of chyme into SI at a rate suitable for digestion and absorption
Anatomic divisions of stomach
Physiologic divisions of stomach
ORAD PORTION – first two-thirds of body of stomach
CAUDAD PORTION – distal one-third of body and the antrum
BASIC ELECTRICAL RHYTHM OF THE STOMACH
When the stomach contains food, weak peristaltic waves (constrictor or mixing) begin in midportion of stomach toward the antrum once every 15-20 sec.
These constrictor or mixing waves are initiated by gut wall basic electrical rhythm that occur spontaneously in gastric wall
As these waves progress into the antrum from the body of the stomach, they become more intense and powerful, forcing antral contents into a small pyloric opening, which also contracts further, impeding gastric emptying.
Most of antral contents are squeezed upstream toward the gastric body rather than down the pylorus, a process called RETROPULSION, an important mixing mechanism.
Another type of intense contraction when the stomach has been empty for several hours.
Mild pain experienced in the epigastric area when hunger contractions occur.
Begins 12-24 hrs after last meal.
Greatest intensity in 3-4 days then gradually weakens.
EMPTYING THE STOMACH
Pumping action of peristaltic waves aside from causing mixing in the stomach, forcing chyme into duodenum.
Pyloric circular muscle that remains tonically contracted almost all the time, preventing passage of most food until they are almost of fluid consistency.
Nervous and humoral signals from the stomach and duodenum influence the degree of constriction of the pylorus
GASTRIC FACTORS THAT PROMOTE EMPTYING
Hormone released from antral mucosa causing secretion of highly acidic gastric juice.
Has stimulatory effect on motor fxn in gastric body.
Enhance activity of pyloric pump and aids in promoting gastric emptying.
When food enters the duodenum, multiple reflexes are initiated to slow or stop gastric emptying as the volume of chyme in duodenum becomes too much.
These reflexes also inhibit pyloric pump contraction and increase pyloric sphincter tone.
THE POWERFUL DOUDENAL FACTORS THAT INHIBIT STOMACH EMPTYING
Factors that can excite enterogastric reflexes
Degree of duodenal distension.
Irritation of duodenal mucosa.
Degree of acidity of duodenal chime.
Degree of osmolality of chime.
Presence of breakdown products of protein in chime.
Hormonal feedback from duodenum inhibits gastric emptying by inhibiting pyloric pump and increasing strength of pyloric sphincter contraction.
Fats entering the duodenum stimulate production of hormones. CCK is the most potent. Other possible but weak inhibitors of gastric emptying are Secretin and GIP.
SUMMARY OF THE CONTROL OF STOMACH EMPTYING
Feedback mechanisms that slow gastric emptying:
Enterogastric nervous feedback reflexes.
Slow rate of gastric emptying occurs when:
Too much chyme already in SI.
Chyme is very acidic, contains unprocessed protein or fat, hypotonic or hypertonic or when chyme is irritating.
MOVEMENTS OF SI
Mixing contractions (Segmentation Contractions).
Net movement of chyme along SI –
1 cm/min (0.5 – 2 cm/min)
Passage of chyme from pylorus to ileocecal valve – 3-5 hours
Hormones that enhance intestinal motility
Hormones that inhibit si motility
Powerful and rapid peristalsis caused by intense irritation of intestinal mucosa (e.g. infectious diarrhea) which travel long distances in the SI within minutes.
Intensifies peristalsis in ileum immediately after a meal forcing chyme thru ileocecal valve into cecum.
Feedback control of ileocecal sphincter
Whenever the cecum is distended, the contraction of the ileocecal sphincter is intensified and ileal peristalsis is inhibited, delaying emptying of additional chyme from the ileum.
MOVEMENTS OF THE COLON
PRINCIPAL FUNCTIONS OF COLON
Absorption of water and electrolytes from chyme to form solid feces -prox half of colon.
Storage of fecal matter until it can be expelled - distal half.
Mixing movements – combined contractions of circular and longitudinal strips of muscle cause unstimulated portion of colon to bulge outward into baglike sacs (haustrations).
Propulsive movements – “mass movements”.
Modified type of peristalsis where a constrictive ring occurs in response to a distinded or irritated point usually in transverse colon. The 20 cm of colon distal to the constriction contract as a unit forcing fecal material en masse further down colon.
Mass movements can be initiated by
Gastrocolic reflex – distension of stomach
Duodenocolic reflex – distension of duodenum
Feces enter rectum è distension of rectal wall è afferent signals to myenteric plexus è peristaltic wave in desc colon, sigmoid, rectum è int and ext anal sphincter relax
Intrinsic defecation reflex by itself is weak. It needs to be intensified by parasympathetic defecation reflex
AUTONOMIC REFLEXES THAT INHIBIT INTESTINAL ACTIVITY
Peritoneointestinal – irritation of peritoneum causing intestinal paralysis
Renointestinal – kidney irritation
Vesicointestinal – bladder irritation
Somatointestinal – skin over abdomen is irritated
SECRETORY FUNCTIONS OF THE GIT
2 Primary functions of secretory glands
n Secrete digestive enzymes from mouth to terminal ileum
n Provide mucus for lubrication from mouth to anus
Types of Glands
n Mucous cells (Goblet)
– Extrudes mucus for lubrication against mucosal surface excoriation
n Crypts of Lieberkuhn
– Contain specialized secretory cells
n Tubular glands
– Secretes acid and pepsinogen
– Found in stomach and proximal duodenum
n Complex glands
– Provide secretions for digestion and emulsification of food
Types of stimuli that activate enteric nervous system
n Tactile stimuli
n Chemical irritation
n Gut wall distention
n increase rate of alimentary glandular secretion
– Glands of distal portion of large intestine
n Reduces secretions mainly because of vasoconstrictive reduction of blood supply, especially if parasympathetic and humoral stimulation is already increasing increased secretion.
Characteristics of Mucus
n Adheres tightly to food
n Sufficient body to cool gut wall
n Low resistance to slippage
n Causes fecal matter to adhere to one another
n Strongly resistant to digestion by GI enzymes
n Amphoteric – capable of buffering either acid or alkali
Mucus has the ability to allow easy slippage of food along GIT to prevent excoriation or chemical damage to the gut lumen
Glands of Salivation
n Parotid-serous secretions
n Submandibular – both serous and mucus
n Sublingual – both serous and mucus
n Buccal - mucus
Daily secretion of saliva:
> ave 1000ml
2 types of protein secretion of saliva
– Contain ptyalin for digesting starches
– Contains mucin lubrication and surface protection
Function of saliva for oral hygiene
n Wash away bacteria and food particles
n Contains proteolytic enzymes and thiocyanate ions that destroy bacteria
n Contains protein antibodies that destroy bacteria
Salivary glands are controlled mainly by parasympathetic nervous signals from superior and inferior salivary nuclei in brainstem.
Sympathetic stimulation also increases stimulation but much less. Salivation directly dilates BV caused by vasodilator effect of Kallikrein and Bradykinin
Esophageal secretion entirely mucoid to provide lubrication for swallowing, preventing mucosal excoriation of newly entering food in upper esophagus, and protection from digestion of acidic gastric juice at lower esophagus.
Gastric secretion: 2 Types of Glands
n Oxyntic (gastric)
– HCl, pepsinogen, IF, mucus
– Located in body, fundus
– mucus, gastrin, pepsinogen
– located antrum
3 types of cells of Oxyntic gland
n Mucus neck cells
– Mucus, pepsinogen
n Peptic (chief) cells
n Parietal (oxyntic) cells
– HCl, IF
Other enzymes located in the stomach
n Gastric lipase – little importance
n Gastric amylase – minor role
n Gelatinase – liquefy proteoglycans in meat
n IF – absorption of Vit B12 in ileum
Destruction of Parietal cells
n Pernicious anemia
– Failure of RBC maturation due to absence of Vit B12 stimulation of BM
Surface mucus cells
n Found in entire surface of the stomach.
n Secrete very viscid alkaline mucus coating surface with a gel layer >1mm thick, protecting it from highly acid proteolytic gastric secretions as well as for lubricattion.
NT and hormones that directly stimulate gastric gland secretion
n Acetylcholine – secretion of pepsinogen by peptic cells; HCl by parietal cells; mucus by mucus cells
n Histamine – HCl by parietal cells
n Gastrin – HCl by parietal cells
n Parietal cells are the only cells that excrete HCl acid. Enterochromaffin cells which secrete histamine, release them in direct contact with parietal cells of gastric glands. The rate of formation and secretion of HCl by parietal cells is directly related to amount of histamine excreted.
Ways by which Enterochromaffin cells can be stimulated to secrete histamine
– Probably most potent mechanism
– Secreted by G cells (gastrin cells) in antrum in response to protein
n Proteins ® stimulate gastrin cells ® release gastrin into digestive juices ® gastrin transported to chromaffin cells ® histamine release ® stimulate HCl acid secretion
2 type of signals causing Pepsinogen secretion
n Stimulation of Peptic cells by acetylcholine release from vagus nerve or gastric enteric NS
n Stimulation of peptic secretion in response to acid in stomach
n The rate of secretion of pepsinogen, precursor of pepsin that causes protein digestion, is strongly influenced by amount of acid in the stomach
Phases of Gastric Secretion
n Cephalic phase
– Results from sight, smell, thought, or taste of food; accounts for 20% of gastric secretion
n Gastric phase
– Food in stomach excites vasovagal reflexes, local enteric reflexes, gastrin mechanism, all causing secretion; accounts for 70% of gastric secretion.
n Intestinal phase
– Food in proximal SI causes small amounts of gastric secretions because of small amounts of gastrin unbound by duodenal mucosa in response to distention or chemical stimuli.
n Presence of food in SI initiates a severe enterogastric reflex that inhibits gastric secretion. This is initiated by distention of SI, acid in SI, protein breakdown products or mucosal irritation.
n Presence of acid, fat, protein breakdown products, irritation in proximal SI cause release of hormones that inhibit gastric secretion.
(secretin, GIP, VIP, somatostatin)
n Inhibition of gastric secretion by intestinal factors shows release of chyme from stomach when SI is already filled.
Pancreatic secretion contains
n Enzyme for digesting protein, carbohydrate, fats
n HCO3 ions to neutralize acid chyme
n Protein digestion
– Trypsin, chymotrypsin, carboxypolypeptidase, elastase, mucilase
n CHO digestion
n Fat digestion
– Lipase, cholesterol esterase, phospholipase
n These proteolytic enzymes are in inactive forms when first synthesized in pancreatic cells and are activated only after they are secreted into GIT.
Trypsinogen ® activated by enzyme enterokinase ® trypsin
Chymotrypsinogen ® activated by trypsin ® chymotrypsin
n Trypsinogen can be activated by trypsin that has already been formed from trypsinogen.
n Proteolytic enzymes should be activated after they have been secreted into the intestine otherwise they would digest the pancreas itself.
n Trypsin inhibitor promotes activation of trypsin and other enzymes inside the secretory cells and acini and ducts of pancreas.
n Pancreas becomes severely damaged and duct becomes blocked ® large amounts of pancreatic secretion becomes pooled in damaged areas of pancreas ® effect of trypsin inhibitor overwhelmed ® pancreatic secretion rapidly activated ® can digest the pancreas.
Basic stimuli that cause pancreatic secretion
– Released from parasympathetic vagus nerve and other cholinergic nerves, causing production of large amount of pancreatic enzymes.
– Secreted by duodenal and upper jejunal mucosa cause production of large amount of pancreatic enzymes.
n Secretin secreted by duodenal and upper jejunal mucosa stimulates secretion of HCO3 solution.
Importance of Secretin stimulation of HCO3 secretion
n Bicarbonate secretion neutralizes acidic stomach chyme protecting the SI mucosa from digestive action of acid gastric juice.
n Bicarbonate secretion provides approptiate pH for action of pancreatic enzymes.
Functions of Bile
1. Fat digestion because bile acids.
a. Emulsify large fat particles into many minute particles.
b. Aid in absorption of digested fat end-products thru intestinal mucosal membrane.
2. Serves as means of secretion of waste products from the blood.
n Hepatocytes ® bile canaliculi ® interlobular septa ® terminal BD ® hepatic duct ®CBD ® either duodenum or cystic duct then GB.
n A second portion of secretion stimulated by secretin is added to initial bile causing release of increased quantities of HCO3 ions.
n CCK causes GB contraction and relaxation of Sphincter of Oddi, causing GB emptying. Stimulus for CCK secretion is fatty food entering the duodenum.
BILE SALTS HAS 2 IMPT ACTIONS IN GIT
n Emulsifying or detergent function.
n Help in absorption of FA, monoglyceride, cholesterol by forming minute complexes with these lipids called micelles.
ENTEROHEPATIC CIRCULATION OF BILE SALTS
n 94% of bile salts are reabsorbed from SI into blood, enters portal blood to liver. On reaching sinusoids, these salts are absorbed into hepatocytes and are then secreted into bile.
CAUSES OF GALL STONES
n Too much absorption of water from bile
n Too much absorption of bile acids from bile
n Too much cholesterol in bile
n Inflammation of GB epithelium
n BRUNNER’S GLAND – first few cm of duodenum bw pylorus and papilla of Vater; secrete mucus to protect duodenal mucosa from digestion by highly acid gastric juice
n Sympathetic stimulation inhibit Brunner’s gland, leaving duodenal bulb unprotected from highly acid gastric juice causing peptic ulcer.
n Crypts of Lieberkuhn – small pits located over entire surface of SI, lying bw villi
2 CELL TYPES IN CRYPTS
n Goblet cells – secrete mucus that lubricate and protects intestinal surface.
n Enterocytes – secrete water and electrolytes in the crypts and reabsorb water and electrolytes along with end products of digestion.
REGULATION OF SI SECRETION
n Local stimuli – tactile or irritative stimuli initiates local enteric nervous reflexes.
n Hormonal regulation.
n Secretions of large intestine – consists mainly of mucus regulated by direct tactile stimulation and local nervous reflexes.
n Large intestine becomes irritated ® mucosa secretes large quantities of water, electrolytes and mucus ® dilutes the initiating factor ® rapid movement of feces towards anus (diarrhea).
DIGESTION AND ABSORPOTION IN THE GIT
3 Major Sources of CHO in diet:
1. Sucrose – cane sugar; disaccharide
2. Lactose – dissacharide in milk
3. Starches – large polysaccharides in non animal foods and grains
CHO digestion in mouth and stomach
n Chewed food mixed with saliva containing ptyalin à hydrolyzes starch to maltose and small polymers of glucose.
CHO digestion in SI
n Pancreatic amylase is several times more powerful as salivary amylase.
n Almost all starches are converted into maltose and small glucose polymers before passing beyond duodenum and proximal jejunum.
n Once maltose and small glucose polymers reach SI, these disaccharides are split into monosaccharides by enterocytes lining the villi which contain enzyme lactase, sucrase, maltase and a-dextrinase.
n Lactose à broken down into galactose and glucose
n Sucrose à fructose and glucose
n Maltose à glucose
Protein Digestion in Stomach
n Pepsin, the peptic enzyme of the stomach, initiates the process of protein digestion, converting protein into proteoses, peptones and polypeptides.
n For pepsin to cause digestive action on protein, the pH in the stomach should be 2-3, which is the usual pH when the gastric contents mix with HCl.
n Pepsin has the ability to digest collagen, a major constituent of intercellular connective tissue of meat. It is necessary that collagen be digested for the digestive enzymes to digest meat cellular proteins.
Protein digestion by pancreatic enzymes
n Most protein digestion occurs in duodenum and jejunum with the influence of proteolytic pancreatic enzymes.
n Trypsin and chymotrypsin à split protein into small polypeptides
n Carboxypolypeptidase à polypeptides à aa
n Proelastase à elastase à digest elastin of meat fibers
n The last stage of protein digestion occurs in enterocytes lining the SI villi. In the membrane of the microvilli are peptidases (aminopolypeptidases and dipeptidases) which split polypeptides into tri and dipeptides à transported to interior of enterocyte à digested to the final stage of digestion as AA
Digestion of Fats
Fats in the diet composed of:
1. Triclyceride – neutral fat; most abundant
4. Cholesterol esters
n Essentially all the fat digestion occurs in SI. The first step is emulsification of fat, the breakdown of fat globules into small sizes. Bile which contain large quantities of bile salts, and the phospholipid lecithin, are extremely important for fat emulsification.
Digestion of Triglycerides by Pancreatic Lipase
n Pancreatic lipase is the most important enzyme for triglyceride digestion, which splits triglycerides into FFA and monoglycerides.
n Bile salts, when in high concentration, form micelles, which act as a transport medium to carry the monoglyceride and FFA to the brush borders of intestinal epithelial cells where it is absorbed into the blood.
Basic Principles of GI Absorption
n The total quantity of fluid absorbed each day by intestines bw 8-9 liters (1.5 liters from ingested fluid, and 7 liters from GI secretions). All of these are absorbed except for about 1.5 liters which is passed out of the ileocecal valve.
n The stomach has poor absorptive functions because:
1. 1. Lacks the villus type of absorptive membrane
2. Junctions between epithelial cells are tight
n The combination of the Kerckring folds (valvulae conniventes), villi and microvilli increases the absorptive area of the mucosa 1000x.
Basic mechanisms of absorption
n Active transport – needs energy to transport the substance to the other side of the membrane.
n Diffusion – transport of substances thru the membrane as a result of random molecular mov’t.
n Solvent drag – the flow of the solvent as it is absorbed will “drag” dissolved subs along with it.
Absorption of Water
n Water is transported thru intestinal membrane entirely by diffusion.
n When a person becomes dehydrated, large amounts of aldosterone is secreted by adrenal cortex which serves to conserve salt and water in the body.
Absorption of ions
n Sodium – active transport; aldosterone greatly enhances is absorption; ff Na absorption is osmosis of water into paracellular spaces caused by osmotic gradient created by the elevated conc of sodium ion.
n Chloride – absorption occurs by diffusion; Cl ions move along the electrical gradient caused by sodium absorption, thus Cl ions follow the sodium ions.
n Bicarbonate – absorbed in an indirect way by combining with H ions to form carbonic acid (H2CO3) which then dissociates into H20 and CO2. The water remains part of chyme and CO2 is absorbed into bld and expired thru lungs.
n Calcium – actively absorbed from duodenum; parathyroid hormone secreted by parathyroid gland activates Vit D which in turn enhances Ca absorption.
Absorption of Nutrients
n CHO Absorption – essentially all CHO are absorbed in the form of monosaccharides, most abundant of which is glucose (80%). This is because glucose is the final digestion product; remaining 20% is composed of galactose and fructose.
n Glucose is basically transported by a sodium co-transport mechanism. Intestinal glucose combines simultaneously with the same transport protein as sodium and both are transported together to the cell interior.
n Galactose – absorbed same way as glucose.
n Fructose – facilitated diffusion; much of it is converted to glucose on entering the cell
n Most are absorbed thru luminal membranes of intestinal epithelial cells in the form of di- and tripeptides and few free AA. These bind with a specific transport protein that requires sodium binding before transport can occur.
n Digested to form monoglycerides and FFA, both dissolved in central lipid portion of micelles. These are carried to surface of microvilli, and then diffuse immediately from the micelle into the membrane of the microvilli to the interior of the cell.
Absorption in the Colon: Formation of Feces
n About 1.5 liters of chyme pass thru ileocecal valve into the colon. Most are absorbed leaving less than 100 ml of fluyid to be excreted in the feces.
n Most of the absorption occurs in the proximal half of the colon, while storage takes place in the distal half.
n Colon has high capability for active absorption of sodium and the resultant electrical gradient causes chloride absorption as well, at the same time secreting HCO3 to neutralize the acidic end products of bacterial action taking place in the colon. The osmotic gradient caused by Na and Cl ions in turn cause water absorption.
n Maximum absorption capacity of colon – 5-8 liters of fluid and electrolytes per day.
n When total quantity entering the colon exceeds this amount, diarrhea occurs.
Bacterial Action in the Colon
n Digestion of small amounts of cellulose.
n Formation of Vit K, Vit VB12, thiamine, riboflavin and various gases (CO2, H, methane). These gases contribute to formation of flatus.
Composition of Feces
n Water – 75%
n Solid matter – 25%
a) dead bacteria – 30%
b) fat – 10-20%
c) inorganic matter – 10-20%
d) Protein – 2-3%
e) undigested roughage – 30%
n Stercobilin and Urobilin – gives brown color to feces; derivatives of bilirubin
n Stool odor is caused by products of bacterial action (indole, skatole, mercaptans, and hydrogen sulfide).
PHYSIOLOGY OF GI DISORDERS
Disorders of Swallowing and of the Esophagus
n Paralysis of Swallowing Mech – result from damage to 5th, 9th, or 10th CN.
A. Poliomyelitis and Encephalitis – damage to swallowing center in brain stem
B. Muscle Dystrophy – paralysis of swallowing muscles
C. Myasthenia gravis, Botulism – failure of neuromuscular transmission
Abnormalities that can occur when swallowing mech is paralyzed:
n Swallowing cannot occur.
n Food passes into lungs instead of esophagus because of failure of closure of glottis.
n Food refluxes into nose because of failure of soft palate and uvula to close the posterior nares.
Achalasia and Megaesophagus
n Achalasia – LES fails to relax during swallowing, remains spastically contracted; due to damage of myenteric plexus losing its ability to transmit a signal to cause receptive relaxation of LES.
n Megaesophagus – esophagus becomes tremendously enlarged over months or years as a result of achalasia.
Disorders of Stomach
n Gastritis – inflammation of gastric mucosa; may be superficial or deep; chronic gastritis may cause atrophy of gastric mucosa.
n Alcohol and aspirin – most common ingested irritant substances that can damage the protective gastric mucosal barrier.
n Gastric Barrier – causes low level of absorption of food from the stomach directly into the blood
n Features of gastric mucosa causing low level of absorption
A. Highly resistant mucous cells that secrete viscid and adherent mucus.
B. Tight junction between adjacent epithelial cells.
n Achlorhydria – stomach fails to secrete HCl; pH of gastric secretions fails to decrease below 6.5 after max stimulation of acid.
n Hypochlorhydria – diminished acid secretion.
n Both conditions occur as a result of gastric atrophy when there is little or no gastric gland activity.
Pernicious Anemia in Gastric Atrophy
n Parietal cells secrete both HCl and IF, the latter needed for adequate absorption of Vit B12 from ileum. The IF combines with Vit B12 and when this complex reaches ileum, IF binds with receptors in ileal surface making it possible for Vit B12 to be absorbed.
n Aside from chronic gastritis (gastric atrophy), pernicious anemia also occurs in gastric surgery (gastric ulcer or cancer) or when terminal ileum is resected where Vit B12 is entirely absorbed.
n Peptic Ulcer – excoriated area of mucosa caused by digestive action of gastric juice.
n Sites of ulcer:
A. first few cm of duodenum – most freq
B. antrum, lesser curve
C. distal esophagus - rare
D. marginal ulcer – when surgical opening is made between stomach and SI
n Basic Cause of Peptic Ulceration – imbalance between rate of secretion of gastric juice and degree of mucosal protection.
n Peptic ulcer is caused either by:
A. Excess acid and pepsin secretion by gastric mucosa.
B. Diminished ability of gastroduodenal barrier to protect against digestive properties of acid-pepsin complex.
n Bacterial infection by Helicobacter pylori breaks down the gastroduodenal mucosal barrier because of its physical capability to burrow thru the barrier and by releasing bacterial digestive enzymes that liquefy the barrier.
n Factors that Predispose to UlcersL:
A. bacterial infection with H. pylori
B. neurogenic stimulation of excess secretion of gastric juices
C. smoking – inc nervous stimulation of stomach secretory glands
D. alcohol – breaks down mucosal barrier
n Peptic ulcer can be effectively treated by:
A. antibiotics that kill the infectious bacteria
B. acid suppressant drugs
Disorders of Small Intestine
n Lack of pancreatic secretion is caused by:
B. obstruction of pancreatic duct by stone at papilla of Vater
C. removal of pancreatic head because of malignancy
n Loss of pancreatic juice means loss of pancreatic digestive enzymes resulting to malabsorption of fats, protein and CHO, resulting to malnutrition and copious fatty feces.
n Pancreatitis – inflammation of pancreas; either acute or chronic; most common cause is alcohol then obstruction of papilla of Vater by gallstone. Both accounts for 90% of all cases of pancreatitis.
Blockage of papilla of Vater à blocks main secretory duct of pancreas and CBD à pancreatic enzymes dammed up in acini and ducts of pancreas à so much trypsinogen overcomes the Trypsin Inhibitor in secretions à trypsinogen activated to form trypsin à most of proteolytic enzymes becomes activated à digest portions of pancreas
n Sprue – malabsorption caused by dec absorption by the mucosa even thou the food is well digested; can occur when large portions of SI have been removed.
n Nontropical sprue – Idiopathic sprue, celiac disease, gluten enteropathy; results from toxic effects of gluten present in certain types of grains, causing a direct destructive effect on intestinal enterocytes.
n Tropical sprue – believed to be caused by inflammation of intestinal mucosa resulting from unidentified infectious agents.
n Malabsorption in sprue – impairment of fat absorption in early stages; in severe cases, absorption of the other nutrients proteins, CHO, calcium, VitK, folic acid, Vit B12 is impaired
Consequences of severe sprue
n Severe nutritional deficiency – severe body wasting
n Osteomalacia – demineralization of bone from lack of calcium
n Inadequate blood coagulation
n Macrocytic anemia (pernicious anemia type)
Disorders of Large Intestine
n Constipation – slow movement of feces thru LI
a. obstruction to movement of feces – tumors, adhesions
b. irregular bowel habits
c. spasm of small segment of colon
n Megacolon or Hirschsprung’s disease – severe constipation causing the colon to distend to diameters as wide as 3-4 inches resulting from accumulation of large amounts of feces in colon; caused by deficiency of ganglion cells in myenteric plexus.
n Diarrhea – results from rapid movement of fecal matter thru the LI
A. Enteritis – infection in intestinal tract; mucosa becomes irritated, rate of secretion increased, motility is increased.
B. Psychogenic diarrhea – accompanies periods of stress or nervous tension caused by excessive parasympathetic NS.
n Cholera – toxin stimulates excessive fluid and electrolyte secretion from crypts of Lieberkuhn in distal ileum and colon, with amounts as high as 10-12 liters/day
n Ulcerative Colitis – disease where extensive areas of the walls of colon become inflamed and ulcerated; mass movements occur most of the time, causing repeated diarrhea bowel movem ents.
GENERAL DISORDERS OF GIT
n Vomiting – means for upper GIT to rid itself of its contents when it is excessively irritated, overdistended, or overexcitable.
n Antiperistalsis – may begin as far as ileum and travel backward up the intestine at rate of 2-3 cm/sec, which can push up large amounts of intestinal contents all the way to duodenum and stomach w/in 3-5 hrs.
n Events that occur during the act;
A. deep breath
B. rising of hyoid bone and larynx to open UES
C. closing of glottis
D. lifting of soft palate to close posterior nares
E. strong downward contraction of diaphragm
F. simultaneous contraction of abdominal wall muscles
G. g. LES relaxes
H. expulsion of gastric contents upward thru esophagus
n Chemoreceptor Trigger Zone for Vomiting – small area located bilaterally on floor of 4th ventricle of the brain where nervous signals can arise to cause vomiting.
n Drugs like apomorphine, morphine and digitalis can directly stimulate the CTZ and initiate vomiting. Also, stimulation of receptors in vestibular labyrinth in inner ear from rapidly changing direction or rhythm of motion of the body can stimulate the CTZ.
n Nausea – prodrome of vomiting; caused by:
A. irritative impulses coming from GIT
B. impulses originating in lower brain associated with motion sickness
C. Impulses from cerebral cortex to initiate vomiting.
n GI Obstruction
Common Causes are:
B. fibrotic constriction from ulceration or peritoneal adhesions
C. spasm of a gut segment
D. paralysis of a gut segment
n Obstruction causes marked distension of intestine proximal to the obstructed point. Large amounts of fluids and electrolytes continue to be secreted into the lumen but do not increase the rate of absorption because its walls are edematous.
n Prolonged obstruction of LI causes rupture of the intestine, dehydration, circulatory shock.
n Flatus – gases that enter the GIT
3 sources of flatus:
A. swallowed air
B. gases formed from bacterial action
C. gases that diffuse from blood into GIT
n Foods known to cause greater expulsion of flatus: