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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 wil l 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, theresensitized 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


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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 areabsorbed 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. Sodiumions 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 Chyme4. 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.


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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 enterthis 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 arescattered 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


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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 nervesstimuli 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 SIno 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 CCKinsulin 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 m uscles 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


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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 greaterresponse. 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 thissubatmospheric 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. Soswallowing 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.

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