Med 1B Physiology

Normally, the daily intake of protein (CHON) is 40-50g. In addition to dietary intake of CHON, a large amount of CHON in the form of enzymes, and mucus is also secreted into the gastrointestinal tract or they enter it via the disintegration of epithelial cells of GI tract. Also this CHON is broken down into amino acids and they are absorbed by the small intestine. CHONs are broken down to peptide fragments in the stomach by pepsin and in the small intestine, they are broken down by trypsin and chymotrypsin. These enzymes are secreted by the pancreas. These fragments will be further digested in order to free the amino acids and this digestion is performed again by the carboxypeptidase that is secreted also in the pancreas and by the aminopeptidases that are also secreted in the luminal epithelial membrane of SI. These gastroenzymes are the ones responsible for the splitting of amino acids from the carboxyl and the amino ends of the peptide chains. The free amino acids will then undergo secondary active transport together with sodium across the intestinal wall. Short chains of the 2-3 amino acids are also actively absorbed. This is in contrast to CHO absorption in which the disaccharides are absorbed but in the case of amino acids, 2 or 3 chains of a.a. are absorbed. Like the absorption of CHO, the absorption and digestion of CHON are largely completed in the proximal or early portion of SI. There are small amounts of undigested CHON that are able to cross the intestinal epithelium and to gain access in the interstitial fluid. They do so by the combination of endocytosis and exocytosis. The absorptive capacity for CHON is much greater in infants than adults and the antibodies that are involved in physiological defense system of the body are secreted in the mothers milk and they are immediately absorbed by the infants. So this provides some immunity until the infant can produce its own antibodies.

FAT Fat intake ranges from 25-160g per day. Most of these fats are in the form of triacetylglycerol. The digestion of fat occurs almost and entirely in the small intestine. The major digestive enzyme in the process is pancreatic lipase which catalyzes the splitting of bonds linking fatty acids to the first and 3rd carbon atoms of the glycerol thus producing 2 free fatty acids and a monoglyceride as its product from the triacetylglycerol. The lipase splits the two fatty acid molecules leaving a monoglyceride. Triacyglycerol therefore, will produce 2 fatty acids and monoglyceride. The triacetylglycerol that enters the SI from stomach are insoluble to water are aggregated into large lipid fragments. Since only the lipids at the surface of the droplets are accessible to the water soluble lipase, this digestion could proceed very slowly without the action of bile. Furthermore, the product of lipase activity, these are the fatty acids and the monoglyceride are also insoluble in water. So this fragment of fat digestion is circumvented by the bile salts. It increases the rate of fat digestion and absorption in 2 ways. First, by a process known as emulsification. By this process, they prevent large lipid fragments from aggregating into still larger ones. Then the other way is that they combine with the fatty acids and the monoglycerides that is produced by the digestion of lipase at the droplet surface in order to form small water soluble aggregates which we call ____. In the absence of bile salts, there will be no micelle formation so fat digestion and absorption will occur very very slowly and so much of the ingested fat passes off to the large intestine and it is excreted. Bile salts are formed in the liver using cholesterol as source and are amphipatic (with polar and nonpolar surface) molecules. Mechanical agitation at the intestine will break up the large fat lobules and the resulting droplets become coated with bile salts. Because of the negative charge on the bile salts at the surface, the droplets repel each other and so they do not aggregate. The resulting suspension of the lipid droplet is usually about 1 millimicron in diameter. Its now knows as an emulsion. Although digestion is speeded up by emulsification, absorption of the insoluble products of lipase would be very slow if it were not for the second action of the bile salts, which is the formation of the micelles. These are similar in structure to the emulsion droplets but are not so much smaller. The micelle consists of bile salts, bile acids, monoglycerides, and phospholipase. An oral cholesterol together with the polar ? of each molecule oriented towards the micelles surface. And the nonpolar surface of the amphipatic molecules form the micelles core. Although the monoglycerides and fatty acids enter the epithelial cells from the intestinal lumen, it is the triacetylglycerol that is released on the other side of the cell into the interstitial fluid, thus, during this passage to the epithelial cells, the fatty acids and the monoglycerides are resensitized into triacetylglycerols and this occurs in the agranular endoplasmic reticulum where the enzymes for this triacylglycerol synthesis are located. Within the organelles of the cells, the resensitized fat again aggregate into small droplets that are coated with an amphipatic CHON that performs an emulsifying function similar to that performed by the bile salts. The exit of these fat droplets in the cells will follow the same pathway as that of the secreted CHON. Vesicles containing the droplets will pinch off in the ER and they are processed to the GA and they eventually fuse with the plasma membrane releasing the fat droplets into the interstitial fluid. These small extracellular fat droplets are known as chylomicrons. These chylomicrons contain, in addition to the triacylglycerol, they also contain other lipids including the phospholipids, cholesterol and the fat soluble vitamins. This other lipids have been absorbed by the process wherein fat and monoglycerides have been absorbed. These chylomicrons then pass into the lacteals of the small intestinal lining. They enter into the lacteals, not into the capillaries. The chylomicrons cannot enter in the chylomicrons because of the basement membrane. This is an extracellular polysaccharide of the cell at the other surface of the capillary. This produces a

Med 1B Physiology
barrier to the relatively large chylomicrons. They are absorbed into the lacteals because the lacteals do not have basement membrane. And so these chylomicrons can pass through the lacteals and go to the lymphs, then from lymphs, they ultimately empty in the systemic veins. Vitamins Most vitamins undergo little enzymatic modification during their digestion. Digestion releases the vitamins from the food particles, transferring them into insoluble form in which they can be absorbed (ADEK: fat soluble vit). They follow the pathway that is followed by the digestion and absorption of fats. They are solubilised in the micelle thus any interference with regards to the secretion of bile will also decrease the absorption of these fat soluble vitamins. Most water soluble vitamins are absorbed by diffusion or by means of carrier-mediated transport. However, Vitamin B12, it is a very large and a charged molecule. In order for it to be absorbed, it has to bind with a CHON, aka the intrinsic factor. This intrinsic factor is secreted by the acid-secreting cells of the stomach. The binding of B12 to the intrinsic factor will result into a complex molecule that will bind to the specific site on the epithelial cells in the lower portion of the ileum where the absorption of vit B12 takes place. Vit B12 is required for erythrocytic formation and therefore for the prevention of anemia. So, this form of anemia may occur when the stomach has been removed, for example in gastric ulcers, or the stomach fails to secrete the intrinsic factor. If the absorption of Vit B12 occurs in the lower portion of ileum, removal also of this segment of SI can also cause anemia.

Absorption of Water and Minerals Water is the most abundant substance that is present on chime. Approximately 9L of both the secreted and ingested fluid enters the SI, but only ~500mL or 1/2L will pass on to the large intestine because 95% of the fluid will be absorbed in the small intestine. The epithelial membranes are very permeable to water. Therefore, net water diffusion occurs across the epithelium whenever the water concentration difference is established by means of the active transport of sodium. Sodium ions accounts for most of active transports for solute because they constitute the most abundant solutes in the chyme. Sodium absorption is a primary active transport using the Na-K ATPase pump. The other minerals that are present in small amounts are K, Mg, Ca and they are also absorbed as trace elements like the iron, zinc and iodine.

Absorption of Iron Only about 10% of the ingested iron is ingested into the blood each day. The ions of iron are actively transported into the intestinal epithelial cells where most of them are incorporated to the CHON iron complex aka ferritin. This ferritin acts as the intracellular storage for iron. The absorbed iron that does not bind to the ferritin is released on the blood site and it is passed through plasma CHON and this forms the transferrin and it is in this form that the Fe circulates throughout the body. Most of the Fe bound to ferritin will be released back into the intestinal lumen. When the intestinal cells will disintegrate, the Fe that is bound to this ferritin will be released back into the intestinal lumen. Iron absorption depends on the bodys iron content so when the bodys stores are increased, the amount of Fe that is bound to ferritin is also increased and this can reduce the amount of iron that is released in the blood. When the body stores drop, example when there is loss of Hb during hemorrhage, the amount of Fe that is bound to intestinal ferritin also decreases and this increases the amount of iron that is released in the blood. This is the feedback mechanism of Fe absorption. Iron absorption also depends on the food that we take. This is because Fe binds to negatively charged ions in the food, and this can slow its absorption. For example, the Fe that is ingested when we eat liver, is much more absorbable that the Fe that is in the egg yolk since the latter contain phosphates that bind to the Fe that forms an insoluble complex. The absorption of Fe is typical like most of the other trace metals in several respects. First the several storage CHONs and the plasma carrier CHONs are involved in the absorption of Fe and the other trace elements and the second is the control of absorption. This is the major mechanism for chemiostatic control of bodys content for these trace elements. Regulation of the GI Processes A. Basic principle The GIT reflexes are initiated by a relatively small number of luminal stimuli: 1. Distention of the Wall of the Intestines by the luminal contents 2. Osmolality of the chyme. This means the total [Na] of chyme . 3. Acidity of the Chyme 4. Concentration of specific digestion contents

These stimuli act on the receptors which are located in the walls of the intestinal tract which may be in the form of mechanoreceptors, phosphoreceptors, and chemoreceptors that influence the effectors in the muscle layers and walls of the intestinal tract and also the exocrine glands that secrete substances or enzymes into the lumen of the GIT.

Med 1B Physiology
Neural Regulation of GIT Processes GIT has its own local nervous system which is called the enteric nervous system. These are in the form of 2 nerve networks which are the myenteric plexus and the submucous plexus. These 2 neurons will either synapse with other neurons or they end near the smooth muscles and glands. Many axons of these nerves leave the submucous plexus and vice versa. So the neural activity in one plexus influences also the activity in the other plexus and the stimulus at one point in the plexus can lead to impulses that are conducted both up and down the 2 plexuses. Thus stimuli in the upper part of the SI may affect smooth muscles and glands in the stomach as well as in the lower part of the intestinal tract. Many of these receptors are in fact part of the myenteric and submucous plexus. Nerve fibers for both the sympathetic and parasympathetic branches of the ANS enter this intestinal tract and they synapse with the neurons in both plexuses. So via these pathways, the CNS can influence motor, the secretory activity of the GIT. In addition, there are intra, aka intratract neural plexus that are independent of the CNS, thus two types of neurons or reflex archs are present in the GIT. They are called the short reflexes and the long reflexes. These short reflexes are from receptors through the nerve plexuses and they go directly into the effector cells of the GI tract. The long reflexes act on receptors also of the GIT but they go to the CNS by way of the afferent nerves and then they go back to the nerve plexuses and to the effector cells by way of autonomic nerve fibers for which a longer pathway so they call it a long reflex. Some control for these reflexes are mediated solely by short reflexes or by long reflexes and in others, they are controlled by both. Not all neural reflexes are associated by signals within the GIT. For example, the sight or the smell of food and emotional state of the individual can have significant effect on the GIT and they are mediated through the CNS via the autonomic neurons. Hormonal Regulation of GIT Processes The hormones that control the GIT are secreted mainly by the endocrine cells which are scattered throughout the epithelium of the stomach or SI, and these cells are not clustered into strict organs, like for example the thyroid. They are scattered throughout the epithelium of the stomach and SI. One surface of this endocrine cell is exposed to the lumen of the GIT and it is at this surface that various chemical substances behind will stimulate the cell to release its hormones from the opposite side of the cell which is the blood side. Although some of these hormones can also be detected in the lumen and therefore they actively acting locally as indication of the pathways to glands but most of the hormones in the GIT reach the target cell via the secretion. Several substances are currently investigated as possibly GI hormones but there are only 4 of them that have met the criteria to be called as hormones. These four hormones that have the right to be called hormones are the secretin, cholecystokinin, gastrin and the glucose insulinotrophic peptide or the GIP. Each of these hormones participate in the feedback control that regulates some aspects of the luminal environment and each hormone also affect more than one type of gastric cells. So these 2 generalizations on the hormonal control of GIT can be illustrated by the cholecystokinin. It was said that the presence of fatty acids in the small intestine will trigger the CCK secretion from the duodenum into the blood and this circulating CCK will then stimulate the secretion for the pancreas of digestive enzymes which include lipase that will digest the fat. CCK also causes the gallbladder to contract thus delivering into the SI the bile salts that is required for fat digestion and absorption and as fat is digested and absorbed, the stimulus (the fatty acid in the lumen) for the CCK release will be removed, so the CCK secretion will be stopped. In many cases, a single effector cell contains receptors for more than 1 hormone as well also as receptors for neurotransmitters and ____, and so the result is that there is a variety of inputs that can affect the response of the cells. One example of this interruption is that of a phenomenon aka condensation. CCK stimulates the pancreatic enzyme secretion whereas the hormone secretin is a weaker stimulus for enzyme secretion so in the presence of secretin, CCK stimulates the secretion of the pancreatic enzyme more strongly than would be predicted by the sum of the individual stimulatory effect of CCK and secretin. This is called the condensation. So secretin potentiates the effect of CCK and one of the consequences of condensations is that small changes in the gastro concentration of the particular hormone can have a considerable effect on the action of the other hormones of GIT. In addition to this stimulus to the effector cells, in some cases it cannot be a stimulus but an inhibition, so in addition to this stimulus or inhibition on the effector cell functions, the GI hormones also have tropic effect on various tissues. This includes the gastric and intestinal mucosa and the exocrine portion of the pancreas.

Phases of GIT Control The neural and hormonal control of the GI system is divisible onto three phases: the cephalic, gastric and the intestinal phase. The phases depend according to the stimulus location. In the cephalic phase, this is initiated when the receptors in the head are stimulated by sight, taste, smell, by chewing, as well as other various states. The efferent pathways for these reflexes are parasympathetic, most of which are in the vagus nerve and also sympathetic fibers. These fibers activate neurons in the GI nerve plexuses which in turn affect the secretory and contractile activity of the GIT. The second phase is the gastric phase. It is called gastric because its the stomach stimulus. There are 3 stimuli in the stomach that initiates the reflexes that constitute the gastric phase of this regulation. They are the distention, ?5045 and the peptides that are formed during digestion of the ingested CHONs. And the receptors of these stimuli are mediated by both the short and the long neuron reflexes and by the gastric release. The third phase is the intestinal phase. This is initiated by stimuli in the intestinal tract and they are also distention, the high acidity of the chyme, the osmolality and also the various digestive products. Like the gastric

Med 1B Physiology
phase, the intestinal phase is mediated by both the long and the short neuron reflexes and the GI hormone. In this intestinal phase, the hormones that are involved are the secretin, CCK, and GIP. So, to summarize the properties of these GI hormones:

1. Gastrin: the structure of gastrin: peptide location of the cells that secrete it: antrum of the stomach stimuli for the release of this hormone: amino acids, the peptides in the stomach, the parasympathetic nerves stimuli for the inhibition of this hormone: acid in stomach 2. CCK: it is a peptide location of the cells that secrete it: SI stimuli for secretion: amino acids and the fatty acids in the SI no stimuli for inhibition of CCK. 3. Secretin: also a peptide location: SI stimulus for secretion: acids of the SI no stimuli for inhibition 4. Glucose insulinotrophic peptide: location: SI stimuli for secretion: glucose and fat in the SI no stimulus for inhibition The target cell responses to these hormones: Stomach: acid secretion - stimulated by gastrin - inhibited by secretin Antrum contraction - stimulated by gastrin - inhibited by secretin Pancreas: bicarbonate secretion - the CCK potentiates the action of secretin and secretin stimulates also the secretion of the bicarbonate enzyme secretion - stimulated by CCK and secretin potentiates the action of CCK insulin secretion - GIP stimulates it Liver: bicarbonate secretion - the CCK potentiates secretin action and secretin stimulates secretion Gallbladder: contraction - stimulated by CCK for sphincter of Odde - CCK relaxes this sphincter SI motility: gastrin stimulates the ileum, but it inhibits the ileocaecal sphincter LI motility: gastrin is the one that stimulates the mass action of LI For the growth of the epithelial cells, gastrin stimulates this in the stomach and small intestinal mucosa. CCK also stimulates the secretion of the pancreatic cells specially the exocrine pancreatic cells growth Secretin stimulates the exocrine pancreatic growth

There are specific contractile and secretory processes that occur in each segment of the GI system. Those that happen in the mouth, pharynx, esophagus and the most important here is the chewing and secretion of saliva, and swallowing. Chewing is controlled by the somatic nerves in the skeletal muscles in the mouth and the jaw and in addition to the voluntary control of the muscle, rhythmic chewing motions are also reflexly activated by the pressure of food against the gums, hard palate and tongue, and the activation of these mechanoreceptors would lead to reflexive inhibition of the muscles that hold the jaw closed. The resulting relaxation of these jaw muscles will also reduce the pressure that will lead to a new cycle of

Med 1B Physiology
contraction and relaxation of this muscle. Although the chewing prolongs the subjective pleasure of taste, it does not alter the rate at which the food will be digested and absorbed from the SI. On the other hand, if you swallow a large particle of food without chewing, then it can lead to choking if the particle lodges over the trachea, blocking the passage of air into the lungs. Saliva-secreted by three pairs of exocrine glands: the parotid, submandibular and sublingual. The major salivary CHONs are the enzyme amylase and the mucin. This will mix with water to form a highly viscous solution, aka the mucous. This secretion of saliva is controlled by both parasympathetic and sympathetic neurons. Unlike their antagonistic activity in most organs, both systems stimulate salivary secretion, but the parasympathetic produces a greater response. In the absence of an ingested food, there is a low rate of salivary secretion. The secreted amount of saliva is just enough to keep the mouth moist, but in the presence of food, the salivary secretion increases markedly and this is a reflex. The reflex response is initiated by chemoreceptors and pressure receptors in the wall of the mouth and in the tongue. Swallowing- a complex reflex that is initiated when the pressure receptors in the walls of the pharynx are stimulated by food or drink that is forced into the rear end of the mouth by the tongue. These receptors send afferent impulses to the swallowing center in the brainstem and medulla which coordinates the swallowing process via an efferent fiber to the muscle of the pharynx, larynx, and esophagus as well as the muscle in the respiratory system. And so as the ingested food moves to the pharynx, the soft palate is elevated and it plunges against the back wall of the pharynx. This will prevent the food from entering to the nasal cavity. Impulses from the swallowing center will inhibit respiration. As the tongue forces the food further back into the pharynx, the food will tilt a flat tissue which is called the epiglottis. It will tilt backward in order to close the glottis. And the next therefore is the swallowing which occurs in the esophagus. The skeletal muscles surrounding the upper third of esophagus will contract as well as the smooth muscles of the lower 2/3 of the esophagus. The pressure in the thoracic cavity is 4-10mm Hg less than the atmospheric pressure and this subatmospheric pressure is transmitted across the wall of the esophagus into the lumen. In contrast, the pressure in the lumen at the beginning of the esophagus is equal to the atmospheric pressure and the pressure at the opposite end of the esophagus in the stomach is slightly greater than the atmospheric pressure. So this pressure differences would tend to force the air from above and the stomach content from below into the esophagus but this does not happen because both ends of the esophagus are normally closed by sphincter muscles. The skeletal muscles surrounding the esophagus just below the pharynx will form the upper esophageal sphincter whereas the smooth muscles in the last portion of the esophagus will form the lower esophageal sphincter. So the esophageal phase of swallowing begins with the relaxation of the upper esophageal sphincter. Immediately after the food has passed, the sphincter will now close again and the glottis opens and breathing proceeds. Once in the esophagus, the food is moved towards the stomach by means of a progressive wave of muscle contractions that proceeds along the esophagus. This compresses the lumen and forces the food. Such waves of contraction in the muscle layers surrounding the tube is called peristaltic wave. One esophageal peristaltic wave takes about 5 seconds to reach the stomach. Swallowing can occur even when a person is upside down because it is not dependent with gravity. The lower esophageal sphincter will now again open and remains relaxed throughout the period of swallowing thus allowing the food to enter the stomach. When the food has passed, the sphincter closes again and thus receiving the junction of esophagus and stomach. So swallowing is an example of reflex in which multiple responses in the temporal sequence that is determined by the pattern of this synaptic connections between the neurons in the coordinate center .So since both the skeletal and smooth muscles are involved, the swallowing center must direct the efferent activity in both the somatic nerves and into the skeletal muscles and to the autonomic nerves specifically the parasympathetic fibers going to the smooth muscles. Simultaneous afferent fibers of the receptors of the esophagus will send the swallowing center information that can alter the activity. For example, if a large food particle does not reach the stomach during the initial peristaltic wave, the distention of the esophagus by the particle will activate receptors that initiate reflexes causing repeated waves of peristaltic activity. This is called secondary peristalsis. Now the ability of the lower esophageal sphincter in maintaining the barrier between the stomach and the esophagus is ? by the fact that the last portion of the esophagus lies below the diaphragm and therefore subject to abdominal pressure.